bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resolving the High‐Latitude Ionospheric Irregularity Spectra Using Multi‐Point Incoherent Scatter Radar Measurements
Authors: Goodwin L. V. , Perry G. W. 
Published: August 2022

AbstractTo provide new insights into the relationship between geomagnetic conditions and plasma irregularity scale‐sizes, high‐latitude irregularity spectra are computed using a novel Incoherent Scatter Radar (ISR) technique. This new technique leverages: (a) the ability of phased array Advanced Modular ISR (AMISR) technology to collect volumetric measurements of plasma density, (b) the slow F‐region cross‐field plasma diffusion at scales greater than 10 km, and (c) the high dip angle of geomagnetic field lines at high‐latitudes. The resulting irregularity spectra are of a higher spatiotemporal resolution than what has been previously possible with ISRs. Spatial structures as small as 20 km are resolved in less than 2 minutes (depending on the radar mode). In this work, we focus on Resolute Bay ISR‐North (RISR‐N) observations operating in the “imaginglptight” mode. In addition to having an unprecedented view of the size and occurrence of irregularities as they traverse the polar cap, we find that as the F‐region plasma density decreases below approximately 2.5 × 1010 m−3 at 350 km altitude the spectral power shifts to scale‐sizes lower than 50 km. Additionally, near magnetic local noon, the spectral power shifts to scales greater than 50 km, and from 15 to 6 magnetic local time, the spectral power shifts to scales lower than 50 km. This reflects the role of photoionization dominating high‐latitude ionospheric structuring in the polar cap.
Diltiazem inhibits breast cancer metastasis via mediating growth differentiation factor 15 and epithelial-mesenchymal transition
Authors: Chen Yen-Chang , Wu Chen-Teng , Chen Jia-Hong , Tsai Cheng-Fang , Wu Chen-Yun , Chang Pei-Chun , Yeh Wei-Lan 
Published: August 2022

AbstractMigration and metastasis commonly happen to triple-negative breast cancer (TNBC) patients with advanced diseases. In many studies, it has been suggested that epithelial-mesenchymal transition (EMT) is one of the key mechanisms triggering cancer metastasis. Accumulating evidence has proven that calcium channel blockers mediate cell motility. Therefore, we attempt to investigate the effects of diltiazem, which has been selected from several FDA-approved clinical calcium channel blockers, on EMT in TNBC. By using both mouse and human TNBC cell lines, we found that diltiazem decreases colony formation and cell migration in breast cancer cells. The expression of epithelial markers such as E-cadherin and ZO-1 were increased dose-dependently by diltiazem, while mesenchymal markers such as Snail and Twist were decreased. In addition, we found that the expression of growth differentiation factor-15 (GDF-15) was also increased by diltiazem. Administering recombinant GDF-15 also reverses EMT, inhibits colony formation and migration in breast cancer cells. Moreover, treatment with diltiazem in tumor-bearing mice also decreases cancer metastasis and nodule formation, with more GDF-15 expression in diltiazem-treated mice than saline-treated mice, respectively. These findings suggest that diltiazem regulates EMT and cell motility through elevating GDF-15 expression in breast cancers in vitro and in vivo.
Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH)
Authors: Xu Xiaohan , Poulsen Kyle L. , Wu Lijuan , Liu Shan , Miyata Tatsunori , Song Qiaoling , Wei Qingda , Zhao Chenyang , Lin Chunhua , Yang Jinbo 
Published: August 2022

