bluuebunny/crossref_metadata_2025_split huggingface dataset:
The methyltransferase METTL3 negatively regulates nonalcoholic steatohepatitis (NASH) progression
Authors: Li Xinzhi , Yuan Bingchuan , Lu Min , Wang Yuqin , Ding Na , Liu Chunhong , Gao Ming , Yao Zhicheng , Zhang Shiyan , Zhao Yujun , Xie Liwei , Chen Zheng 
Published: December 2021

AbstractNonalcoholic steatohepatitis (NASH) is a key step in the progression of nonalcoholic fatty liver (NAFL) to cirrhosis. However, the molecular mechanisms of the NAFL-to-NASH transition are largely unknown. Here, we identify methyltransferase like 3 (METTL3) as a key negative regulator of NASH pathogenesis. Hepatocyte-specific deletion of Mettl3 drives NAFL-to-NASH progression by increasing CD36-mediated hepatic free fatty acid uptake and CCL2-induced inflammation, which is due to increased chromatin accessibility in the promoter region of Cd36 and Ccl2. Antibody blockade of CD36 and CCL2 ameliorates NASH progression in hepatic Mettl3 knockout mice. Hepatic overexpression of Mettl3 protects against NASH progression by inhibiting the expression of CD36 and CCL2. Mechanistically, METTL3 directly binds to the promoters of the Cd36 and Ccl2 genes and recruits HDAC1/2 to induce deacetylation of H3K9 and H3K27 in their promoters, thus suppressing Cd36 and Ccl2 transcription. Furthermore, METTL3 is translocated from the nucleus to the cytosol in NASH, which is associated with CDK9-mediated phosphorylation of METTL3. Our data reveal a mechanism by which METTL3 negatively regulates hepatic Cd36 and Ccl2 gene transcription via a histone modification pathway for protection against NASH progression.
Robustly printable freeform thermal metamaterials
Authors: Sha Wei , Xiao Mi , Zhang Jinhao , Ren Xuecheng , Zhu Zhan , Zhang Yan , Xu Guoqiang , Li Huagen , Liu Xiliang , Chen Xia , Gao Liang , Qiu Cheng-Wei , Hu Run 
Published: December 2021

AbstractThermal metamaterials have exhibited great potential on manipulating, controlling and processing the flow of heat, and enabled many promising thermal metadevices, including thermal concentrator, rotator, cloak, etc. However, three long-standing challenges remain formidable, i.e., transformation optics-induced anisotropic material parameters, the limited shape adaptability of experimental thermal metadevices, and a priori knowledge of background temperatures and thermal functionalities. Here, we present robustly printable freeform thermal metamaterials to address these long-standing difficulties. This recipe, taking the local thermal conductivity tensors as the input, resorts to topology optimization for the freeform designs of topological functional cells (TFCs), and then directly assembles and prints them. Three freeform thermal metadevices (concentrator, rotator, and cloak) are specifically designed and 3D-printed, and their omnidirectional concentrating, rotating, and cloaking functionalities are demonstrated both numerically and experimentally. Our study paves a powerful and flexible design paradigm toward advanced thermal metamaterials with complex shapes, omnidirectional functionality, background temperature independence, and fast-prototyping capability.
Proteomic profiling of MIS-C patients indicates heterogeneity relating to interferon gamma dysregulation and vascular endothelial dysfunction
Authors: Diorio Caroline , Shraim Rawan , Vella Laura A. , Giles Josephine R. , Baxter Amy E. , Oldridge Derek A. , Canna Scott W. , Henrickson Sarah E. , McNerney Kevin O. , Balamuth Frances , Burudpakdee Chakkapong , Lee Jessica , Leng Tomas , Farrel Alvin , Lambert Michele P. , Sullivan Kathleen E. , Wherry E. John , Teachey David T. , Bassiri Hamid , Behrens Edward M. 
Published: December 2021

AbstractMulti-system Inflammatory Syndrome in Children (MIS-C) is a major complication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in pediatric patients. Weeks after an often mild or asymptomatic initial infection with SARS-CoV-2 children may present with a severe shock-like picture and marked inflammation. Children with MIS-C present with varying degrees of cardiovascular and hyperinflammatory symptoms. Here we perform a comprehensive analysis of the plasma proteome of more than 1400 proteins in children with SARS-CoV-2. We hypothesize that the proteome would reflect heterogeneity in hyperinflammation and vascular injury, and further identify pathogenic mediators of disease. We show that protein signatures demonstrate overlap between MIS-C, and the inflammatory syndromes macrophage activation syndrome (MAS) and thrombotic microangiopathy (TMA). We demonstrate that PLA2G2A is an important marker of MIS-C that associates with TMA. We find that IFNγ responses are dysregulated in MIS-C patients, and that IFNγ levels delineate clinical heterogeneity.
Forward and reverse genetic dissection of morphogenesis identifies filament-competent Candida auris strains
Authors: Santana Darian J. , O’Meara Teresa R. 
Published: December 2021

