bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel endoplasmic stress mediator, Kelch domain containing 7B (KLHDC7B), increased Harakiri (HRK) in the SubAB-induced apoptosis signaling pathway
Authors: Yahiro Kinnosuke , Ogura Kohei , Tsutsuki Hiroyasu , Iyoda Sunao , Ohnishi Makoto , Moss Joel 
Published: November 2021

AbstractLocus for Enterocyte Effacement (LEE)-positive Shiga-toxigenicEscherichia coli(STEC) contributes to many global foodborne diseases, with infection characterized by severe gastrointestinal symptoms, including bloody diarrhea. The incidence of LEE-negative STEC-mediated disease is also increasing globally. Subtilase cytotoxin (SubAB) is released by some LEE-negative STEC strains. It cleaves BiP, which is a chaperone protein located in the endoplasmic reticulum (ER), thereby causing apoptosis induced by ER stress. To date, the apoptotic signaling pathway mediated by SubAB has not been identified. In the current study, RNA-seq analysis showed that SubAB significantly induced the expression of Kelch domain containing 7B (KLHDC7B). We explored the role of KLHDC7B in the SubAB-induced apoptotic pathway. SubAB-induced KLHDC7B mRNA expression was increased after 12 h of incubation of toxin with HeLa cells. KLHDC7B expression was downregulated by knockdown of PKR-like endoplasmic reticulum kinase (PERK), CEBP homologous protein (CHOP), activating transcription factor 4 (ATF4), and CEBP β (CEBPB). KLHDC7B knockdown suppressed SubAB-stimulated CHOP expression, poly(ADP-ribose) polymerase (PARP) cleavage, and cytotoxicity. The over-expressed KLHDC7B was localized to the nucleus and cytosolic fractions. Next, we used RNA-seq to analyze the effect of KLHDC7B knockdown on apoptosis induced by SubAB, and found that the gene encoding for the pro-apoptotic Bcl-2 family protein, Harakiri (HRK), was upregulated in SubAB-treated control cells. However, this effect was not observed in SubAB-treated KLHDC7B-knockdown cells. Therefore, we identified the pathway through which SubAB-induced KLHDC7B regulates HRK expression, which is essential for apoptosis in toxin-mediated ER stress.
Spatiotemporal regulation of endogenous MSCs using a functional injectable hydrogel system for cartilage regeneration
Authors: Dong Yunsheng , Liu Yufei , Chen Yuehua , Sun Xun , Zhang Lin , Zhang Zhiling , Wang Yanying , Qi Chunxiao , Wang Shufang , Yang Qiang 
Published: November 2021

AbstractHydrogels have been extensively favored as drug and cell carriers for the repair of knee cartilage defects. Recruiting mesenchymal stem cells (MSCs) in situ to the defect region could reduce the risk of contamination during cell delivery, which is a highly promising strategy to enhance cartilage repair. Here, a cell-free cartilage tissue engineering (TE) system was developed by applying an injectable chitosan/silk fibroin hydrogel. The hydrogel system could release first stromal cell-derived factor-1 (SDF-1) and then kartogenin (KGN) in a unique sequential drug release mode, which could spatiotemporally promote the recruitment and chondrogenic differentiation of MSCs. This system showed good performance when formulated with SDF-1 (200 ng/mL) and PLGA microspheres loaded with KGN (10 μΜ). The results showed that the hydrogel had good injectability and a reticular porous structure. The microspheres were distributed uniformly in the hydrogel and permitted the sequential release of SDF-1 and KGN. The results of in vitro experiments showed that the hydrogel system had good cytocompatibility and promoted the migration and differentiation of MSCs into chondrocytes. In vivo experiments on articular cartilage defects in rabbits showed that the cell-free hydrogel system was beneficial for cartilage regeneration. Therefore, the composite hydrogel system shows potential for application in cell-free cartilage TE.
Three-dimensional printing of bioceramic-induced macrophage exosomes: immunomodulation and osteogenesis/angiogenesis
Authors: Sun Yuhua , Zhang Bingjun , Zhai Dong , Wu Chengtie 
Published: November 2021