AbstractNon-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH) has become the leading cause of liver disease worldwide. NASH, an advanced form of NAFL, can be progressive and more susceptible to developing cirrhosis and hepatocellular carcinoma. Currently, lifestyle interventions are the most essential and effective strategies for preventing and controlling NAFL without the development of fibrosis. While there are still limited appropriate drugs specifically to treat NAFL/NASH, growing progress is being seen in elucidating the pathogenesis and identifying therapeutic targets. In this review, we discussed recent developments in etiology and prospective therapeutic targets, as well as pharmacological candidates in pre/clinical trials and patents, with a focus on diabetes, hepatic lipid metabolism, inflammation, and fibrosis. Importantly, growing evidence elucidates that the disruption of the gut–liver axis and microbe-derived metabolites drive the pathogenesis of NAFL/NASH. Extracellular vesicles (EVs) act as a signaling mediator, resulting in lipid accumulation, macrophage and hepatic stellate cell activation, further promoting inflammation and liver fibrosis progression during the development of NAFL/NASH. Targeting gut microbiota or EVs may serve as new strategies for the treatment of NAFL/NASH. Finally, other mechanisms, such as cell therapy and genetic approaches, also have enormous therapeutic potential. Incorporating drugs with different mechanisms and personalized medicine may improve the efficacy to better benefit patients with NAFL/NASH.
The dual action of glioma-derived exosomes on neuronal activity: synchronization and disruption of synchrony
Authors: Spelat Renza , Jihua Nie , Sánchez Triviño Cesar Adolfo , Pifferi Simone , Pozzi Diletta , Manzati Matteo , Mortal Simone , Schiavo Irene , Spada Federica , Zanchetta Melania Eva , Ius Tamara , Manini Ivana , Rolle Irene Giulia , Parisse Pietro , Millán Ana P. , Bianconi Ginestra , Cesca Fabrizia , Giugliano Michele , Menini Anna , Cesselli Daniela , Skrap Miran , Torre Vincent 
Published: August 2022

AbstractSeizures represent a frequent symptom in gliomas and significantly impact patient morbidity and quality of life. Although the pathogenesis of tumor-related seizures is not fully understood, accumulating evidence indicates a key role of the peritumoral microenvironment. Brain cancer cells interact with neurons by forming synapses with them and by releasing exosomes, cytokines, and other small molecules. Strong interactions among neurons often lead to the synchronization of their activity. In this paper, we used an in vitro model to investigate the role of exosomes released by glioma cell lines and by patient-derived glioma stem cells (GSCs). The addition of exosomes released by U87 glioma cells to neuronal cultures at day in vitro (DIV) 4, when neurons are not yet synchronous, induces synchronization. At DIV 7–12 neurons become highly synchronous, and the addition of the same exosomes disrupts synchrony. By combining Ca2+ imaging, electrical recordings from single neurons with patch-clamp electrodes, substrate-integrated microelectrode arrays, and immunohistochemistry, we show that synchronization and de-synchronization are caused by the combined effect of (i) the formation of new neuronal branches, associated with a higher expression of Arp3, (ii) the modification of synaptic efficiency, and (iii) a direct action of exosomes on the electrical properties of neurons, more evident at DIV 7–12 when the threshold for spike initiation is significantly reduced. At DIV 7–12 exosomes also selectively boost glutamatergic signaling by increasing the number of excitatory synapses. Remarkably, de-synchronization was also observed with exosomes released by glioma-associated stem cells (GASCs) from patients with low-grade glioma but not from patients with high-grade glioma, where a more variable outcome was observed. These results show that exosomes released from glioma modify the electrical properties of neuronal networks and that de-synchronization caused by exosomes from low-grade glioma can contribute to the neurological pathologies of patients with brain cancers.
Elucidation of an mTORC2-PKC-NRF2 pathway that sustains the ATF4 stress response and identification of Sirt5 as a key ATF4 effector
Authors: Li Ruizhi , Wilson Kristin F. , Cerione Richard A. 
Published: August 2022

AbstractProliferating cancer cells are dependent on glutamine metabolism for survival when challenged with oxidative stresses caused by reactive oxygen species, hypoxia, nutrient deprivation and matrix detachment. ATF4, a key stress responsive transcription factor, is essential for cancer cells to sustain glutamine metabolism when challenged with these various types of stress. While it is well documented how the ATF4 transcript is translated into protein as a stress response, an important question concerns how the ATF4 message levels are sustained to enable cancer cells to survive the challenges of nutrient deprivation and damaging reactive oxygen species. Here, we now identify the pathway in triple negative breast cancer cells that provides a sustained ATF4 response and enables their survival when encountering these challenges. This signaling pathway starts with mTORC2, which upon sensing cellular stresses arising from glutamine deprivation or an acute inhibition of glutamine metabolism, initiates a cascade of events that triggers an increase in ATF4 transcription. Surprisingly, this signaling pathway is not dependent on AKT activation, but rather requires the mTORC2 target, PKC, which activates the transcription factor Nrf2 that then induces ATF4 expression. Additionally, we identify a sirtuin family member, the NAD+-dependent de-succinylase Sirt5, as a key transcriptional target for ATF4 that promotes cancer cell survival during metabolic stress. Sirt5 plays fundamental roles in supporting cancer cell metabolism by regulating various enzymatic activities and by protecting an enzyme essential for glutaminolysis, glutaminase C (GAC), from degradation. We demonstrate that ectopic expression of Sirt5 compensates for knockdowns of ATF4 in cells exposed to glutamine deprivation-induced stress. These findings provide important new insights into the signaling cues that lead to sustained ATF4 expression as a general stress-induced regulator of glutamine metabolism, as well as highlight Sirt5 an essential effector of the ATF4 response to metabolic stress.
XPC–PARP complexes engage the chromatin remodeler ALC1 to catalyze global genome DNA damage repair
Authors: Blessing Charlotte , Apelt Katja , van den Heuvel Diana , Gonzalez-Leal Claudia , Rother Magdalena B. , van der Woude Melanie , González-Prieto Román , Yifrach Adi , Parnas Avital , Shah Rashmi G. , Kuo Tia Tyrsett , Boer Daphne E. C. , Cai Jin , Kragten Angela , Kim Hyun-Suk , Schärer Orlando D. , Vertegaal Alfred C. O. , Shah Girish M. , Adar Sheera , Lans Hannes , van Attikum Haico , Ladurner Andreas G. , Luijsterburg Martijn S. 
Published: August 2022

