bluuebunny/crossref_metadata_2025_split huggingface dataset:
Semi‐Brittle Deformation of Talc at the Base of the Seismogenic Zone
Authors: Horn C. M. , Skemer P. 
Published: April 2023

AbstractTalc is commonly found in the cores of exhumed faults and may be important to the dynamics of slip in active fault zones. To understand the rheology of talc at conditions relevant to subduction zones, we conducted torsional deformation experiments at high pressure (1 GPa) and temperatures (450–500°C). Scanning Transmission Electron Microscope imaging revealed a marked decrease in grain size with increasing strain, in addition to the development of grain kinking and nanoporosity. The similarity of these microstructures to talc deformed in natural faults and low‐pressure experiments indicates that the dominant deformation mechanisms of talc are similar across a wide range of depths. We conclude that frictional processes remain an important control on talc rheology even under high normal stresses. However, deformation‐induced porosity could enhance the percolation of high‐pressure or reactive fluids through talc‐rich lithologies.
Evaluating the Performance of the Canadian Land Surface Scheme Including Biogeochemical Cycles (CLASSIC) Tailored to the Pan‐Canadian Domain
Authors: Curasi Salvatore R. , Melton Joe R. , Humphreys Elyn R. , Wang Libo , Seiler Christian , Cannon Alex J. , Chan Ed , Qu Bo 
Published: April 2023

AbstractCanada's boreal forests and tundra ecosystems are responding to unprecedented climate change with implications for the global carbon (C) cycle and global climate. However, our ability to model the response of Canada's terrestrial ecosystems to climate change is limited and there has been no comprehensive, process‐based assessment of Canada's terrestrial C cycle. We tailor the Canadian Land Surface Scheme Including Biogeochemical Cycles (CLASSIC) to Canada and evaluate its C cycling performance against independent reference data. We utilize skill scores to assess model performance against reference data alongside benchmark scores that quantify the level of agreement between the reference data sets to aid in interpretation. Our results demonstrate CLASSIC's sensitivity to prescribed vegetation cover. They also show that the addition of five region‐specific Plant functional types (PFTs) improves CLASSIC's skill at simulating the Canadian C cycle. CLASSIC performs well when tailored to Canada, falls within the range of the reference data sets, and meets or exceeds the benchmark scores for most C cycling processes. New region‐specific land cover products, well‐informed PFT parameterizations, and more detailed reference data sets will facilitate improvements to the representation of the terrestrial C cycle in regional and global land surface models. Incorporating a parameterization for boreal disturbance processes and explicitly representing peatlands and permafrost soils will improve CLASSIC's future performance in Canada and other boreal regions. This is an important step toward a comprehensive process‐based assessment of Canada's terrestrial C cycle and evaluating Canada's net C balance under climate change.
Cassini Radio Occultation Observations of Saturn's Ionosphere: Electron Density Profiles From 2005 to 2013
Authors: Tamburo P. , Withers Paul , Dalba P. A. , Moore L. , Koskinen T. 
Published: April 2023

AbstractA set of electron density profiles of Saturn's ionosphere acquired by Cassini radio occultations is archived at the NASA Planetary Data System. However, the reference surface that defines zero altitude in these profiles is unknown and appears to vary by 1,500 km at fixed latitude. These profiles are immensely valuable for addressing questions pertaining to the vertical structure, meridional structure, diurnal variations, or solar cycle dependence of Saturn's ionosphere, but their value is severely limited by their questionable altitude scales. Here we have resolved this problem by independently generating the set of 60 electron density profiles. These profiles confirm that, as noted by previous authors, the structure of Saturn's ionosphere is highly variable. Nevertheless, the profiles suggest an underlying morphology of a broad layer at relatively high altitude (often at approximately 2,000–3,000 km altitude) and a series of narrower layers at lower altitude (often at approximately 1,000 km altitude). The vertical structure of Saturn's ionosphere depends on latitude and local time. At low latitudes, densities are greater at dusk than at dawn. Conversely, at mid latitudes, densities are greater at dawn than at dusk. The plasma scale height of the topside ionosphere is relatively small at low latitudes. The high, broad ionospheric layer is apparent at mid and high latitudes at both dawn and dusk, but is not present at low latitudes at either dawn or dusk. Total electron content also shows a strong dependence on latitude, with high latitudes having greater values than low and mid latitudes.
Construction of multiple concentration gradients for single-cell level drug screening
Authors: Shen Shaofei , Zhang Fangjuan , Zhang Yali , Li Yi , Niu Yanbing , Pang Long , Wang Jinyi 
Published: April 2023