AbstractCandida auris is an emerging healthcare-associated pathogen of global concern. Recent reports have identified C. auris isolates that grow in cellular aggregates or filaments, often without a clear genetic explanation. To investigate the regulation of C. auris morphogenesis, we applied an Agrobacterium-mediated transformation system to all four C. auris clades. We identified aggregating mutants associated with disruption of chitin regulation, while disruption of ELM1 produced a polarized, filamentous growth morphology. We developed a transiently expressed Cas9 and sgRNA system for C. auris that significantly increased targeted transformation efficiency across the four C. auris clades. Using this system, we confirmed the roles of C. auris morphogenesis regulators. Morphogenic mutants showed dysregulated chitinase expression, attenuated virulence, and altered antifungal susceptibility. Our findings provide insights into the genetic regulation of aggregating and filamentous morphogenesis in C. auris. Furthermore, the genetic tools described here will allow for efficient manipulation of the C. auris genome.
Ultra-high thermal stability of sputtering reconstructed Cu-based catalysts
Authors: Yu Jiafeng , Sun Xingtao , Tong Xin , Zhang Jixin , Li Jie , Li Shiyan , Liu Yuefeng , Tsubaki Noritatsu , Abe Takayuki , Sun Jian 
Published: December 2021

AbstractThe rational design of high-temperature endurable Cu-based catalysts is a long-sought goal since they are suffering from significant sintering. Establishing a barrier on the metal surface by the classical strong metal-support interaction (SMSI) is supposed to be an efficient way for immobilizing nanoparticles. However, Cu particles were regarded as impossible to form classical SMSI before irreversible sintering. Herein, we fabricate the SMSI between sputtering reconstructed Cu and flame-made LaTiO2 support at a mild reduction temperature, exhibiting an ultra-stable performance for more than 500 h at 600 °C. The sintering of Cu nanoparticles is effectively suppressed even at as high as 800 °C. The critical factors to success are reconstructing the electronic structure of Cu atoms in parallel with enhancing the support reducibility, which makes them adjustable by sputtering power or decorated supports. This strategy will extremely broaden the applications of Cu-based catalysts at more severe conditions and shed light on establishing SMSI on other metals.
Type-I collagen produced by distinct fibroblast lineages reveals specific function during embryogenesis and Osteogenesis Imperfecta
Authors: Chen Yang , Yang Sujuan , Lovisa Sara , Ambrose Catherine G. , McAndrews Kathleen M. , Sugimoto Hikaru , Kalluri Raghu 
Published: December 2021

AbstractType I collagen (Col1) is the most abundant protein in mammals. Col1 contributes to 90% of the total organic component of bone matrix. However, the precise cellular origin and functional contribution of Col1 in embryogenesis and bone formation remain unknown. Single-cell RNA-sequencing analysis identifies Fap+ cells and Fsp1+ cells as the major contributors of Col1 in the bone. We generate transgenic mouse models to genetically delete Col1 in various cell lineages. Complete, whole-body Col1 deletion leads to failed gastrulation and early embryonic lethality. Specific Col1 deletion in Fap+ cells causes severe skeletal defects, with hemorrhage, edema, and prenatal lethality. Specific Col1 deletion in Fsp1+ cells results in Osteogenesis Imperfecta-like phenotypes in adult mice, with spontaneous fractures and compromised bone healing. This study demonstrates specific contributions of mesenchymal cell lineages to Col1 production in organogenesis, skeletal development, and bone formation/repair, with potential insights into cell-based therapy for patients with Osteogenesis Imperfecta.
Stable isotopes in global lakes integrate catchment and climatic controls on evaporation
Authors: Vystavna Yuliya , Harjung Astrid , Monteiro Lucilena R. , Matiatos Ioannis , Wassenaar Leonard I. 
Published: December 2021

