bluuebunny/crossref_metadata_2025_split huggingface dataset:
ABCA8-mediated efflux of taurocholic acid contributes to gemcitabine insensitivity in human pancreatic cancer via the S1PR2-ERK pathway
Authors: Yang Chunmei , Yuan Hui , Gu Jinyang , Xu Dengfei , Wang Mingwei , Qiao Jie , Yang Xi , Zhang Jian , Yao Ming , Gu Jianren , Tu Hong , Gan Yu 
Published: January 2021

AbstractThe development of resistance to anticancer drugs is believed to cause chemotherapy failure in pancreatic cancer (PC). The efflux of anticancer drugs mediated by ATP-binding cassette (ABC) transporters is a widely accepted mechanism for chemoresistance, but for ABCA subfamily members, which are characterized by their ability to transport lipids and cholesterol, its role in chemoresistance remains unknown. Here we found that the expression of ABCA8, a member of ABCA subfamily transporters, was significantly increased in human PC cells after gemcitabine (GEM) treatment, as well as in established GEM-resistant (Gem-R) PC cells. Importantly, ABCA8 knockdown reversed the chemoresistance phenotype of Gem-R cells, whereas ABCA8 overexpression significantly decreased the sensitivity of human PC cells to GEM, both in vitro and in vivo, demonstrating an important role of ABCA8 in regulating chemosensitivity. Moreover, our results showed that treatment with taurocholic acid (TCA), an endogenous substrate of ABCA8, also induced GEM insensitivity in PC cells. We further demonstrated that ABCA8 mediates the efflux of TCA out of PC cells, and that extracellular TCA activates extracellular signal-regulated kinase (ERK) signaling via the sphingosine 1-phosphate receptor 2 (S1PR2), which is responsible for ABCA8-induced GEM ineffectiveness. Together, these findings reveal a novel TCA-related mechanism of ABCA subfamily transporter-mediated chemoresistance that goes beyond the role of a drug pump and suggest ABCA8 or the TCA-S1RP2-ERK pathway as potential targets for improving the effectiveness of and overcoming the resistance to chemotherapy in PC.
GDF15 promotes glioma stem cell-like phenotype via regulation of ERK1/2–c-Fos–LIF signaling
Authors: Zhu Shan , Yang Ning , Guan Yi , Wang Xue , Zang Guoxia , Lv Xinping , Deng Shuanglin , Wang Wan , Li Tete , Chen Jingtao 
Published: January 2021

AbstractGrowth differentiation factor 15 (GDF15), a member of the transforming growth factor β family, is associated with tumor progression, metastasis, and cell apoptosis. However, controversy persists regarding the role of GDF15 in different tumor types, and its function in glioma stem cells (GSCs) remains unknown. Here, we report that GDF15 promotes the GSC-like phenotype in GSC-like cells (GSCLCs) through the activation of leukemia inhibitor factor (LIF)–STAT3 signaling. Mechanistically, GDF15 was found to upregulate expression of the transcription factor c-Fos, which binds to the LIF promoter, leading to enhanced transcription of LIF in GSCLCs. Furthermore, GDF15 may activate the ERK1/2 signaling pathway in GSCLCs, and the upregulation of LIF expression and the GSC-like phenotype was dependent on ERK1/2 signaling. In addition, the small immunomodulator imiquimod induced GDF15 expression, which in turn activated the LIF–STAT3 pathway and subsequently promoted the GSC-like phenotype in GSCLCs. Thus, our results demonstrate that GDF15 can act as a proliferative and pro-stemness factor for GSCs, and therefore, it may represent a potential therapeutic target in glioma treatment.
Toll-like receptor 7 deficiency suppresses type 1 diabetes development by modulating B-cell differentiation and function
Authors: Huang Juan , Peng Jian , Pearson James Alexander , Efthimiou Georgios , Hu Youjia , Tai Ningwen , Xing Yanpeng , Zhang Luyao , Gu Jianlei , Jiang Jianping , Zhao Hongyu , Zhou Zhiguang , Wong F. Susan , Wen Li 
Published: January 2021