AbstractCells employ global genome nucleotide excision repair (GGR) to eliminate a broad spectrum of DNA lesions, including those induced by UV light. The lesion-recognition factor XPC initiates repair of helix-destabilizing DNA lesions, but binds poorly to lesions such as CPDs that do not destabilize DNA. How difficult-to-repair lesions are detected in chromatin is unknown. Here, we identify the poly-(ADP-ribose) polymerases PARP1 and PARP2 as constitutive interactors of XPC. Their interaction results in the XPC-stimulated synthesis of poly-(ADP-ribose) (PAR) by PARP1 at UV lesions, which in turn enables the recruitment and activation of the PAR-regulated chromatin remodeler ALC1. PARP2, on the other hand, modulates the retention of ALC1 at DNA damage sites. Notably, ALC1 mediates chromatin expansion at UV-induced DNA lesions, leading to the timely clearing of CPD lesions. Thus, we reveal how chromatin containing difficult-to-repair DNA lesions is primed for repair, providing insight into mechanisms of chromatin plasticity during GGR.
Imbibition-induced selective wetting of liquid metal
Authors: Kim Ji-Hye , Kim Sooyoung , Kim Hyeonjin , Wooh Sanghyuk , Cho Jiung , Dickey Michael D. , So Ju-Hee , Koo Hyung-Jun 
Published: August 2022

AbstractHerein, we present the imbibition-induced, spontaneous, and selective wetting characteristics of gallium-based liquid metal alloys on a metallized surface with micro-scale topographical features. Gallium-based liquid metal alloys are fascinating materials that have enormous surface tension; therefore, they are difficult to pattern into films. The complete wetting of eutectic alloy of gallium and indium is realized on microstructured copper surfaces in the presence of HCl vapor, which removes the native oxide from the liquid metal alloy. This wetting is numerically explained based on the Wenzel’s model and imbibition process, revealing that the dimensions of the microstructures are critical for effective imbibition-driven wetting of the liquid metal. Further, we demonstrate that the spontaneous wetting of the liquid metal can be directed selectively along the microstructured region on the metallic surface to create patterns. This simple process enables the uniform coating and patterning of the liquid metal over large areas without an external force or complex processing. We demonstrate that the liquid metal-patterned substrates maintain electrical connection even in a stretched state and after repetitive stretching cycles.
Rapid evolution of mutation rate and spectrum in response to environmental and population-genetic challenges
Authors: Wei Wen , Ho Wei-Chin , Behringer Megan G. , Miller Samuel F. , Bcharah George , Lynch Michael 
Published: August 2022

AbstractEcological and demographic factors can significantly shape the evolution of microbial populations both directly and indirectly, as when changes in the effective population size affect the efficiency of natural selection on the mutation rate. However, it remains unclear how rapidly the mutation-rate responds evolutionarily to the entanglement of ecological and population-genetic factors over time. Here, we directly assess the mutation rate and spectrum of Escherichia coli clones isolated from populations evolving in response to 1000 days of different transfer volumes and resource-replenishment intervals. The evolution of mutation rates proceeded rapidly in response to demographic and/or environmental changes, with substantial bidirectional shifts observed as early as 59 generations. These results highlight the remarkable rapidity by which mutation rates are shaped in asexual lineages in response to environmental and population-genetic forces, and are broadly consistent with the drift-barrier hypothesis for the evolution of mutation rates, while also highlighting situations in which mutator genotypes may be promoted by positive selection.
Anionic nanoplastic exposure induces endothelial leakiness
Authors: Wei Wei , Li Yuhuan , Lee Myeongsang , Andrikopoulos Nicholas , Lin Sijie , Chen Chunying , Leong David Tai , Ding Feng , Song Yang , Ke Pu Chun 
Published: August 2022