AbstractExosomes have attracted increasing attention in tissue regeneration and repair due to their roles in intercellular communication. Developing a customized delivery system is key to exosome-based regenerative therapeutics. Bioceramics play an important role in the immunomodulation of macrophages. Here, three-dimensional (3D) printing was applied to construct porous scaffolds with β-tricalcium phosphate (β-TCP) bioceramic-induced macrophage exosomes (BC-Exos). The three-dimensional-printed BC-Exo scaffolds, exhibiting a predefined structure and persistent release of exosomes, displayed distinct immunomodulatory effects and improved osteogenesis/angiogenesis. The BC-Exos in the printed scaffolds modulated macrophage polarization and the expression of chemokines for the recruitment of bone marrow mesenchymal stem cells (BMSCs) and endothelial cells. Scaffolds with BC-Exos from macrophages with a mixed phenotype significantly enhanced the osteogenic differentiation and immunosuppression of BMSCs and improved the angiogenic activity of human umbilical vein endothelial cells in vitro. For the potential mechanism, β-TCP bioceramics have an important effect on the immunomodulation of macrophages by regulating gene expression, increasing exosome production, and altering exosomal miRNA cargos, thereby affecting the paracrine effects of BC-Exos on immunomodulation and osteogenesis/angiogenesis. This study suggests that 3D printing of bioceramic-induced macrophage exosomes may be a useful strategy for tissue engineering and regenerative medicine.
Large scale discovery of coronavirus-host factor protein interaction motifs reveals SARS-CoV-2 specific mechanisms and vulnerabilities
Authors: Kruse Thomas , Benz Caroline , Garvanska Dimitriya H. , Lindqvist Richard , Mihalic Filip , Coscia Fabian , Inturi Raviteja , Sayadi Ahmed , Simonetti Leandro , Nilsson Emma , Ali Muhammad , Kliche Johanna , Moliner Morro Ainhoa , Mund Andreas , Andersson Eva , McInerney Gerald , Mann Matthias , Jemth Per , Davey Norman E. , Överby Anna K. , Nilsson Jakob , Ivarsson Ylva 
Published: November 2021

AbstractViral proteins make extensive use of short peptide interaction motifs to hijack cellular host factors. However, most current large-scale methods do not identify this important class of protein-protein interactions. Uncovering peptide mediated interactions provides both a molecular understanding of viral interactions with their host and the foundation for developing novel antiviral reagents. Here we describe a viral peptide discovery approach covering 23 coronavirus strains that provides high resolution information on direct virus-host interactions. We identify 269 peptide-based interactions for 18 coronaviruses including a specific interaction between the human G3BP1/2 proteins and an ΦxFG peptide motif in the SARS-CoV-2 nucleocapsid (N) protein. This interaction supports viral replication and through its ΦxFG motif N rewires the G3BP1/2 interactome to disrupt stress granules. A peptide-based inhibitor disrupting the G3BP1/2-N interaction dampened SARS-CoV-2 infection showing that our results can be directly translated into novel specific antiviral reagents.
Resurgent Na+ currents promote ultrafast spiking in projection neurons that drive fine motor control
Authors: Zemel Benjamin M. , Nevue Alexander A. , Dagostin Andre , Lovell Peter V. , Mello Claudio V. , von Gersdorff Henrique 
Published: November 2021

AbstractThe underlying mechanisms that promote precise spiking in upper motor neurons controlling fine motor skills are not well understood. Here we report that projection neurons in the adult zebra finch song nucleus RA display robust high-frequency firing, ultra-narrow spike waveforms, superfast Na+ current inactivation kinetics, and large resurgent Na+ currents (INaR). These properties of songbird pallial motor neurons closely resemble those of specialized large pyramidal neurons in mammalian primary motor cortex. They emerge during the early phases of song development in males, but not females, coinciding with a complete switch of Na+ channel subunit expression from Navβ3 to Navβ4. Dynamic clamping and dialysis of Navβ4’s C-terminal peptide into juvenile RA neurons provide evidence that Navβ4, and its associated INaR, promote neuronal excitability. We thus propose that INaR modulates the excitability of upper motor neurons that are required for the execution of fine motor skills.
Cooperative herbivory between two important pests of rice
Authors: Liu Qingsong , Hu Xiaoyun , Su Shuangli , Ning Yuese , Peng Yufa , Ye Gongyin , Lou Yonggen , Turlings Ted C. J. , Li Yunhe 
Published: November 2021