AbstractInnate immunity mediated by Toll-like receptors (TLRs), which can recognize pathogen molecular patterns, plays a critical role in type 1 diabetes development. TLR7 is a pattern recognition receptor that senses single-stranded RNAs from viruses and host tissue cells; however, its role in type 1 diabetes development remains unclear. In our study, we discovered that Tlr7-deficient (Tlr7−/−) nonobese diabetic (NOD) mice, a model of human type 1 diabetes, exhibited a significantly delayed onset and reduced incidence of type 1 diabetes compared with Tlr7-sufficient (Tlr7+/+) NOD mice. Mechanistic investigations showed that Tlr7 deficiency significantly altered B-cell differentiation and immunoglobulin production. Moreover, Tlr7−/− NOD B cells were found to suppress diabetogenic CD4+ T-cell responses and protect immunodeficient NOD mice from developing diabetes induced by diabetogenic T cells. In addition, we found that Tlr7 deficiency suppressed the antigen-presenting functions of B cells and inhibited cytotoxic CD8+ T-cell activation by downregulating the expression of both nonclassical and classical MHC class I (MHC-I) molecules on B cells. Our data suggest that TLR7 contributes to type 1 diabetes development by regulating B-cell functions and subsequent interactions with T cells. Therefore, therapeutically targeting TLR7 may prove beneficial for disease protection.
Double viral vector technology for selective manipulation of neural pathways with higher level of efficiency and safety
Authors: Koshimizu Yoshinori , Isa Kaoru , Kobayashi Kenta , Isa Tadashi 
Published: January 2021

AbstractPathway-selective gene delivery would be critical for future gene therapy against neuropsychiatric disorders, traumatic neuronal injuries, or neurodegenerative diseases, because the impaired functions depend on neural circuits affected by the insults. Pathway-selective gene delivery can be achieved by double viral vector techniques, which combine an injection of a retrograde transport viral vector into the projection area of the target neurons and that of an anterograde viral vector into their somas. In this study, we tested the efficiency of gene delivery with different combinations of viral vectors to the pathway extending from the ventral tegmental area (VTA) to the cortical motor regions in rats, considered to be critical in the promotion of motor recovery from neural injuries. It was found that retrograde recombinant adeno-associated virus 2-retro (rAAV2reto) combined with anterograde AAVDJ (type2/type4/type5/type8/type9/avian/bovine/caprine chimera) exhibited the highest transduction efficiency in the short term (3–6 weeks) but high toxicity in the long term (3 months). In contrast, the same rAAV2reto combined with anterograde AAV5 displayed moderate transduction efficiency in the short term but low toxicity in the long term. These data suggest that the combination of anterograde AAV5 and retrograde rAAV2retro is suitable for safe and efficient gene delivery to the VTA-cortical pathway.
Validation of an IFN-gamma ELISpot assay to measure cellular immune responses against viral antigens in non-human primates
Authors: Yang Fan , Patton Kathryn , Kasprzyk Theresa , Long Brian , Gupta Soumi , Zoog Stephen J. , Tracy Kristin , Vettermann Christian 
Published: January 2021

AbstractAdeno-Associated Virus (AAV)-based gene therapy vectors are in development for many inherited human disorders. In nonclinical studies, cellular immune responses mediated by cytotoxic T cells may target vector-transduced cells, which could impact safety and efficacy. Here, we describe the bioanalytical validation of an interferon-gamma (IFN-γ)-based Enzyme-Linked Immunospot (ELISpot) assay for measuring T cell responses against viral antigens in cynomolgus monkeys. Since ELISpots performed with antigen-derived peptides offer a universal assay format, method performance characteristics were validated using widely available peripheral blood mononuclear cells (PBMCs) responsive to cytomegalovirus peptides. The limit of detection and confirmatory cut point were established using statistical methods; precision, specificity, and linearity were confirmed. Monkey PBMCs from an AAV5 gene therapy study were then analyzed, using peptide pools spanning the vector capsid and transgene product. AAV5-specific T cell responses were detected only in 2 of 18 monkeys at Day 28, but not at Day 13 and 56 after vector administration, with no correlation to liver enzyme elevations or transgene expression levels. No transgene product-specific T cell responses occurred. In conclusion, while viral peptide-specific IFN-γ ELISpots can be successfully validated for monkey PBMCs, monitoring peripheral T cell responses in non-clinical AAV5 gene therapy studies was of limited value to interpret safety or efficacy.
Multi-atom quasiparticle scattering interference for superconductor energy-gap symmetry determination
Authors: Sharma Rahul , Kreisel Andreas , Sulangi Miguel Antonio , Böker Jakob , Kostin Andrey , Allan Milan P. , Eisaki H. , Böhmer Anna E. , Canfield Paul C. , Eremin Ilya , Séamus Davis J. C. , Hirschfeld P. J. , Sprau Peter O. 
Published: January 2021