AbstractIsolation and manipulation of single cells play a crucial role in drug screening. However, previously reported single-cell drug screening lacked multiple-dose concentration gradient studies, which limits their ability to predict drug performance accurately. To solve this problem, we constructed a multiconcentration gradient generator in which a Tai Chi-spiral mixer can accelerate solution mixing in a short time and produce a linear concentration gradient. Later, a gradient generator combined with a single-cell capture array was adopted to investigate the effects of single or combined doses of 5-fluorouracil and cisplatin on human hepatoma cells and human breast carcinoma cells (at the single-cell level). The results showed that both drugs were effective in inhibiting the growth of cancer cells, and the combination was more effective for human hepatoma cells. In addition, the relationship between the biomechanical heterogeneity (e.g., deformability and size) of tumor cells and potential drug resistance at the single-cell level was investigated, indicating that small and/or deformable cells were more resistant than large and/or less deformable cells. The device provides a simple and reliable platform for studying the optimal dosage of different drug candidates at the single-cell level and effectively screening single-agent chemotherapy regimens and combination therapies.
Inhibition of USP14 promotes TNFα-induced cell death in head and neck squamous cell carcinoma (HNSCC)
Authors: Morgan Ethan L. , Toni Tiffany , Viswanathan Ramya , Robbins Yvette , Yang Xinping , Cheng Hui , Gunti Sreenivasulu , Huynh Angel , Sowers Anastasia L. , Mitchell James B. , Allen Clint T. , Chen Zhong , Van Waes Carter 
Published: April 2023

AbstractTNFα is a key mediator of immune, chemotherapy and radiotherapy-induced cytotoxicity, but several cancers, including head and neck squamous cell carcinomas (HNSCC), display resistance to TNFα due to activation of the canonical NFκB pro-survival pathway. However, direct targeting of this pathway is associated with significant toxicity; thus, it is vital to identify novel mechanism(s) contributing to NFκB activation and TNFα resistance in cancer cells. Here, we demonstrate that the expression of proteasome-associated deubiquitinase USP14 is significantly increased in HNSCC and correlates with worse progression free survival in Human Papillomavirus (HPV)- HNSCC. Inhibition or depletion of USP14 inhibited the proliferation and survival of HNSCC cells. Further, USP14 inhibition reduced both basal and TNFα-inducible NFκB activity, NFκB-dependent gene expression and the nuclear translocation of the NFκB subunit RELA. Mechanistically, USP14 bound to both RELA and IκBα and reduced IκBα K48-ubiquitination leading to the degradation of IκBα, a critical inhibitor of the canonical NFκB pathway. Furthermore, we demonstrated that b-AP15, an inhibitor of USP14 and UCHL5, sensitized HNSCC cells to TNFα-mediated cell death, as well as radiation-induced cell death in vitro. Finally, b-AP15 delayed tumor growth and enhanced survival, both as a monotherapy and in combination with radiation, in HNSCC tumor xenograft models in vivo, which could be significantly attenuated by TNFα depletion. These data offer new insights into the activation of NFκB signaling in HNSCC and demonstrate that small molecule inhibitors targeting the ubiquitin pathway warrant further investigation as a novel therapeutic avenue to sensitize these cancers to TNFα- and radiation-induced cytotoxicity.
Galectin-3 promotes secretion of proteases that decrease epithelium integrity in human colon cancer cells
Authors: Li Shun , Pritchard David Mark , Yu Lu-Gang 
Published: April 2023

AbstractGalectin-3 is a galactoside-binding protein that is commonly overexpressed in many epithelial cancers. It is increasingly recognized as a multi-functional, multi-mode promoter in cancer development, progression, and metastasis. This study reports that galectin-3 secretion by human colon cancer cells induces cancer cell secretion, in an autocrine/paracrine manner, of a number of proteases including cathepsin-B, MMP-1 and MMP-13. The secretion of these proteases causes disruption of epithelial monolayer integrity, increases its permeability and promotes tumour cell invasion. This effect of galectin-3 is shown to be mediated through induction of cellular PYK2-GSK3α/β signalling and can be prevented by the presence of galectin-3 binding inhibitors. This study thus reveals an important mechanism in galectin-3-mediated promotion of cancer progression and metastasis. It provides further evidence to the increased realization of galectin-3 as a potential therapeutic target for the treatment of cancer.
Previously uncharacterized rectangular bacterial structures in the dolphin mouth
Authors: Dudek Natasha K. , Galaz-Montoya Jesus G. , Shi Handuo , Mayer Megan , Danita Cristina , Celis Arianna I. , Viehboeck Tobias , Wu Gong-Her , Behr Barry , Bulgheresi Silvia , Huang Kerwyn Casey , Chiu Wah , Relman David A. 
Published: April 2023