AbstractNormally, when different species of herbivorous arthropods feed on the same plant this leads to fitness-reducing competition. We found this to be different for two of Asia’s most destructive rice pests, the brown planthopper and the rice striped stem borer. Both insects directly and indirectly benefit from jointly attacking the same host plant. Double infestation improved host plant quality, particularly for the stemborer because the planthopper fully suppresses caterpillar-induced production of proteinase inhibitors. It also reduced the risk of egg parasitism, due to diminished parasitoid attraction. Females of both pests have adapted their oviposition behaviour accordingly. Their strong preference for plants infested by the other species even overrides their avoidance of plants already attacked by conspecifics. This cooperation between herbivores is telling of adaptations resulting from the evolution of plant-insect interactions, and points out mechanistic vulnerabilities that can be targeted to control these major pests.
Electrochemical C–N bond activation for deaminative reductive coupling of Katritzky salts
Authors: Liu Yeqing , Tao Xiangzhang , Mao Yu , Yuan Xin , Qiu Jiangkai , Kong Linyu , Ni Shengyang , Guo Kai , Wang Yi , Pan Yi 
Published: November 2021

AbstractElectrosynthesis has received great attention among researchers in both academia and industry as an ideal technique to promote single electron reduction without the use of expensive catalysts. In this work, we report the electrochemical reduction of Katritzky salts to alkyl radicals by sacrificing the easily accessible metal anode. This catalyst and electrolyte free platform has broad applicability to single electron transfer chemistry, including fluoroalkenylation, alkynylation and thiolation. The deaminative functionalization is facilitated by the rapid molecular diffusion across microfluidic channels, demonstrating the practicality that outpaces the conventional electrochemistry setups.
Water cluster in hydrophobic crystalline porous covalent organic frameworks
Authors: Tan Ke Tian , Tao Shanshan , Huang Ning , Jiang Donglin 
Published: November 2021

AbstractProgress over the past decades in water confinement has generated a variety of polymers and porous materials. However, most studies are based on a preconception that small hydrophobic pores eventually repulse water molecules, which precludes the exploration of hydrophobic microporous materials for water confinement. Here, we demonstrate water confinement across hydrophobic microporous channels in crystalline covalent organic frameworks. The frameworks are designed to constitute dense, aligned and one-dimensional polygonal channels that are open and accessible to water molecules. The hydrophobic microporous frameworks achieve full occupation of pores by water via synergistic nucleation and capillary condensation and deliver quick water exchange at low pressures. Water confinement experiments with large-pore frameworks pinpoint thresholds of pore size where confinement becomes dominated by high uptake pressure and large exchange hysteresis. Our results reveal a platform based on microporous hydrophobic covalent organic frameworks for water confinement.
Excitonic effects in absorption spectra of carbon dioxide reduction photocatalysts
Authors: Biswas Tathagata , Singh Arunima K. 
Published: November 2021

AbstractThe formation and disassociation of excitons play a crucial role in any photovoltaic or photocatalytic application. However, excitonic effects are seldom considered in materials discovery studies due to the monumental computational cost associated with the examination of these properties. Here, we study the excitonic properties of nearly 50 photocatalysts using state-of-the-art Bethe–Salpeter formalism. These ~50 materials were recently recognized as promising photocatalysts for CO2 reduction through a data-driven screening of 68,860 materials. Here, we propose three screening criteria based on the optical properties of these materials, taking excitonic effects into account, to further down select six materials. Furthermore, we study the correlation between the exciton binding energies obtained from the Bethe–Salpeter formalism and those obtained from the computationally much less-expensive Wannier–Mott model for these chemically diverse ~50 materials. This work presents a paradigm towards the inclusion of excitonic effects in future materials discovery for solar-energy harvesting applications.
Spin liquid and ferroelectricity close to a quantum critical point in PbCuTe2O6
Authors: Thurn Christian , Eibisch Paul , Ata Arif , Winkler Maximilian , Lunkenheimer Peter , Kézsmárki István , Tutsch Ulrich , Saito Yohei , Hartmann Steffi , Zimmermann Jan , Hanna Abanoub R. N. , Islam A. T. M. Nazmul , Chillal Shravani , Lake Bella , Wolf Bernd , Lang Michael 
Published: November 2021