AbstractComplete theoretical understanding of the most complex superconductors requires a detailed knowledge of the symmetry of the superconducting energy-gap $${\mathrm{{\Delta}}}_{\mathbf{k}}^\alpha$$

Δ

k

α

, for all momenta k on the Fermi surface of every band α. While there are a variety of techniques for determining $$|{\mathrm{{\Delta}}}_{\mathbf{k}}^\alpha |$$

∣

Δ

k

α

∣

, no general method existed to measure the signed values of $${\mathrm{{\Delta}}}_{\mathbf{k}}^\alpha$$

Δ

k

α

. Recently, however, a technique based on phase-resolved visualization of superconducting quasiparticle interference (QPI) patterns, centered on a single non-magnetic impurity atom, was introduced. In principle, energy-resolved and phase-resolved Fourier analysis of these images identifies wavevectors connecting all k-space regions where $${\mathrm{{\Delta}}}_{\mathbf{k}}^\alpha$$

Δ

k

α

has the same or opposite sign. But use of a single isolated impurity atom, from whose precise location the spatial phase of the scattering interference pattern must be measured, is technically difficult. Here we introduce a generalization of this approach for use with multiple impurity atoms, and demonstrate its validity by comparing the $${\mathrm{{\Delta}}}_{\mathbf{k}}^\alpha$$

Δ

k

α

it generates to the $${\mathrm{{\Delta}}}_{\mathbf{k}}^\alpha$$

Δ

k

α

determined from single-atom scattering in FeSe where s± energy-gap symmetry is established. Finally, to exemplify utility, we use the multi-atom technique on LiFeAs and find scattering interference between the hole-like and electron-like pockets as predicted for $${\mathrm{{\Delta}}}_{\mathbf{k}}^\alpha$$

Δ

k

α

of opposite sign.
The traded water footprint of global energy from 2010 to 2018
Authors: Chini Christopher M. , Peer Rebecca A. M. 
Published: January 2021

AbstractThe energy-water nexus describes the requirement of water-for-energy and energy-for-water. The consumption of water in the production and generation of energy resources is also deemed virtual water. Pairing the virtual water estimates for energy with international trade data creates a virtual water trade network, facilitating analysis of global water resources management. In this database, we identify the virtual water footprints for the trade of eleven different energy commodities including fossil fuels, biomass, and electricity. Additionally, we provide the necessary scripts for downloading and pairing trade data with the virtual water footprints to create a virtual water trade network. The resulting database contains country-to-country virtual water trade from 2010–2018, broken down by commodity. The purpose of this data descriptor is to provide detailed methods and validation of the dataset beyond the complementary research publication. The resulting database provides opportunities to understand global energy-related water demands and advance future global water resources research.
Opioid use may be associated with postoperative complications in myotonic dystrophy type 1 with high-grade muscular impairment
Authors: Kim Chan-Sik , Park Jin-Mo , Park Donghwi , Kim Doo-Hwan , Park Jin-Sung 
Published: January 2021

AbstractIndividuals with myotonic dystrophy type 1 (DM1) reportedly have a higher risk of postoperative complications than those without DM1; however, factors related to perioperative complications in DM1 patients remain unclear. We aimed to identify the risk factors that may be associated with postoperative complications in DM1 patients. We reviewed medical records of 256 patients with DM1 from 1998 to 2018, among whom 42 (16.4%) had previously undergone 51 surgeries under general and regional anaesthesia. Among the 42 patients, 11 (21.5%) had 13 postoperative complications including respiratory complications, sustained hypotension, wound infection and dehiscence, artery thrombosis and occlusion, and delayed recovery from anaesthesia. There were significant inter-group differences between the non-complicated and complicated groups considering the following parameters: high-grade (≥ 3) muscular impairment rating scale (MIRS), extubation time, postoperative opioid use, and hospital length of stay. Furthermore, univariate analysis revealed that an MIRS score ≥ 3 (odds ratio [OR] 9.346, confidence interval [CI] 1.761–49.595, p = 0.009) and postoperative opioid use (OR 8.000, CI 1.772–36.127, p = 0.007) were the only statistically significant factors. Therefore, clinicians should be cautious in administering opioids, particularly in patients with a high-grade MIRS score during the perioperative period.
Mortality in neonates with giant omphalocele subjected to a surgical technique in Barranquilla, Colombia from 1994 to 2019
Authors: Barrios-Sanjuanelo Alexander , Abelló-Munarriz Cristóbal , Cardona-Arias Jaiberth Antonio 
Published: January 2021

