bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transport and Weathering of Large Limestone Blocks on Hillslopes in Heterolithic Sedimentary Landscapes
Authors: McCarroll Nicholas R. , Temme Arnaud J. A. M. 
Published: September 2022

AbstractGeomorphic transport laws that describe the movement of material across landscapes generally hide the role of lithological and climatic boundary conditions behind proportionality terms. The geomorphic community aims to characterize the role of these boundary conditions and include them in mechanistic transport laws. A more detailed mechanistic understanding is needed for hillslopes formed in heterolithic rock that weathers into weak regolith and hard blocks, such as in hogbacks. The properties of such blocks may determine both the process and rate of their transport downslope. We focused on soil mantled hillslopes in the Flint Hills of Kansas in the United States, where we studied the role of block shape and size under a limestone cliff that breaks up approximately into equal amounts of cubic and tile‐shaped clasts. Based on previous studies on the transport of rock clasts, we hypothesized that cubic and tile‐shaped blocks should be transported differently, leading to different distributions of size and orientation with increasing distance from the cliff. Block shape does have significant influence over how soil collects and is stored on the hillslope near blocks. Yet, few cubic blocks appear to be transported through tumbling in contrast with assumptions in recent modeling work. We found complex relationships between block size and distance from the cliff face and we propose that this is due to weathering via fragmentation. This process produces discrete smaller fragments from a larger parent block. We suggest that at least in Kansas both cubic and tile‐shaped blocks are transported primarily by creep processes.
SMYD3 promotes aerobic glycolysis in diffuse large B-cell lymphoma via H3K4me3-mediated PKM2 transcription
Authors: Tian Tian , Li Jiwei , Shi Di , Zeng Yupeng , Yu Baohua , Li Xiaoqiu , Wei Ping , Zhou Xiaoyan 
Published: September 2022

AbstractGenetic abnormalities in histone methyltransferases (HMTs) frequently occur in diffuse large B-cell lymphoma (DLBCL) and are related to its progression. SET and MYND domain containing 3 (SMYD3) is an HMT that is upregulated in various tumors and promotes their malignancy. However, to the best of our knowledge, the function of SMYD3 in DLBCL has not been investigated thus far. In the present study, 22 HMT genes related to cancer development were first selected according to current literature, and it was found that high SMYD3 expression was significantly associated with poor progression-free survival in patients with DLBCL. SMYD3 protein levels were upregulated and positively associated with poor prognosis and poor responsiveness to chemotherapy in patients with DLBCL. Functional examinations demonstrated that SMYD3 increased cell proliferation and the flux of aerobic glycolysis in DLBCL cells in vitro and in vivo and decreased cell sensitivity to doxorubicin in vitro. Moreover, SMYD3 could directly bind to specific sequences of Pyruvate Kinase M2 (PKM2) and promote DLBCL cell proliferation and aerobic glycolysis via H3K4me3-mediated PKM2 transcription. Clinically, SMYD3 expression positively correlated with that of PKM2, and high SMYD3 was significantly associated with high maximum standardized uptake value (SUVmax) detected by [(18)F]-fluorodeoxyglucose ((18)F-FDG) PET/computed tomography (PET/CT) in DLBCL samples. Concomitant expression of SMYD3 and PKM2 positively correlated with poor progression-free and overall survival in patients with DLBCL and may serve as novel biomarkers in DLBCL.
Disulfiram alleviates pristane-induced lupus via inhibiting GSDMD-mediated pyroptosis
Authors: Zhuang Lili , Luo Xiaoqing , Wu Shufan , Lin Zhangmei , Zhang Yanan , Zhai Zeqing , Yang Fangyuan , Li Yehao , Zhuang Jian , Luo Guihu , Xu Wenchao , He Yi , Sun Erwei 
Published: September 2022

