bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioinspired mechanical mineralization of organogels
Authors: Ayarza Jorge , Wang Jun , Kim Hojin , Huang Pin-Ruei , Cassaidy Britteny , Yan Gangbin , Liu Chong , Jaeger Heinrich M. , Rowan Stuart J. , Esser-Kahn Aaron P. 
Published: December 2023

AbstractMineralization is a long-lasting method commonly used by biological materials to selectively strengthen in response to site specific mechanical stress. Achieving a similar form of toughening in synthetic polymer composites remains challenging. In previous work, we developed methods to promote chemical reactions via the piezoelectrochemical effect with mechanical responses of inorganic, ZnO nanoparticles. Herein, we report a distinct example of a mechanically-mediated reaction in which the spherical ZnO nanoparticles react themselves leading to the formation of microrods composed of a Zn/S mineral inside an organogel. The microrods can be used to selectively create mineral deposits within the material resulting in the strengthening of the overall resulting composite.
Molecular basis and cellular functions of vinculin-actin directional catch bonding
Authors: Chirasani Venkat R. , Khan Mohammad Ashhar I. , Malavade Juilee N. , Dokholyan Nikolay V. , Hoffman Brenton D. , Campbell Sharon L. 
Published: December 2023

AbstractThe ability of cells and tissues to respond differentially to mechanical forces applied in distinct directions is mediated by the ability of load-bearing proteins to preferentially maintain physical linkages in certain directions. However, the molecular basis and biological consequences of directional force-sensitive binding remain unclear. Vinculin (Vcn) is a load-bearing linker protein that exhibits directional catch bonding due to interactions between the Vcn tail domain (Vt) and filamentous (F)-actin. We developed a computational approach to predict Vcn residues involved in directional catch bonding and produced a set of associated Vcn variants with unaltered Vt structure, actin binding, or phospholipid interactions. Incorporation of the variants did not affect Vcn activation but reduced Vcn loading and altered exchange dynamics, consistent with the loss of directional catch bonding. Expression of Vcn variants perturbed the coordination of subcellular structures and cell migration, establishing key cellular functions for Vcn directional catch bonding.
The bacterial replication origin BUS promotes nucleobase capture
Authors: Pelliciari Simone , Bodet-Lefèvre Salomé , Fenyk Stepan , Stevens Daniel , Winterhalter Charles , Schramm Frederic D. , Pintar Sara , Burnham Daniel R. , Merces George , Richardson Tomas T. , Tashiro Yumiko , Hubbard Julia , Yardimci Hasan , Ilangovan Aravindan , Murray Heath 
Published: December 2023

AbstractGenome duplication is essential for the proliferation of cellular life and this process is generally initiated by dedicated replication proteins at chromosome origins. In bacteria, DNA replication is initiated by the ubiquitous DnaA protein, which assembles into an oligomeric complex at the chromosome origin (oriC) that engages both double-stranded DNA (dsDNA) and single-stranded DNA (ssDNA) to promote DNA duplex opening. However, the mechanism of DnaA specifically opening a replication origin was unknown. Here we show that Bacillus subtilis DnaAATP assembles into a continuous oligomer at the site of DNA melting, extending from a dsDNA anchor to engage a single DNA strand. Within this complex, two nucleobases of each ssDNA binding motif (DnaA-trio) are captured within a dinucleotide binding pocket created by adjacent DnaA proteins. These results provide a molecular basis for DnaA specifically engaging the conserved sequence elements within the bacterial chromosome origin basal unwinding system (BUS).
Profiling ubiquitin signalling with UBIMAX reveals DNA damage- and SCFβ-Trcp1-dependent ubiquitylation of the actin-organizing protein Dbn1
Authors: Colding-Christensen Camilla S. , Kakulidis Ellen S. , Arroyo-Gomez Javier , Hendriks Ivo A. , Arkinson Connor , Fábián Zita , Gambus Agnieszka , Mailand Niels , Duxin Julien P. , Nielsen Michael L. 
Published: December 2023