AbstractThe global-scale production of plastics has been instrumental in advancing modern society, while the rising accumulation of plastics in landfills, oceans, and anything in between has become a major stressor on environmental sustainability, climate, and, potentially, human health. While mechanical and chemical forces of man and nature can eventually break down or recycle plastics, our understanding of the biological fingerprints of plastics, especially of nanoplastics, remains poor. Here we report on a phenomenon associated with the nanoplastic forms of anionic polystyrene and poly(methyl methacrylate), where their introduction disrupted the vascular endothelial cadherin junctions in a dose-dependent manner, as revealed by confocal fluorescence microscopy, signaling pathways, molecular dynamics simulations, as well as ex vivo and in vivo assays with animal model systems. Collectively, our results implicated nanoplastics-induced vasculature permeability as primarily biophysical-biochemical in nature, uncorrelated with cytotoxic events such as reactive oxygen species production, autophagy, and apoptosis. This uncovered route of paracellular transport has opened up vast avenues for investigating the behaviour and biological effects of nanoplastics, which may offer crucial insights for guiding innovations towards a sustainable plastics industry and environmental remediation.
Gridded land use data for the conterminous United States 1940–2015
Authors: Mc Shane Caitlín , Uhl Johannes H. , Leyk Stefan 
Published: August 2022

AbstractMultiple aspects of our society are reflected in how we have transformed land through time. However, limited availability of historical-spatial data at fine granularity have hindered our ability to advance our understanding of the ways in which land was developed over the long-term. Using a proprietary, national housing and property database, which is a result of large-scale, industry-fuelled data harmonization efforts, we created publicly available sequences of gridded surfaces that describe built land use progression in the conterminous United States at fine spatial (i.e., 250 m × 250 m) and temporal resolution (i.e., 1 year - 5 years) between the years 1940 and 2015. There are six land use classes represented in the data product: agricultural, commercial, industrial, residential-owned, residential-income, and recreational facilities, as well as complimentary uncertainty layers informing the users about quantifiable components of data uncertainty. The datasets are part of the Historical Settlement Data Compilation for the U.S. (HISDAC-US) and enable the creation of new knowledge of long-term land use dynamics, opening novel avenues of inquiry across multiple fields of study.
High frequency resistive switching behavior of amorphous TiO2 and NiO
Authors: Bulja Senad , Kopf Rose , Tate Al , Cappuzzo Mark , Kozlov Dmitry , Claussen Holger , Wiegner Dirk , Templ Wolfgang , Mirshekar-Syahkal Dariush 
Published: August 2022

AbstractResistive switching (RS) of Transition Metal Oxides (TMOs) has become not only an attractive choice for the development of next generation non-volatile memory, but also as a suitable family of materials capable of supporting high-frequency and high-speed switching needed for the next generation wireless communication technologies, such as 6G. The exact mechanism of RS is not yet clearly understood; however, it is widely accepted to be related to the formation and rupture of sub-stoichiometric conductive filaments (Magnéli phases) of the respective oxides upon activation. Here, we examine the switching behaviour of amorphous TiO2 and NiO both under the DC regime and in the high frequency mode. We show that the DC resistance of amorphous TiO2 is invariant of the length of the active region. In contrast, the resistance of the NiO samples exhibits a strong dependence on the length, and its DC resistance reduces as the length is increased. We further show that the high frequency switching characteristics of TiO2, reflected in insertion losses in the ON state and isolation in the OFF state, are far superior to those of NiO. Fundamental inferences stem from these findings, which not only enrich our understanding of the mechanism of conduction in binary/multinary oxides but are essential for the enablement of widespread use of binary/multinary oxides in emerging non-volatile memory and 6G mm-wave applications. As an example of a possible application supported by TMOs, is a Reflective-Type Variable Attenuator (RTVA), shown here. It is designed to operate at a centre frequency of 15 GHz. The results indicate that it has a dynamic range of no less than 18 dB with a maximum insertion loss of 2.1 dB.
User engagement in relation to effectiveness of a digital lifestyle intervention (the HealthyMoms app) in pregnancy
Authors: Henriksson Pontus , Migueles Jairo H. , Söderström Emmie , Sandborg Johanna , Maddison Ralph , Löf Marie 
Published: August 2022