AbstractActivation of multiple inflammasomes in monocytes/macrophages is associated with the pathogenesis of systemic lupus erythematosus (SLE). Gasdermin D (GSDMD)-mediated pyroptosis, a common consequence of multiple activated inflammasomes, is a programmed cell death with strong inflammatory responses. This suggested that targeting monocyte/macrophage pyroptosis might provide an opportunity to cure SLE. Here, we aimed to investigate the effect of disulfiram (DSF), a small molecule inhibitor of pyroptosis, and its potential therapeutic mechanism for SLE. The mRNA expression of GSDMD and IL-1β were significantly increased in peripheral blood mononuclear cells (PBMCs) from SLE patients. Importantly, we found serum from SLE patients rather than healthy controls induced GSDMD-mediated pyroptosis in THP-1 cells, as evidenced by enhanced LDH release, increased number of PI-positive cells, and high expression of full-length GSDMD and N-terminal GSDMD. Interestingly, treatment with DSF obviously inhibited pyroptosis of THP-1 cells induced by serum from SLE patients. Of note, DSF administration reduced proteinuria, serum anti-dsDNA level, and renal immune complex. It also attenuated renal damage in PIL mice. Further research found that the high level of serum IL-β and GSDMD-mediated pyroptosis of glomerular macrophages in PIL mice were rescued with DSF treatment. These data implied that GSDMD-mediated monocytes/macrophages pyroptosis played an important role in the pathogenesis of SLE and DSF might be a potential alternative therapeutic agent for SLE.
Approaching discussions about genetics with palliative patients and their families: a qualitative exploration with genetic health professionals
Authors: White Stephanie , Turbitt Erin , Phillips Jane L. , Jacobs Chris 
Published: September 2022

AbstractGenetic information can provide clinical benefits to families of palliative patients. However, integration of genetics into mainstream medicine has not focused on palliative populations. We explored the views and experiences of genetic health professionals in addressing genetics with palliative patients, and their families. We conducted an interpretive descriptive qualitative study with genetic counsellors and clinical geneticists using interviews and focus groups. Findings were generated using reflexive thematic analysis. Three themes were identified: (1) Focusing on the benefit to the family, (2) The discomfort of addressing genetics near end-of-life and (3) “It’s always on the back-burner”: Challenges to getting genetics on the palliative care agenda. Participants discussed the familial benefit of genetics in palliative care alongside the challenges when patients are near end-of-life. They perceived genetics as low priority for palliative care due to misunderstandings related to the value of genetic information. Acknowledging the challenges in the palliative care context, genetic health professionals want improved service leadership and awareness of the familial benefits of palliative genetic testing. Strong leadership to support genetic health professionals in addressing these barriers is needed for the benefits of genetic information to be realised.
Distinct ankyrin repeat subdomains control VAPYRIN locations and intracellular accommodation functions during arbuscular mycorrhizal symbiosis
Authors: Lindsay Penelope L. , Ivanov Sergey , Pumplin Nathan , Zhang Xinchun , Harrison Maria J. 
Published: September 2022

AbstractOver 70% of vascular flowering plants engage in endosymbiotic associations with arbuscular mycorrhizal (AM) fungi. VAPYRIN (VPY) is a plant protein that is required for intracellular accommodation of AM fungi but how it functions is still unclear. VPY has a large ankyrin repeat domain with potential for interactions with multiple proteins. Here we show that overexpression of the ankyrin repeat domain results in a vpy-like phenotype, consistent with the sequestration of interacting proteins. We identify distinct ankyrin repeats that are essential for intracellular accommodation of arbuscules and reveal that VPY functions in both the cytoplasm and nucleus. VPY interacts with two kinases, including DOES NOT MAKE INFECTIONS3 (DMI3), a nuclear-localized symbiosis signaling kinase. Overexpression of VPY in a symbiosis-attenuated genetic background results in a dmi3 -like phenotype suggesting that VPY negatively influences DMI3 function. Overall, the data indicate a requirement for VPY in the nucleus and cytoplasm where it may coordinate signaling and cellular accommodation processes.
HIF-1 stabilization in T cells hampers the control of Mycobacterium tuberculosis infection
Authors: Liu Ruining , Muliadi Victoria , Mou Wenjun , Li Hanxiong , Yuan Juan , Holmberg Johan , Chambers Benedict J. , Ullah Nadeem , Wurth Jakob , Alzrigat Mohammad , Schlisio Susanne , Carow Berit , Larsson Lars Gunnar , Rottenberg Martin E. 
Published: September 2022