AbstractUbiquitin widely modifies proteins, thereby regulating most cellular functions. The complexity of ubiquitin signalling necessitates unbiased methods enabling global detection of dynamic protein ubiquitylation. Here, we describe UBIMAX (UBiquitin target Identification by Mass spectrometry in Xenopus egg extracts), which enriches ubiquitin-conjugated proteins and quantifies regulation of protein ubiquitylation under precise and adaptable conditions. We benchmark UBIMAX by investigating DNA double-strand break-responsive ubiquitylation events, identifying previously known targets and revealing the actin-organizing protein Dbn1 as a major target of DNA damage-induced ubiquitylation. We find that Dbn1 is targeted for proteasomal degradation by the SCFβ-Trcp1 ubiquitin ligase, in a conserved mechanism driven by ATM-mediated phosphorylation of a previously uncharacterized β-Trcp1 degron containing an SQ motif. We further show that this degron is sufficient to induce DNA damage-dependent protein degradation of a model substrate. Collectively, we demonstrate UBIMAX’s ability to identify targets of stimulus-regulated ubiquitylation and reveal an SCFβ-Trcp1-mediated ubiquitylation mechanism controlled directly by the apical DNA damage response kinases.
Polygenic risk alters the penetrance of monogenic kidney disease
Authors: Khan Atlas , Shang Ning , Nestor Jordan G. , Weng Chunhua , Hripcsak George , Harris Peter C. , Gharavi Ali G. , Kiryluk Krzysztof 
Published: December 2023

AbstractChronic kidney disease (CKD) is determined by an interplay of monogenic, polygenic, and environmental risks. Autosomal dominant polycystic kidney disease (ADPKD) and COL4A-associated nephropathy (COL4A-AN) represent the most common forms of monogenic kidney diseases. These disorders have incomplete penetrance and variable expressivity, and we hypothesize that polygenic factors explain some of this variability. By combining SNP array, exome/genome sequence, and electronic health record data from the UK Biobank and All-of-Us cohorts, we demonstrate that the genome-wide polygenic score (GPS) significantly predicts CKD among ADPKD monogenic variant carriers. Compared to the middle tertile of the GPS for noncarriers, ADPKD variant carriers in the top tertile have a 54-fold increased risk of CKD, while ADPKD variant carriers in the bottom tertile have only a 3-fold increased risk of CKD. Similarly, the GPS significantly predicts CKD in COL4A-AN carriers. The carriers in the top tertile of the GPS have a 2.5-fold higher risk of CKD, while the risk for carriers in the bottom tertile is not different from the average population risk. These results suggest that accounting for polygenic risk improves risk stratification in monogenic kidney disease.
Atherosclerotic plaque development in mice is enhanced by myeloid ZEB1 downregulation
Authors: Martinez-Campanario M. C. , Cortés Marlies , Moreno-Lanceta Alazne , Han Lu , Ninfali Chiara , Domínguez Verónica , Andrés-Manzano María J. , Farràs Marta , Esteve-Codina Anna , Enrich Carlos , Díaz-Crespo Francisco J. , Pintado Belén , Escolà-Gil Joan C. , García de Frutos Pablo , Andrés Vicente , Melgar-Lesmes Pedro , Postigo Antonio 
Published: December 2023

AbstractAccumulation of lipid-laden macrophages within the arterial neointima is a critical step in atherosclerotic plaque formation. Here, we show that reduced levels of the cellular plasticity factor ZEB1 in macrophages increase atherosclerotic plaque formation and the chance of cardiovascular events. Compared to control counterparts (Zeb1WT/ApoeKO), male mice with Zeb1 ablation in their myeloid cells (Zeb1∆M/ApoeKO) have larger atherosclerotic plaques and higher lipid accumulation in their macrophages due to delayed lipid traffic and deficient cholesterol efflux. Zeb1∆M/ApoeKO mice display more pronounced systemic metabolic alterations than Zeb1WT/ApoeKO mice, with higher serum levels of low-density lipoproteins and inflammatory cytokines and larger ectopic fat deposits. Higher lipid accumulation in Zeb1∆M macrophages is reverted by the exogenous expression of Zeb1 through macrophage-targeted nanoparticles. In vivo administration of these nanoparticles reduces atherosclerotic plaque formation in Zeb1∆M/ApoeKO mice. Finally, low ZEB1 expression in human endarterectomies is associated with plaque rupture and cardiovascular events. These results set ZEB1 in macrophages as a potential target in the treatment of atherosclerosis.
Proximity extracellular protein-protein interaction analysis of EGFR using AirID-conjugated fragment of antigen binding
Authors: Yamada Kohdai , Shioya Ryouhei , Nishino Kohei , Furihata Hirotake , Hijikata Atsushi , Kaneko Mika K. , Kato Yukinari , Shirai Tsuyoshi , Kosako Hidetaka , Sawasaki Tatsuya 
Published: December 2023