AbstractNo studies of the efficacy and safety of surgical techniques for the primary closure of giant omphalocele have been performed in Colombia. To determine the mortality rate and factors associated with mortality in neonates with giant omphalocele subjected to the surgical technique of early closure with a surgical silo described by Abello in Barranquilla, Colombia from 1994 to 2019. Retrospective cohort study of 30 neonates diagnosed with giant omphalocele and subjected to early closure of the defect. Medical history data were collected, information bias was controlled for, and descriptive statistical analysis was performed using Fisher’s exact test and the Mann–Whitney U test in SPSS 25.0. Of the patients in the cohort, 36.7% presented technique-related complications, 56.7% developed sepsis, 23.3% had low birth weight, 26.7% were preterm births, 43.3% had other malformations, 26.7% had congenital heart defects, and 13.3% presented pulmonary hypertension. The mean hospital stay was 26 days. The mortality rate was 16.7%; it was significantly higher among patients with other malformations, congenital heart defects, pentalogy of Cantrell and pulmonary hypertension. The Abello technique for the treatment of giant omphalocele showed a high neonatal survival rate and a low rate of procedure-related complications. The main factors associated with the death of neonatal patients were the presence of other malformations, congenital heart defect, pentalogy of Cantrell and pulmonary hypertension.
Facial recognition technology can expose political orientation from naturalistic facial images
Authors: Kosinski Michal 
Published: January 2021

AbstractUbiquitous facial recognition technology can expose individuals’ political orientation, as faces of liberals and conservatives consistently differ. A facial recognition algorithm was applied to naturalistic images of 1,085,795 individuals to predict their political orientation by comparing their similarity to faces of liberal and conservative others. Political orientation was correctly classified in 72% of liberal–conservative face pairs, remarkably better than chance (50%), human accuracy (55%), or one afforded by a 100-item personality questionnaire (66%). Accuracy was similar across countries (the U.S., Canada, and the UK), environments (Facebook and dating websites), and when comparing faces across samples. Accuracy remained high (69%) even when controlling for age, gender, and ethnicity. Given the widespread use of facial recognition, our findings have critical implications for the protection of privacy and civil liberties.
Changing patterns in aerosol vertical distribution over South and East Asia
Authors: Ratnam M. Venkat , Prasad P. , Raj S. T. Akhil , Raman M. Roja , Basha Ghouse 
Published: January 2021

AbstractChanging patterns in aerosol concentrations over the Asian region is well documented with a concurrent increase over India and a marked reduction over China. However, aerosol vertical distribution in the changing climate is not fully understood. By combining long-term satellite observations from MODIS and CALIOP, here we show rapid changes in the aerosol vertical distribution over the South and East Asia covering India and China. A statistically significant decreasing (increasing) trend in the boundary layer (free troposphere) aerosol concentrations is noticed over India. ERA-Interim reanalysis model suggests that this increase in free tropospheric aerosol concentrations are due to the lifting of boundary layer pollutants through an increase in convection (and vertical velocity) in a changing climate. In contrast, a consistent decreasing trend is observed over China irrespective of the altitude. Interestingly, a decreasing trend in Aerosol Optical Depth is observed over the northwest India and we relate this to an observed increase in precipitation leading to increase in the vegetation. It is also found that long-term oscillations like QBO, ENSO and solar cycle significantly affect the aerosol concentrations. Thus, it is prudent to conclude that background meteorology and dynamics play an important role in changing patterns of aerosol vertical distribution.
Continuity of the Middle Stone Age into the Holocene
Authors: Scerri Eleanor M. L. , Niang Khady , Candy Ian , Blinkhorn James , Mills William , Cerasoni Jacopo N. , Bateman Mark D. , Crowther Alison , Groucutt Huw S. 
Published: January 2021