AbstractMuch remains to be explored regarding the diversity of uncultured, host-associated microbes. Here, we describe rectangular bacterial structures (RBSs) in the mouths of bottlenose dolphins. DNA staining revealed multiple paired bands within RBSs, suggesting the presence of cells dividing along the longitudinal axis. Cryogenic transmission electron microscopy and tomography showed parallel membrane-bound segments that are likely cells, encapsulated by an S-layer-like periodic surface covering. RBSs displayed unusual pilus-like appendages with bundles of threads splayed at the tips. We present multiple lines of evidence, including genomic DNA sequencing of micromanipulated RBSs, 16S rRNA gene sequencing, and fluorescence in situ hybridization, suggesting that RBSs are bacterial and distinct from the genera Simonsiella and Conchiformibius (family Neisseriaceae), with which they share similar morphology and division patterning. Our findings highlight the diversity of novel microbial forms and lifestyles that await characterization using tools complementary to genomics such as microscopy.
Vibrio cholerae biofilms use modular adhesins with glycan-targeting and nonspecific surface binding domains for colonization
Authors: Huang Xin , Nero Thomas , Weerasekera Ranjuna , Matej Katherine H. , Hinbest Alex , Jiang Zhaowei , Lee Rebecca F. , Wu Longjun , Chak Cecilia , Nijjer Japinder , Gibaldi Isabella , Yang Hang , Gamble Nathan , Ng Wai-Leung , Malaker Stacy A. , Sumigray Kaelyn , Olson Rich , Yan Jing 
Published: April 2023

AbstractBacterial biofilms are formed on environmental surfaces and host tissues, and facilitate host colonization and antibiotic resistance by human pathogens. Bacteria often express multiple adhesive proteins (adhesins), but it is often unclear whether adhesins have specialized or redundant roles. Here, we show how the model biofilm-forming organism Vibrio cholerae uses two adhesins with overlapping but distinct functions to achieve robust adhesion to diverse surfaces. Both biofilm-specific adhesins Bap1 and RbmC function as a “double-sided tape”: they share a β-propeller domain that binds to the biofilm matrix exopolysaccharide, but have distinct environment-facing domains. Bap1 adheres to lipids and abiotic surfaces, while RbmC mainly mediates binding to host surfaces. Furthermore, both adhesins contribute to adhesion in an enteroid monolayer colonization model. We expect that similar modular domains may be utilized by other pathogens, and this line of research can potentially lead to new biofilm-removal strategies and biofilm-inspired adhesives.
Electrochemistry-assisted selective butadiene hydrogenation with water
Authors: Yan Yong-Qing , Chen Ya , Wang Zhao , Chen Li-Hua , Tang Hao-Lin , Su Bao-Lian 
Published: April 2023

AbstractAlkene feedstocks are used to produce polymers with a market expected to reach 128.4 million metric tons by 2027. Butadiene is one of the impurities poisoning alkene polymerization catalysts and is usually removed by thermocatalytic selective hydrogenation. Excessive use of H2, poor alkene selectivity and high operating temperature (e.g. up to 350 °C) remain the most significant drawbacks of the thermocatalytic process, calling for innovative alternatives. Here we report a room-temperature (25~30 °C) electrochemistry-assisted selective hydrogenation process in a gas-fed fixed bed reactor, using water as the hydrogen source. Using a palladium membrane as the catalyst, this process offers a robust catalytic performance for selective butadiene hydrogenation, with alkene selectivity staying around 92% at a butadiene conversion above 97% for over 360 h of time on stream. The overall energy consumption of this process is 0.003 Wh/mLbutadiene, which is thousands of times lower than that of the thermocatalytic route. This study proposes an alternative electrochemical technology for industrial hydrogenation without the need for elevated temperature and hydrogen gas.
Non-solvent post-modifications with volatile reagents for remarkably porous ketone functionalized polymers of intrinsic microporosity
Authors: Wongwilawan Sirinapa , Nguyen Thien S. , Nguyen Thi Phuong Nga , Alhaji Abdulhadi , Lim Wonki , Hong Yeongran , Park Jin Su , Atilhan Mert , Kim Bumjoon J. , Eddaoudi Mohamed , Yavuz Cafer T. 
Published: April 2023