AbstractReceptor proteins, such as epidermal growth factor receptor (EGFR), interact with other proteins in the extracellular region of the cell membrane to drive intracellular signalling. Therefore, analysis of extracellular protein-protein interactions (exPPIs) is important for understanding the biological function of receptor proteins. Here, we present an approach using a proximity biotinylation enzyme (AirID) fusion fragment of antigen binding (FabID) to analyse the proximity exPPIs of EGFR. AirID was C-terminally fused to the Fab fragment against EGFR (EGFR-FabID), which could then biotinylate the extracellular region of EGFR in several cell lines. Liquid Chromatography-Mass Spectrometry (LC-MS/MS) analysis indicated that many known EGFR interactors were identified as proximity exPPIs, along with many unknown candidate interactors, using EGFR-FabID. Interestingly, these proximity exPPIs were influenced by treatment with EGF ligand and its specific kinase inhibitor, gefitinib. These results indicate that FabID provides accurate proximity exPPI analysis of target receptor proteins on cell membranes with ligand and drug responses.
Remodeling of the ribosomal quality control and integrated stress response by viral ubiquitin deconjugases
Authors: Liu Jiangnan , Nagy Noemi , Ayala-Torres Carlos , Aguilar-Alonso Francisco , Morais-Esteves Francisco , Xu Shanshan , Masucci Maria G. 
Published: December 2023

AbstractThe strategies adopted by viruses to reprogram the translation and protein quality control machinery and promote infection are poorly understood. Here, we report that the viral ubiquitin deconjugase (vDUB)—encoded in the large tegument protein of Epstein-Barr virus (EBV BPLF1)—regulates the ribosomal quality control (RQC) and integrated stress responses (ISR). The vDUB participates in protein complexes that include the RQC ubiquitin ligases ZNF598 and LTN1. Upon ribosomal stalling, the vDUB counteracts the ubiquitination of the 40 S particle and inhibits the degradation of translation-stalled polypeptides by the proteasome. Impairment of the RQC correlates with the readthrough of stall-inducing mRNAs and with activation of a GCN2-dependent ISR that redirects translation towards upstream open reading frames (uORFs)- and internal ribosome entry sites (IRES)-containing transcripts. Physiological levels of active BPLF1 promote the translation of the EBV Nuclear Antigen (EBNA)1 mRNA in productively infected cells and enhance the release of progeny virus, pointing to a pivotal role of the vDUB in the translation reprogramming that enables efficient virus production.
Mechanically tunable organogels from highly charged polyoxometalate clusters loaded with fluorescent dyes
Authors: Zhang Fenghua , Li Zhong , Wang Xun 
Published: December 2023

AbstractInorganic nanowires-based organogel, a class of emerging organogel with convenient preparation, recyclability, and excellent mechanical properties, is in its infancy. Solidifying and functionalizing nanowires-based organogels by designing the gelator structure remains challenging. Here, we fabricate Ca2-P2W16 and Ca2-P2W15M nanowires utilizing highly charged [Ca2P2W16O60]10− and [Ca2P2W15MO60]14−/13− cluster units, respectively, which are then employed for preparing organogels. The mechanical performance and stability of prepared organogels are improved due to the enhanced interactions between nanowires and locked organic molecules. Compressive stress and tensile stress of Ca2-P2W16 nanowires-based organogel reach 34.5 and 29.0 kPa, respectively. The critical gel concentration of Ca2-P2W16 nanowires is as low as 0.28%. Single-molecule force spectroscopy confirms that the connections between cluster units and linkers can regulate the flexibility of nanowires. Furthermore, the incorporation of fluorophores into the organogels adds fluorescence properties. This work reveals the relationships between the microstructures of inorganic gelators and the properties of organogels, guiding the synthesis of high-performance and functional organogels.
Viruses under the Antarctic Ice Shelf are active and potentially involved in global nutrient cycles
Authors: Lopez-Simon Javier , Vila-Nistal Marina , Rosenova Aleksandra , De Corte Daniele , Baltar Federico , Martinez-Garcia Manuel 
Published: December 2023