AbstractThe hypoxia-inducible factors (HIFs) regulate the main transcriptional pathway of response to hypoxia in T cells and are negatively regulated by von Hippel-Lindau factor (VHL). But the role of HIFs in the regulation of CD4 T cell responses during infection withM. tuberculosisisn’t well understood. Here we show that mice lacking VHL in T cells (Vhl cKO) are highly susceptible to infection withM. tuberculosis, which is associated with a low accumulation of mycobacteria-specific T cells in the lungs that display reduced proliferation, altered differentiation and enhanced expression of inhibitory receptors. In contrast, HIF-1 deficiency in T cells is redundant forM. tuberculosiscontrol.Vhl cKOmice also show reduced responses to vaccination. Further, VHL promotes proper MYC-activation, cell-growth responses, DNA synthesis, proliferation and survival of CD4 T cells after TCR activation. The VHL-deficient T cell responses are rescued by the loss of HIF-1α, indicating that the increased susceptibility toM. tuberculosisinfection and the impaired responses ofVhl-deficient T cells are HIF-1-dependent.
Augmented tactile-perception and haptic-feedback rings as human-machine interfaces aiming for immersive interactions
Authors: Sun Zhongda , Zhu Minglu , Shan Xuechuan , Lee Chengkuo 
Published: September 2022

AbstractAdvancements of virtual reality technology pave the way for developing wearable devices to enable somatosensory sensation, which can bring more comprehensive perception and feedback in the metaverse-based virtual society. Here, we propose augmented tactile-perception and haptic-feedback rings with multimodal sensing and feedback capabilities. This highly integrated ring consists of triboelectric and pyroelectric sensors for tactile and temperature perception, and vibrators and nichrome heaters for vibro- and thermo-haptic feedback. All these components integrated on the ring can be directly driven by a custom wireless platform of low power consumption for wearable/portable scenarios. With voltage integration processing, high-resolution continuous finger motion tracking is achieved via the triboelectric tactile sensor, which also contributes to superior performance in gesture/object recognition with artificial intelligence analysis. By fusing the multimodal sensing and feedback functions, an interactive metaverse platform with cross-space perception capability is successfully achieved, giving people a face-to-face like immersive virtual social experience.
Allosteric inhibition of HTRA1 activity by a conformational lock mechanism to treat age-related macular degeneration
Authors: Gerhardy Stefan , Ultsch Mark , Tang Wanjian , Green Evan , Holden Jeffrey K. , Li Wei , Estevez Alberto , Arthur Chris , Tom Irene , Rohou Alexis , Kirchhofer Daniel 
Published: September 2022

AbstractThe trimeric serine protease HTRA1 is a genetic risk factor associated with geographic atrophy (GA), a currently untreatable form of age-related macular degeneration. Here, we describe the allosteric inhibition mechanism of HTRA1 by a clinical Fab fragment, currently being evaluated for GA treatment. Using cryo-EM, X-ray crystallography and biochemical assays we identify the exposed LoopA of HTRA1 as the sole Fab epitope, which is approximately 30 Å away from the active site. The cryo-EM structure of the HTRA1:Fab complex in combination with molecular dynamics simulations revealed that Fab binding to LoopA locks HTRA1 in a non-competent conformational state, incapable of supporting catalysis. Moreover, grafting the HTRA1-LoopA epitope onto HTRA2 and HTRA3 transferred the allosteric inhibition mechanism. This suggests a conserved conformational lock mechanism across the HTRA family and a critical role of LoopA for catalysis, which was supported by the reduced activity of HTRA1-3 upon LoopA deletion or perturbation. This study reveals the long-range inhibition mechanism of the clinical Fab and identifies an essential function of the exposed LoopA for activity of HTRA family proteases.
The human thalamus orchestrates neocortical oscillations during NREM sleep
Authors: Schreiner Thomas , Kaufmann Elisabeth , Noachtar Soheyl , Mehrkens Jan-Hinnerk , Staudigl Tobias 
Published: September 2022

AbstractA hallmark of non-rapid eye movement sleep is the coordinated interplay of slow oscillations (SOs) and sleep spindles. Traditionally, a cortico-thalamo-cortical loop is suggested to coordinate these rhythms: neocortically-generated SOs trigger spindles in the thalamus that are projected back to neocortex. Here, we used intrathalamic recordings from human epilepsy patients to test this canonical interplay. We show that SOs in the anterior thalamus precede neocortical SOs (peak −50 ms), whereas concurrently-recorded SOs in the mediodorsal thalamus are led by neocortical SOs (peak +50 ms). Sleep spindles, detected in both thalamic nuclei, preceded their neocortical counterparts (peak −100 ms) and were initiated during early phases of thalamic SOs. Our findings indicate an active role of the anterior thalamus in organizing sleep rhythms in the neocortex and highlight the functional diversity of thalamic nuclei in humans. The thalamic coordination of sleep oscillations could have broad implications for the mechanisms underlying memory consolidation.
X-ray crystallographic characterization of the SARS-CoV-2 main protease polyprotein cleavage sites essential for viral processing and maturation
Authors: Lee Jaeyong , Kenward Calem , Worrall Liam J. , Vuckovic Marija , Gentile Francesco , Ton Anh-Tien , Ng Myles , Cherkasov Artem , Strynadka Natalie C. J. , Paetzel Mark 
Published: September 2022

AbstractSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the pathogen that causes COVID-19, produces polyproteins 1a and 1ab that contain, respectively, 11 or 16 non-structural proteins (nsp). Nsp5 is the main protease (Mpro) responsible for cleavage at eleven positions along these polyproteins, including at its own N- and C-terminal boundaries, representing essential processing events for viral assembly and maturation. Using C-terminally substituted Mpro chimeras, we have determined X-ray crystallographic structures of Mpro in complex with 10 of its 11 viral cleavage sites, bound at full occupancy intermolecularly in trans, within the active site of either the native enzyme and/or a catalytic mutant (C145A). Capture of both acyl-enzyme intermediate and product-like complex forms of a P2(Leu) substrate in the native active site provides direct comparative characterization of these mechanistic steps as well as further informs the basis for enhanced product release of Mpro’s own unique C-terminal P2(Phe) cleavage site to prevent autoinhibition. We characterize the underlying noncovalent interactions governing binding and specificity for this diverse set of substrates, showing remarkable plasticity for subsites beyond the anchoring P1(Gln)-P2(Leu/Val/Phe), representing together a near complete analysis of a multiprocessing viral protease. Collectively, these crystallographic snapshots provide valuable mechanistic and structural insights for antiviral therapeutic development.
The TFEB-TGIF1 axis regulates EMT in mouse epicardial cells
Authors: Astanina Elena , Doronzo Gabriella , Corà Davide , Neri Francesco , Oliviero Salvatore , Genova Tullio , Mussano Federico , Middonti Emanuele , Vallariello Edoardo , Cencioni Chiara , Valdembri Donatella , Serini Guido , Limana Federica , Foglio Eleonora , Ballabio Andrea , Bussolino Federico 
Published: September 2022

AbstractEpithelial-mesenchymal transition (EMT) is a complex and pivotal process involved in organogenesis and is related to several pathological processes, including cancer and fibrosis. During heart development, EMT mediates the conversion of epicardial cells into vascular smooth muscle cells and cardiac interstitial fibroblasts. Here, we show that the oncogenic transcription factor EB (TFEB) is a key regulator of EMT in epicardial cells and that its genetic overexpression in mouse epicardium is lethal due to heart defects linked to impaired EMT. TFEB specifically orchestrates the EMT-promoting function of transforming growth factor (TGF) β, and this effect results from activated transcription of thymine-guanine-interacting factor (TGIF)1, a TGFβ/Smad pathway repressor. TheTgif1promoter is activated by TFEB, and in vitro and in vivo findings demonstrate its increased expression whenTfebis overexpressed. Furthermore,Tfeboverexpression in vitro prevents TGFβ-induced EMT, and this effect is abolished byTgif1silencing.Tfebloss of function, similar to that ofTgif1, sensitizes cells to TGFβ, inducing an EMT response to low doses of TGFβ. Together, our findings reveal an unexpected function of TFEB in regulating EMT, which might provide insights into injured heart repair and control of cancer progression.
The nucleolus is the site for inflammatory RNA decay during infection
Authors: Lee Taeyun A. , Han Heonjong , Polash Ahsan , Cho Seok Keun , Lee Ji Won , Ra Eun A. , Lee Eunhye , Park Areum , Kang Sujin , Choi Junhee L. , Kim Ji Hyun , Lee Ji Eun , Min Kyung-Won , Yang Seong Wook , Hafner Markus , Lee Insuk , Yoon Je-Hyun , Lee Sungwook , Park Boyoun 
Published: September 2022