AbstractAlthough user engagement is generally considered important for the effectiveness of digital behavior change interventions, there is a lack of such data in pregnancy. The aim of this study was therefore to examine the associations of user engagement with the HealthyMoms app with gestational weight gain, diet quality and physical activity in pregnancy. The study involved secondary analyses of participant data from the intervention group (n = 134) in a randomized controlled trial to determine the effectiveness of a 6-month mHealth intervention (the HealthyMoms app) on gestational weight gain, diet quality and physical activity. In adjusted regression models, the total number of registrations from three self-monitoring features (i.e., for weight-, diet- and physical activity) was associated with lower gestational weight gain (β =  − 0.18, P = 0.043) and improved diet quality (β = 0.17, P = 0.019). These findings were mainly attributable to the associations of physical activity registrations with lower gestational weight gain (β =  − 0.20, P = 0.026) and improved diet quality (β = 0.20, P = 0.006). However, the number of app sessions and page views were not associated with any of the outcomes. Our results may motivate efforts to increase user engagement in digital lifestyle interventions in pregnancy. However, additional studies are needed to further elucidate the influence of different types of user engagement in digital pregnancy interventions on their effectiveness.Trial registration: ClinicalTrials.gov (NCT03298555); https://clinicaltrials.gov/ct2/show/NCT03298555 (date of registration: October 2, 2017; date of first enrolled participant: October 24, 2017).
Nonlinear spectral tunability of pulsed fiber laser with semiconductor optical amplifier
Authors: Bednyakova Anastasia , Khudozhitkova Daria , Turitsyn Sergei 
Published: August 2022

AbstractWe examine spectral properties of radiation in the pulsed fiber lasers using the semiconductor optical amplifier (SOA) as the gain medium. The complex light dynamics that result from the interplay between the fiber propagation effects in the cavity, the nonlinear effects in the SOA and spectral filtering, shift the generated radiation from the central wavelength of the filter. The resulting wavelength of the output radiation depends on the SOA pump power and the bandwidth of the intracavity filter. This offers the possibility of a spectral tunability of the generated pulses through nonlinear dynamics rather than the conventional use of a tunable filter.
Prenatal adherence to the Mediterranean diet decreases the risk of having a small-for-gestational-age baby, ECLIPSES study
Authors: Díaz-López Andrés , Díaz-Torres Sandra , Martín-Luján Francisco , Basora Josep , Arija Victoria 
Published: August 2022

AbstractThere is little evidence regarding the role that consuming a Mediterranean diet (MedDiet) during pregnancy plays in foetal growth. We therefore examined the relationship between maternal MedDiet adherence during pregnancy and anthropometric measures and small-for-gestational-age (SGA) at birth in a Spanish population on the north-eastern Mediterranean coast of Spain. Prospective analysis involved 614 mother–newborn pairs from the ECLIPSES study. Diet during pregnancy was assessed using a validated food frequency questionnaire, and a relative MedDiet score (rMedDiet) was calculated. Neonatal information, including weight, length, head circumference and SGA (< 10th percentile) at birth, was recorded. Multivariable logistic regression analyses were performed. The mean rMedDiet score was 9.8 (SD 2.1), ranging from 5 to 16 points. In the sample, 45% of the women had low (≤ 9 points), 32% had medium (10–11 points), and 22% had high (≥ 12 points) adherence to the rMedDiet. There was no association between rMedDiet and birth weight, length, head circumference or anthropometric indices (weight/length ratio and ponderal index). Pregnant women with a high rMedDiet score had a lower risk of delivering a SGA baby for weight (high vs low, OR = 0.36; 95% CI 0.16–0.79) and head circumference (high vs low, OR = 0.39; 95% CI 0.18–0.86), and a nonsignificant decrease in risk of SGA for length (high vs low, OR = 0.57; 95% CI 0.28–1.17). In conclusion, closer adherence to the MedDiet during pregnancy may have beneficial effects on foetal growth.