AbstractChemical modifications of porous materials almost always result in loss of structural integrity, porosity, solubility, or stability. Previous attempts, so far, have not allowed any promising trend to unravel, perhaps because of the complexity of porous network frameworks. But the soluble porous polymers, the polymers of intrinsic microporosity, provide an excellent platform to develop a universal strategy for effective modification of functional groups for current demands in advanced applications. Here, we report complete transformation of PIM-1 nitriles into four previously inaccessible functional groups – ketones, alcohols, imines, and hydrazones – in a single step using volatile reagents and through a counter-intuitive non-solvent approach that enables surface area preservation. The modifications are simple, scalable, reproducible, and give record surface areas for modified PIM-1s despite at times having to pass up to two consecutive post-synthetic transformations. This unconventional dual-mode strategy offers valuable directions for chemical modification of porous materials.
Non-functional ubiquitin C-terminal hydrolase L1 drives podocyte injury through impairing proteasomes in autoimmune glomerulonephritis
Authors: Reichelt Julia , Sachs Wiebke , Frömbling Sarah , Fehlert Julia , Studencka-Turski Maja , Betz Anna , Loreth Desiree , Blume Lukas , Witt Susanne , Pohl Sandra , Brand Johannes , Czesla Maire , Knop Jan , Florea Bogdan I. , Zielinski Stephanie , Sachs Marlies , Hoxha Elion , Hermans-Borgmeyer Irm , Zahner Gunther , Wiech Thorsten , Krüger Elke , Meyer-Schwesinger Catherine 
Published: April 2023

AbstractLittle is known about the mechanistic significance of the ubiquitin proteasome system (UPS) in a kidney autoimmune environment. In membranous nephropathy (MN), autoantibodies target podocytes of the glomerular filter resulting in proteinuria. Converging biochemical, structural, mouse pathomechanistic, and clinical information we report that the deubiquitinase Ubiquitin C-terminal hydrolase L1 (UCH-L1) is induced by oxidative stress in podocytes and is directly involved in proteasome substrate accumulation. Mechanistically, this toxic gain-of-function is mediated by non-functional UCH-L1, which interacts with and thereby impairs proteasomes. In experimental MN, UCH-L1 becomes non-functional and MN patients with poor outcome exhibit autoantibodies with preferential reactivity to non-functional UCH-L1. Podocyte-specific deletion of UCH-L1 protects from experimental MN, whereas overexpression of non-functional UCH-L1 impairs podocyte proteostasis and drives injury in mice. In conclusion, the UPS is pathomechanistically linked to podocyte disease by aberrant proteasomal interactions of non-functional UCH-L1.
Nucleocytoplasmic transport of active HER2 causes fractional escape from the DCIS-like state
Authors: Wang Lixin , Paudel B. Bishal , McKnight R. Anthony , Janes Kevin A. 
Published: April 2023

AbstractActivation of HER2/ErbB2 coincides with escape from ductal carcinoma in situ (DCIS) premalignancy and disrupts 3D organization of cultured breast-epithelial spheroids. The 3D phenotype is infrequent, however, and mechanisms for its incomplete penetrance have been elusive. Using inducible HER2/ErbB2–EGFR/ErbB1 heterodimers, we match phenotype penetrance to the frequency of co-occurring transcriptomic changes and uncover a reconfiguration in the karyopherin network regulating ErbB nucleocytoplasmic transport. Induction of the exportin CSE1L inhibits nuclear accumulation of ErbBs, whereas nuclear ErbBs silence the importin KPNA1 by inducing miR-205. When these negative feedbacks are incorporated into a validated systems model of nucleocytoplasmic transport, steady-state localization of ErbB cargo becomes ultrasensitive to initial CSE1L abundance. Erbb2-driven carcinomas with Cse1l deficiency outgrow less irregularly from mammary ducts, and NLS-attenuating mutants or variants of HER2 favor escape in 3D culture. We conclude here that adaptive nucleocytoplasmic relocalization of HER2 creates a systems-level molecular switch at the premalignant-to-malignant transition.
Dandelion uses the single-cell adaptive immune receptor repertoire to explore lymphocyte developmental origins
Authors: Suo Chenqu , Polanski Krzysztof , Dann Emma , Lindeboom Rik G. H. , Vilarrasa-Blasi Roser , Vento-Tormo Roser , Haniffa Muzlifah , Meyer Kerstin B. , Dratva Lisa M. , Tuong Zewen Kelvin , Clatworthy Menna R. , Teichmann Sarah A. 
Published: April 2023