AbstractGlobal warming is considered a major threat to Earth’s lakes water budgets and quality. However, flow regulation, over-exploitation, lack of hydrological data, and disparate evaluation methods hamper comparative global estimates of lake vulnerability to evaporation. We have analyzed the stable isotope composition of 1257 global lakes and we find that most lakes depend on precipitation and groundwater recharge subsequently altered by catchment and lake evaporation processes. Isotope mass-balance modeling shows that ca. 20% of water inflow in global lakes is lost through evaporation and ca. 10% of lakes in arid and temperate zones experience extreme evaporative losses >40 % of the total inflow. Precipitation amount, limnicity, wind speed, relative humidity, and solar radiation are predominant controls on lake isotope composition and evaporation, regardless of the climatic zone. The promotion of systematic global isotopic monitoring of Earth’s lakes provides a direct and comparative approach to detect the impacts of climatic and catchment-scale changes on water-balance and evaporation trends.
Single molecule kinetics of bacteriorhodopsin by HS-AFM
Authors: Perrino Alma P. , Miyagi Atsushi , Scheuring Simon 
Published: December 2021

AbstractBacteriorhodopsin is a seven-helix light-driven proton-pump that was structurally and functionally extensively studied. Despite a wealth of data, the single molecule kinetics of the reaction cycle remain unknown. Here, we use high-speed atomic force microscopy methods to characterize the single molecule kinetics of wild-type bR exposed to continuous light and short pulses. Monitoring bR conformational changes with millisecond temporal resolution, we determine that the cytoplasmic gate opens 2.9 ms after photon absorption, and stays open for proton capture for 13.2 ms. Surprisingly, a previously active protomer cannot be reactivated for another 37.6 ms, even under excess continuous light, giving a single molecule reaction cycle of ~20 s−1. The reaction cycle slows at low light where the closed state is prolonged, and at basic or acidic pH where the open state is extended.
Cellular inertia
Authors: Ishiwata Ryosuke , Iwasa Masatomo 
Published: December 2021

AbstractIt has been experimentally reported that chemotactic cells exhibit cellular memory, that is, a tendency to maintain the migration direction despite changes in the chemoattractant gradient. In this study, we analyzed a phenomenological model assuming the presence of cellular inertia, as well as a response time in motility, resulting in the reproduction of the cellular memory observed in the previous experiments. According to the analysis, the cellular motion is described by the superposition of multiple oscillative functions induced by the multiplication of the oscillative polarity and motility. The cellular intertia generates cellular memory by regulating phase differences between those oscillative functions. By applying the theory to the experimental data, the cellular inertia was estimated at $$m=3-6$$

m
=
3
-
6

min. In addition, physiological parameters, such as response time in motility and intracellular processing speed, were also evaluated. The agreement between the experiemental data and theory suggests the possibility of the presence of the response time in motility, which has never been biologically verified and should be explored in the future.
Using imputation to provide harmonized longitudinal measures of cognition across AIBL and ADNI
Authors: Shishegar Rosita , Cox Timothy , Rolls David , Bourgeat Pierrick , Doré Vincent , Lamb Fiona , Robertson Joanne , Laws Simon M. , Porter Tenielle , Fripp Jurgen , Tosun Duygu , Maruff Paul , Savage Greg , Rowe Christopher C. , Masters Colin L. , Weiner Michael W. , Villemagne Victor L. , Burnham Samantha C. 
Published: December 2021

AbstractTo improve understanding of Alzheimer’s disease, large observational studies are needed to increase power for more nuanced analyses. Combining data across existing observational studies represents one solution. However, the disparity of such datasets makes this a non-trivial task. Here, a machine learning approach was applied to impute longitudinal neuropsychological test scores across two observational studies, namely the Australian Imaging, Biomarkers and Lifestyle Study (AIBL) and the Alzheimer's Disease Neuroimaging Initiative (ADNI) providing an overall harmonised dataset. MissForest, a machine learning algorithm, capitalises on the underlying structure and relationships of data to impute test scores not measured in one study aligning it to the other study. Results demonstrated that simulated missing values from one dataset could be accurately imputed, and that imputation of actual missing data in one dataset showed comparable discrimination (p < 0.001) for clinical classification to measured data in the other dataset. Further, the increased power of the overall harmonised dataset was demonstrated by observing a significant association between CVLT-II test scores (imputed for ADNI) with PET Amyloid-β in MCI APOE-ε4 homozygotes in the imputed data (N = 65) but not for the original AIBL dataset (N = 11). These results suggest that MissForest can provide a practical solution for data harmonization using imputation across studies to improve power for more nuanced analyses.
Pyrithione metal (Cu, Ni, Ru) complexes as photo-catalysts for styrene oxide production
Authors: Dasireddy Venkata D. B. C. , Kladnik Jerneja , Korošec Romana Cerc , Likozar Blaž , Turel Iztok 
Published: December 2021