AbstractThe African Middle Stone Age (MSA, typically considered to span ca. 300–30 thousand years ago [ka]), represents our species’ first and longest lasting cultural phase. Although the MSA to Later Stone Age (LSA) transition is known to have had a degree of spatial and temporal variability, recent studies have implied that in some regions, the MSA persisted well beyond 30 ka. Here we report two new sites in Senegal that date the end of the MSA to around 11 ka, the youngest yet documented MSA in Africa. This shows that this cultural phase persisted into the Holocene. These results highlight significant spatial and temporal cultural variability in the African Late Pleistocene, consistent with genomic and palaeoanthropological hypotheses that significant, long-standing inter-group cultural differences shaped the later stages of human evolution in Africa.
Association between long-range temporal correlations in intrinsic EEG activity and subjective sense of identity
Authors: Sugimura Kazumi , Iwasa Yasuhiro , Kobayashi Ryota , Honda Tatsuru , Hashimoto Junya , Kashihara Shiho , Zhu Jianhong , Yamamoto Kazuki , Kawahara Tsuyoshi , Anno Mayo , Nakagawa Risa , Hatano Kai , Nakao Takashi 
Published: January 2021

AbstractThe long-range temporal correlation (LRTC) in resting-state intrinsic brain activity is known to be associated with temporal behavioral patterns, including decision making based on internal criteria such as self-knowledge. However, the association between the neuronal LRTC and the subjective sense of identity remains to be explored; in other words, whether our subjective sense of consistent self across time relates to the temporal consistency of neural activity. The present study examined the relationship between the LRTC of resting-state scalp electroencephalography (EEG) and a subjective sense of identity measured by the Erikson Psychosocial Stage Inventory (EPSI). Consistent with our prediction based on previous studies of neuronal-behavioral relationships, the frontocentral alpha LRTC correlated negatively with identity confusion. Moreover, from the descriptive analyses, centroparietal beta LRTC showed negative correlations with identity confusion, and frontal theta LRTC showed positive relationships with identity synthesis. These results suggest that more temporal consistency (reversely, less random noise) in intrinsic brain activity is associated with less confused and better-synthesized identity. Our data provide further evidence that the LRTC of intrinsic brain activity might serve as a noise suppression mechanism at the psychological level.
Crystal structure of a thermophilic fungal cyanase and its implications on the catalytic mechanism for bioremediation
Authors: Ranjan Bibhuti , Choi Philip H. , Pillai Santhosh , Permaul Kugenthiren , Tong Liang , Singh Suren 
Published: January 2021

AbstractCyanase catalyzes the bicarbonate-dependent degradation of cyanate to produce ammonia and carbon dioxide, and ammonia is a considerable alternative nitrogen source. Strikingly, the cyanase from the thermophilic fungus Thermomyces lanuginosus (Tl-Cyn) has the highest catalytic efficiency reported among these enzymes. However, its molecular mechanism of action is not clearly understood, because currently there is no structural information available on fungal cyanases. Here we report the crystal structure of Tl-Cyn in complex with inhibitors malonate and formate at 2.2 Å resolution. The structure reveals extensive interactions at the subunit interfaces in a dimer, and a decamer is formed by a pentamer of these dimers. Our biochemical, kinetic and mutagenesis studies confirm the structural observations on the complex and provide further insights into its catalytic mechanism and inhibition. The structure has also aided the creation of a mutant enzyme with enhanced catalytic activity, and such enzymes may have the potential for biotechnological applications, including biotransformation and bioremediation. Moreover, other fungal cyanases with potentially high catalytic activity could also be predicted based on the Tl-Cyn structure, as the active site region among fungal cyanases are highly conserved.
Mechanism understanding in cryo atomic layer etching of SiO2 based upon C4F8 physisorption
Authors: Antoun G. , Tillocher T. , Lefaucheux P. , Faguet J. , Maekawa K. , Dussart R. 
Published: January 2021

AbstractCryogenic Atomic Layer Etching (cryo-ALE) of SiO2based on alternating a C4F8molecule physisorption step and an argon plasma step, has been enhanced thanks to a better understanding of the mechanism. First, we used Quadrupole Mass spectrometry (QMS) and spectroscopic ellipsometry analyses to evaluate the residence time of physisorbed C4F8molecules versus temperature and pressure on SiO2surface. QMS monitoring of the SiF4etching by-product also enabled to follow the self-limiting etching behavior. Finally, a SiO2cryo-ALE process was proposed at a temperature of − 90 °C resulting in a very linear etch over 150 cycles and an Etch amount Per Cycle as low as 0.13 nm/cycle.