AbstractAssessment of single-cell gene expression (single-cell RNA sequencing) and adaptive immune receptor (AIR) sequencing (scVDJ-seq) has been invaluable in studying lymphocyte biology. Here we introduce Dandelion, a computational pipeline for scVDJ-seq analysis. It enables the application of standard V(D)J analysis workflows to single-cell datasets, delivering improved V(D)J contig annotation and the identification of nonproductive and partially spliced contigs. We devised a strategy to create an AIR feature space that can be used for both differential V(D)J usage analysis and pseudotime trajectory inference. The application of Dandelion improved the alignment of human thymic development trajectories of double-positive T cells to mature single-positive CD4/CD8 T cells, generating predictions of factors regulating lineage commitment. Dandelion analysis of other cell compartments provided insights into the origins of human B1 cells and ILC/NK cell development, illustrating the power of our approach. Dandelion is available athttps://www.github.com/zktuong/dandelion.
Pan-cancer analysis reveals IGFL2 as a potential target for cancer prognosis and immunotherapy
Authors: Wang Yuqi , Yuan Hongwei , Yue Genquan , Zhao Lingyan , Xia Yuan , Zhang Nan , Li Hailing , Liu Dongyang , Su Yubo , Wang Haisheng , Gao Yumin 
Published: April 2023

AbstractInsulin-like growth factor like family member 2 (IGFL2) is a gene in the IGFL family, located on chromosome 19, whose role in cancer is unclear, and the aim of this study was to investigate the relevance of IGFL2 expression, prognosis, immunity, and mutation in pan-cancer. Obtaining information from The Cancer Genome Atlas and The Genotype-Tissue Expression Project (GTEx) databases for expression analysis and combining with The Gene Expression Profile Interaction Analysis database for prognostic aspects. Analysis of immune cell infiltration by TIMER and CIBERSORT algorithms. Calculation of correlation of immune-related genes with IGFL2 expression and tumor mutational burden and microsatellite instability. Mutations and DNA methylation were analyzed using the cBioPortal database and the UALCAN database, and functional enrichment was performed using Gene set enrichment analysis (GSEA). IGFL2 expression is significantly elevated in tumor tissue and high expression has a worse prognosis in most cancers. In immune correlation analysis, it was associated with most immune cells and immune-related genes. In most cancers, IGFL2 methylation is lower and the group with mutations in IGFL2 has a worse prognosis than the normal group. The GSEA analysis showed that IGFL2 was significantly enriched in signaling and metabolism. IGFL2 may be involved in the development of many types of cancer, influencing the course of cancer with different biological functions. It may also be a biomarker for tumor immunotherapy.
EU climate action through an energy poverty lens
Authors: Vandyck Toon , Della Valle Nives , Temursho Umed , Weitzel Matthias 
Published: April 2023

AbstractCarbon pricing can steer energy choices towards low-carbon fuels and foster energy conservation efforts. Simultaneously, higher fossil fuel prices may exacerbate energy poverty. A just portfolio of climate policies therefore requires a balanced instrument mix to jointly combat climate change and energy poverty. We review recent policy developments in the EU aimed at addressing energy poverty and the social implications of the climate neutrality transition. We then operationalise an affordability-based definition of energy poverty and numerically illustrate that recent EU climate policy proposals risk raising the number of energy poor when not accompanied with complementary measures, while alternative climate policy designs could lift more than 1 million households out of energy poverty through income-targeted revenue recycling schemes. While these schemes have low informational requirements and appear sufficient to avoid exacerbating energy poverty, the findings suggest that more tailored interventions are needed. Finally, we discuss how insights from behavioural economics and energy justice can help shape optimal policy packages and processes.