AbstractSelective photochemical oxidation of styrene was performed in an active acetonitrile medium, using H2O2 with or without ultraviolet (UV) light radiation. Pyrithione metal complexes (M–Pth: M = Cu(II), Ni(II), Ru(II); Pth = 2-mercaptopyridine-N-oxide) were used as catalysts. Catalytic testing measurements were done by varying the time, chemical reaction temperature and H2O2 concentration with or without UV energy. Epoxide styrene oxide (SO), benzaldehyde and acetophenone were the major synthesized products. A high batch rate, conversion and selectivity towards SO was shown in the presence of UV. A minor constant formation of CO2 was observed in the stream. Coordinated Ru-based compounds demonstrated the highest process productivity of SO at 60 °C. The effect of the functional alkyl substituent on the ligand Pth, attached to the specific ruthenium(II) centre, decreased the activity of the substance. Ni-Pth selectively yielded benzaldehyde. The stability of the catalysts was examined by applying nuclear magnetic resonance (NMR) spectroscopy and thermogravimetric analysis coupled with mass spectrometry. Tested metal complexes with pyrithione (M–Pth) exhibited excellent reuse recyclability up to 3 cycles.
Forecasting of excavation problems for high-rise building in Vietnam using planet optimization algorithm
Authors: Sang-To Thanh , Hoang-Le Minh , Khatir Samir , Mirjalili Seyedali , Wahab Magd Abdel , Cuong-Le Thanh 
Published: December 2021

AbstractIn this paper, a new method in forecasting the horizontal displacement of diaphragm wall (D.W.) for high-rise buildings is introduced. A new stochastic optimizer, called Planet Optimization Algorithm (P.O.A.), is employed to assess how proper finite element (F.E.) simulation is against field data. The process is adopted for a real phased excavation measured at the field. To automatically run the iterative optimization tasks, a source code is constructed directly in the Geotechnical Engineering Software (PLAXIS) by using Python to ensure that the operation between optimization algorithm and F.E. simulations are smooth to guarantee the accuracy of the complex calculation for the soil problem. The proposed process consists of two steps. (1) The parameters will be optimized at the early phases of the excavation. (2) The responses of D.W. displacements are forecasted at the subsequent phases. The aim of the process is to predict the displacements of D.W. of the building from the result of the nearby excavation or to provide early warning about the risks of excavation that may happen under vital phases. The proposed procedure also provides an effective method for optimization-based soil parameters updating in real engineering practice.
CXCR4 blockade reduces the severity of murine heart allograft rejection by plasmacytoid dendritic cell-mediated immune regulation
Authors: Fu Jian , Lehmann Christian H. K. , Wang Xinning , Wahlbuhl Mandy , Allabauer Ida , Wilde Benjamin , Amon Lukas , Dolff Sebastian , Cesnjevar Robert , Kribben Andreas , Woelfle Joachim , Rascher Wolfgang , Hoyer Peter F. , Dudziak Diana , Witzke Oliver , Hoerning André 
Published: December 2021

AbstractAllograft-specific regulatory T cells (Treg cells) are crucial for long-term graft acceptance after transplantation. Although adoptive Treg cell transfer has been proposed, major challenges include graft-specificity and stability. Thus, there is an unmet need for the direct induction of graft-specific Treg cells. We hypothesized a synergism of the immunotolerogenic effects of rapamycin (mTOR inhibition) and plerixafor (CXCR4 antagonist) for Treg cell induction. Thus, we performed fully-mismatched heart transplantations and found combination treatment to result in prolonged allograft survival. Moreover, fibrosis and myocyte lesions were reduced. Although less CD3+ T cell infiltrated, higher Treg cell numbers were observed. Noteworthy, this was accompanied by a plerixafor-dependent plasmacytoid dendritic cells-(pDCs)-mobilization. Furthermore, in vivo pDC-depletion abrogated the plerixafor-mediated Treg cell number increase and reduced allograft survival. Our pharmacological approach allowed to increase Treg cell numbers due to pDC-mediated immune regulation. Therefore pDCs can be an attractive immunotherapeutic target in addition to plerixafor treatment.
Light makeup decreases receivers’ negative emotional experience
Authors: Zhang Ling , Chen Wenfeng , Liu Menghan , Ou Yuxiao , Xu Erjia , Hu Ping 
Published: December 2021