AbstractViruses play an important role in the marine ecosystem. However, our comprehension of viruses inhabiting the dark ocean, and in particular, under the Antarctic Ice Shelves, remains limited. Here, we mine single-cell genomic, transcriptomic, and metagenomic data to uncover the viral diversity, biogeography, activity, and their role as metabolic facilitators of microbes beneath the Ross Ice Shelf. This is the largest Antarctic ice shelf with a major impact on global carbon cycle. The viral community found in the cavity under the ice shelf mainly comprises endemic viruses adapted to polar and mesopelagic environments. The low abundance of genes related to lysogenic lifestyle (<3%) does not support a predominance of the Piggyback-the-Winner hypothesis, consistent with a low-productivity habitat. Our results indicate a viral community actively infecting key ammonium and sulfur-oxidizing chemolithoautotrophs (e.g. Nitrosopumilus spp, Thioglobus spp.), supporting a “kill-the-winner” dynamic. Based on genome analysis, these viruses carry specific auxiliary metabolic genes potentially involved in nitrogen, sulfur, and phosphorus acquisition. Altogether, the viruses under Antarctic ice shelves are putatively involved in programming the metabolism of ecologically relevant microbes that maintain primary production in these chemosynthetically-driven ecosystems, which have a major role in global nutrient cycles.
Elucidating the structure-stability relationship of Cu single-atom catalysts using operando surface-enhanced infrared absorption spectroscopy
Authors: Zhang Li , Yang Xiaoju , Yuan Qing , Wei Zhiming , Ding Jie , Chu Tianshu , Rong Chao , Zhang Qiao , Ye Zhenkun , Xuan Fu-Zhen , Zhai Yueming , Zhang Bowei , Yang Xuan 
Published: December 2023

AbstractUnderstanding the structure-stability relationship of catalysts is imperative for the development of high-performance electrocatalytic devices. Herein, we utilize operando attenuated total reflectance surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS) to quantitatively monitor the evolution of Cu single-atom catalysts (SACs) during the electrochemical reduction of CO2 (CO2RR). Cu SACs are converted into 2-nm Cu nanoparticles through a reconstruction process during CO2RR. The evolution rate of Cu SACs is highly dependent on the substrates of the catalysts due to the coordination difference. Density functional theory calculations demonstrate that the stability of Cu SACs is highly dependent on their formation energy, which can be manipulated by controlling the affinity between Cu sites and substrates. This work highlights the use of operando ATR-SEIRAS to achieve mechanistic understanding of structure-stability relationship for long-term applications.
Mapping combinatorial drug effects to DNA damage response kinase inhibitors
Authors: Zhang Hanrui , Kreis Julian , Schelhorn Sven-Eric , Dahmen Heike , Grombacher Thomas , Zühlsdorf Michael , Zenke Frank T. , Guan Yuanfang 
Published: December 2023

AbstractOne fundamental principle that underlies various cancer treatments, such as traditional chemotherapy and radiotherapy, involves the induction of catastrophic DNA damage, leading to the apoptosis of cancer cells. In our study, we conduct a comprehensive dose-response combination screening focused on inhibitors that target key kinases involved in the DNA damage response (DDR): ATR, ATM, and DNA-PK. This screening involves 87 anti-cancer agents, including six DDR inhibitors, and encompasses 62 different cell lines spanning 12 types of tumors, resulting in a total of 17,912 combination treatment experiments. Within these combinations, we analyze the most effective and synergistic drug pairs across all tested cell lines, considering the variations among cancers originating from different tissues. Our analysis reveals inhibitors of five DDR-related pathways (DNA topoisomerase, PLK1 kinase, p53-inducible ribonucleotide reductase, PARP, and cell cycle checkpoint proteins) that exhibit strong combinatorial efficacy and synergy when used alongside ATM/ATR/DNA-PK inhibitors.
Sphingosine-1-phosphate suppresses GLUT activity through PP2A and counteracts hyperglycemia in diabetic red blood cells
Authors: Thomas Nadine , Schröder Nathalie H. , Nowak Melissa K. , Wollnitzke Philipp , Ghaderi Shahrooz , von Wnuck Lipinski Karin , Wille Annalena , Deister-Jonas Jennifer , Vogt Jens , Gräler Markus H. , Dannenberg Lisa , Buschmann Tobias , Westhoff Philipp , Polzin Amin , Kelm Malte , Keul Petra , Weske Sarah , Levkau Bodo 
Published: December 2023

AbstractRed blood cells (RBC) are the major carriers of sphingosine-1-phosphate (S1P) in blood. Here we show that variations in RBC S1P content achieved by altering S1P synthesis and transport by genetic and pharmacological means regulate glucose uptake and metabolic flux. This is due to S1P-mediated activation of the catalytic protein phosphatase 2 (PP2A) subunit leading to reduction of cell-surface glucose transporters (GLUTs). The mechanism dynamically responds to metabolic cues from the environment by increasing S1P synthesis, enhancing PP2A activity, reducing GLUT phosphorylation and localization, and diminishing glucose uptake in RBC from diabetic mice and humans. Functionally, it protects RBC against lipid peroxidation in hyperglycemia and diabetes by activating the pentose phosphate pathway. Proof of concept is provided by the resistance of mice lacking the S1P exporter MFSD2B to diabetes-induced HbA1c elevation and thiobarbituric acid reactive substances (TBARS) generation in diabetic RBC. This mechanism responds to pharmacological S1P analogues such as fingolimod and may be functional in other insulin-independent tissues making it a promising therapeutic target.
Visible light-induced switching of soft matter materials properties based on thioindigo photoswitches
Authors: Walden Sarah L. , Nguyen Phuong H. D. , Li Hao-Kai , Liu Xiaogang , Le Minh T. N. , Xian Jun Loh , Barner-Kowollik Christopher , Truong Vinh X. 
Published: December 2023