AbstractInflammatory cytokines are key signaling molecules that can promote an immune response, thus their RNA turnover must be tightly controlled during infection. Most studies investigate the RNA decay pathways in the cytosol or nucleoplasm but never focused on the nucleolus. Although this organelle has well-studied roles in ribosome biogenesis and cellular stress sensing, the mechanism of RNA decay within the nucleolus is not completely understood. Here, we report that the nucleolus is an essential site of inflammatory pre-mRNA instability during infection. RNA-sequencing analysis reveals that not only do inflammatory genes have higher intronic read densities compared with non-inflammatory genes, but their pre-mRNAs are highly enriched in nucleoli during infection. Notably, nucleolin (NCL) acts as a guide factor for recruiting cytosine or uracil (C/U)-rich sequence-containing inflammatory pre-mRNAs and the Rrp6-exosome complex to the nucleolus through a physical interaction, thereby enabling targeted RNA delivery to Rrp6-exosomes and subsequent degradation. Consequently, Ncl depletion causes aberrant hyperinflammation, resulting in a severe lethality in response to LPS. Importantly, the dynamics of NCL post-translational modifications determine its functional activity in phases of LPS. This process represents a nucleolus-dependent pathway for maintaining inflammatory gene expression integrity and immunological homeostasis during infection.
Rhodium nanocrystals on porous graphdiyne for electrocatalytic hydrogen evolution from saline water
Authors: Gao Yang , Xue Yurui , Qi Lu , Xing Chengyu , Zheng Xuchen , He Feng , Li Yuliang 
Published: September 2022

AbstractThe realization of the efficient hydrogen conversion with large current densities at low overpotentials represents the development trend of this field. Here we report the atomic active sites tailoring through a facile synthetic method to yield well-defined Rhodium nanocrystals in aqueous solution using formic acid as the reducing agent and graphdiyne as the stabilizing support. High-resolution high-angle annular dark-field scanning-transmission electron microscopy images show the high-density atomic steps on the faces of hexahedral Rh nanocrystals. Experimental results reveal the formation of stablesp–C~Rh bonds can stabilize Rh nanocrystals and further improve charge transfer ability in the system. Experimental and density functional theory calculation results solidly demonstrate the exposed high active stepped surfaces and various metal atomic sites affect the electronic structure of the catalyst to reduce the overpotential resulting in the large-current hydrogen production from saline water. This exciting result demonstrates unmatched electrocatalytic performance and highly stable saline water electrolysis.
Spin-selected electron transfer in liquid–solid contact electrification
Authors: Lin Shiquan , Zhu Laipan , Tang Zhen , Wang Zhong Lin 
Published: September 2022

AbstractElectron transfer has been proven the dominant charge carrier during contact electrification at the liquid–solid interface. However, the effect of electron spin in contact electrification remains to be investigated. This study examines the charge transfer between different liquids and ferrimagnetic solids in a magnetic field, focusing on the contribution of O2 molecules to the liquid–solid contact electrification. The findings reveal that magnetic fields promote electron transfer at the O2-containing liquid–solid interfaces. Moreover, magnetic field-induced electron transfer increases at higher O2 concentrations in the liquids and decreases at elevated temperatures. The results indicate spin-selected electron transfer at liquid–solid interface. External magnetic fields can modulate the spin conversion of the radical pairs at the O2-containing liquid and ferrimagnetic solid interfaces due to the Zeeman interaction, promoting electron transfer. A spin-selected electron transfer model for liquid–solid contact electrification is further proposed based on the radical pair mechanism, in which the HO2 molecules and the free unpaired electrons from the ferrimagnetic solids are considered radical pairs. The spin conversion of the [HO2• •e−] pairs is affected by magnetic fields, rendering the electron transfer magnetic field-sensitive.
Organometallic complexation phenomenon observed during the natural aging of polyester urethane in the presence of iron corrosion
Authors: Lotz Hélène , Gasperuzzo Giulia , Gómez-Sánchez Elena 
Published: September 2022

AbstractShoes with polyester urethane soles have been stored for 3 decades in a museum environment after several months of mining use. Upon observation of sole material ageing under natural conditions, the shoes were laboratory stored since 2017 in order to evidence and follow signs of polyester urethane degradation. This study aims at characterizing a complex degradation material found on several shoes of the museum’s collection. Combining chemical composition analysis (EDX), mass spectroscopy (EGA-MS, py-GCMS) and vibrational spectroscopy (Raman and IR), results evidence the presence of iron carboxylates in different coordination modes. This study highlights the formation of a hitherto unknown degradation material of polyester urethane: an organometallic complex with iron ions coordinated with carboxylic rests of polyester polyol chains. The compound arises from the interaction between iron ions from the corrosion of structural metallic elements of the sole, and the polyester polyol fragments from the hydrolysis of the polyester urethane.