AbstractMakeup is widely used in modern society and has a positive effect on perceived attractiveness. However, little is known about the other possible outcomes of makeup use. In this study, we investigated whether makeup enhances a receiver’s emotional experience. Dynamic faces with or without makeup are presented in Experiments 1 and 2. Participants were asked to imagine themselves video chatting with a target person (expresser) with different expressions: neutral, angry, sad, or happy, and then to appraise their own subjective emotional experience. Emotional valence, arousal, and willingness to communicate were also assessed in Experiment 2. The results showed that makeup improved perceived facial attractiveness and increased the willingness to communicate. More importantly, it revealed that wearing makeup could weaken receivers’ negative experiences arising from the angry and sad conditions, which is not the case for the non-makeup condition, but could not affect the happy contagion. Furthermore, incremental changes in the amount of makeup were not accompanied by incremental changes in emotional appraisal (valence and arousal). Overall, we found that makeup may affect emotional contagion and interpersonal communication. Whether the alleviated negative experience due to makeup is adaptive may need further discussion.
Diplazium esculentum (Retz.) Sw. reduces BACE-1 activities and amyloid peptides accumulation in Drosophila models of Alzheimer’s disease
Authors: Kunkeaw Thanit , Suttisansanee Uthaiwan , Trachootham Dunyaporn , Karinchai Jirarat , Chantong Boonrat , Potikanond Saranyapin , Inthachat Woorawee , Pitchakarn Pornsiri , Temviriyanukul Piya 
Published: December 2021

AbstractAlzheimer’s disease (AD), one type of dementia, is a complex disease affecting people globally with limited drug treatment. Thus, natural products are currently of interest as promising candidates because of their cost-effectiveness and multi-target abilities. Diplazium esculentum (Retz.) Sw., an edible fern, inhibited acetylcholinesterase in vitro, inferring that it might be a promising candidate for AD treatment by supporting cholinergic neurons. However, evidence demonstrating anti-AD properties of this edible plant via inhibiting of neurotoxic peptides production, amyloid beta (Aβ), both in vitro and in vivo is lacking. Thus, the anti-AD properties of D. esculentum extract both in vitro and in Drosophila models of Aβ-mediated toxicity were elucidated. Findings showed that an ethanolic extract exhibited high phenolics and flavonoids, contributing to antioxidant and inhibitory activities against AD-related enzymes. Notably, the extract acted as a BACE-1 blocker and reduced amyloid beta 42 (Aβ42) peptides in Drosophila models, resulting in improved locomotor behaviors. Information gained from this study suggested that D. esculentum showed potential for AD amelioration and prevention. Further investigations in vertebrates or humans are required to determine the effective doses of D. esculentum against AD, particularly via amyloidogenic pathway.
Amphiregulin can predict treatment resistance to palliative first-line cetuximab plus FOLFIRI chemotherapy in patients with RAS wild-type metastatic colorectal cancer
Authors: Kim Sang-A , Park Hyejoo , Kim Kui-Jin , Kim Ji-Won , Sung Ji Hea , Nam Milang , Lee Ju Hyun , Jung Eun Hee , Suh Koung Jin , Lee Ji Yun , Kim Se Hyun , Lee Jeong-Ok , Kim Jin Won , Kim Yu Jung , Kim Jee Hyun , Bang Soo-Mee , Lee Jong Seok , Lee Keun-Wook 
Published: December 2021

AbstractAmphiregulin (AREG) is an epidermal growth factor receptor (EGFR) ligand. The aim of this study was to investigate the effects of baseline plasma AREG levels in KRAS, NRAS, and BRAF wild-type metastatic colorectal cancer (CRC) on treatment outcome with palliative first-line cetuximab + FOLFIRI chemotherapy. Chemotherapy outcomes were analyzed based on baseline plasma AREG levels. The clinical findings were further validated using an in vitro model of CRC. Among 35 patients, the progression-free survival (PFS) was significantly inferior in patients with high AREG than in those with low AREG levels: 10.9 vs. 24.2 months, respectively (p = 0.008). However, after failure of first-line chemotherapy, AREG levels were associated with neither PFS (4.8 vs. 11.6 months; p = 0.215) nor overall survival (8.4 vs. 13.3 months; p = 0.975). In SNU-C4 and Caco-2 cells which were relatively sensitive to cetuximab among the seven CRC cell lines tested, AREG significantly decreased the anti-proliferative effect of cetuximab (p < 0.05) via AKT and ERK activation. However, after acquiring cetuximab resistance with gradual exposure for more than 6 months, AREG neither increased colony formation nor activated AKT and ERK after cetuximab treatment. Our results suggest that plasma AREG is a potential biomarker to predict clinical outcomes after cetuximab-based chemotherapy.