AbstractThioindigos are visible light responsive photoswitches with excellent spatial control over the conformational change between their trans- and cis- isomers. However, they possess limited solubility in all conventional organic solvents and polymers, hindering their application in soft matter materials. Herein, we introduce a strategy for the covalent insertion of thioindigo units into polymer main chains, enabling thioindigos to function within crosslinked polymeric hydrogels. We overcome their solubility issue by developing a thioindigo bismethacrylate linker able to undergo radical initiated thiol-ene reaction for step-growth polymerization, generating indigo-containing polymers. The optimal wavelength for the reversible trans-/cis- isomerisation of thioindigo was elucidated by constructing a detailed photochemical action plot of their switching efficiencies at a wide range of monochromatic wavelengths. Critically, indigo-containing polymers display significant photoswitching of the materials’ optical and physical properties in organic solvents and water. Furthermore, the photoswitching of thioindigo within crosslinked structures enables visible light induced modulation of the hydrogel stiffness. Both the thioindigo-containing hydrogels and photoswitching processes are non-toxic to cells, thus offering opportunities for advanced applications in soft matter materials and biology-related research.
Type I collagen and fibromodulin enhance the tenogenic phenotype of hASCs and their potential for tendon regeneration
Authors: Tu Tian , Shi Yuan , Zhou Boya , Wang Xiaoyu , Zhang Wenjie , Zhou Guangdong , Mo Xiumei , Wang Wenbo , Wu Jinglei , Liu Wei 
Published: December 2023

AbstractOur previous work demonstrated the tendon-derived extracellular matrix (ECM) extracts as vital niches to specifically direct mesenchymal stem cells towards tenogenic differentiation. This study aims to further define the effective ECM molecules capable of teno-lineage induction on human adipose-derived stem cells (hASCs) and test their function for tendon engineering. By detecting the teno-markers expression levels in hASCs exposed to various substrate coatings, collagen I (COL1) and fibromodulin (FMOD) were identified to be the key molecules as a combination and further employed to the modification of poly(L-lactide-co-ε-caprolactone) electrospun nanoyarns, which showed advantages in inducting seeded hASCs for teno-lineage specific differentiation. Under dynamic mechanical loading, modified scaffold seeded with hASCs formed neo-tendon in vitro at the histological level and formed better tendon tissue in vivo with mature histology and enhanced mechanical properties. Primary mechanistic investigation with RNA sequencing demonstrated that the inductive mechanism of these two molecules for hASCs tenogenic differentiation was directly correlated with positive regulation of peptidase activity, regulation of cell-substrate adhesion and regulation of cytoskeletal organization. These biological processes were potentially affected by LOC101929398/has-miR-197-3p/TENM4 ceRNA regulation axis. In summary, COL1 and FMOD in combination are the major bioactive molecules in tendon ECM for likely directing tenogenic phenotype of hASCs and certainly valuable for hASCs-based tendon engineering.
Does students’ awareness of school-track-related stereotypes exacerbate inequalities in education?
Authors: Bardach Lisa , Neuendorf Claudia , Murayama Kou , Fahrbach Thorsten , Knigge Michel , Nagengast Benjamin , Trautwein Ulrich 
Published: December 2023

AbstractEarly ability tracking increases inequalities in education. It has been proposed that the awareness of negative school-track-related stereotypes contributes to educational inequalities, as stereotype awareness interferes with students’ abilities to thrive, particularly those in lower, stigmatized tracks. The present study tested this assumption in a sample of 3880 German secondary school students from three tracks, who were assessed four times on stereotype awareness regarding their own school track and academic outcomes (achievement, engagement, self-concept) between Grades 5 and 8. Students in the lowest track reported higher levels of stereotype awareness than higher track students or students attending a combined track. Stereotype awareness increased across time in all tracks. Contrary to our preregistered hypotheses, however, the results from multigroup models revealed that (changes in) stereotype awareness were not more strongly related to (changes in) most outcomes in the lowest track in comparison with the other two tracks.