AbstractGeometrical frustration among interacting spins combined with strong quantum fluctuations destabilize long-range magnetic order in favor of more exotic states such as spin liquids. By following this guiding principle, a number of spin liquid candidate systems were identified in quasi-two-dimensional (quasi-2D) systems. For 3D, however, the situation is less favorable as quantum fluctuations are reduced and competing states become more relevant. Here we report a comprehensive study of thermodynamic, magnetic and dielectric properties on single crystalline and pressed-powder samples of PbCuTe2O6, a candidate material for a 3D frustrated quantum spin liquid featuring a hyperkagome lattice. Whereas the low-temperature properties of the powder samples are consistent with the recently proposed quantum spin liquid state, an even more exotic behavior is revealed for the single crystals. These crystals show ferroelectric order at TFE ≈ 1 K, accompanied by strong lattice distortions, and a modified magnetic response—still consistent with a quantum spin liquid—but with clear indications for quantum critical behavior.
Chondrogenic differentiation induced by extracellular vesicles bound to a nanofibrous substrate
Authors: Casanova Marta R. , Osório Hugo , Reis Rui L. , Martins Albino , Neves Nuno M. 
Published: November 2021

AbstractExtracellular vesicles (EVs) are being increasingly studied owing to its regenerative potential, namely EVs derived from human bone marrow mesenchymal stem cells (hBM-MSCs). Those can be used for controlling inflammation, repairing injury, and enhancing tissue regeneration. Differently, the potential of EVs derived from human articular chondrocytes (hACs) to promote cartilage regeneration has not been thoroughly investigated. This work aims to develop an EVs immobilization system capable of selectively bind EVs present in conditioned medium obtained from cultures of hACs or hBM-MSC. For that, an anti-CD63 antibody was immobilized at the surface of an activated and functionalized electrospun nanofibrous mesh. The chondrogenic potential of bound EVs was further assessed by culturing hBM-MSCs during 28 days under basal conditions. EVs derived from hACs cultured under differentiation medium or from chondrogenically committed hBM-MSCs induced a chondrogenic phenotype characterized by marked induction of SOX9, COMP, Aggrecan and Collagen type II, and matrix glycosaminoglycans synthesis. Indeed, both EVs immobilization systems outperformed the currently used chondroinductive strategies. These data show that naturally secreted EVs can guide the chondrogenic commitment of hBM-MSCs in the absence of any other chemical or genetic chondrogenic inductors based in medium supplementation.
Branch water uptake and redistribution in two conifers at the alpine treeline
Authors: Losso Adriano , Bär Andreas , Unterholzner Lucrezia , Bahn Michael , Mayr Stefan 
Published: November 2021

AbstractDuring winter, conifers at the alpine treeline suffer dramatic losses of hydraulic conductivity, which are successfully recovered during late winter. Previous studies indicated branch water uptake to support hydraulic recovery. We analyzed water absorption and redistribution inPicea abiesandLarix deciduagrowing at the treeline by in situ exposure of branches to δ2H-labelled water. Both species suffered high winter embolism rates (> 40–60% loss of conductivity) and recovered in late winter (< 20%). Isotopic analysis showed water to be absorbed over branches and redistributed within the crown during late winter. Labelled water was redistributed over 425 ± 5 cm within the axes system and shifted to the trunk, lower and higher branches (tree height 330 ± 40 cm). This demonstrated relevant branch water uptake and re-distribution in treeline conifers. The extent of water absorption and re-distribution was species-specific, withL. deciduashowing higher rates.In natura, melting snow might be the prime source for absorbed and redistributed water, enabling embolism repair and restoration of water reservoirs prior to the vegetation period. Pronounced water uptake in the deciduousL. deciduaindicated bark to participate in the process of water absorption.
Two-stage algorithms for visually exploring spatio-temporal clustering of avian influenza virus outbreaks in poultry farms
Authors: Wu Hong-Dar Isaac , Chao Day-Yu 
Published: November 2021

AbstractThe development of visual tools for the timely identification of spatio-temporal clusters will assist in implementing control measures to prevent further damage. From January 2015 to June 2020, a total number of 1463 avian influenza outbreak farms were detected in Taiwan and further confirmed to be affected by highly pathogenic avian influenza subtype H5Nx. In this study, we adopted two common concepts of spatio-temporal clustering methods, the Knox test and scan statistics, with visual tools to explore the dynamic changes of clustering patterns. Since most (68.6%) of the outbreak farms were detected in 2015, only the data from 2015 was used in this study. The first two-stage algorithm performs the Knox test, which established a threshold of 7 days and identified 11 major clusters in the six counties of southwestern Taiwan, followed by the standard deviational ellipse (SDE) method implemented on each cluster to reveal the transmission direction. The second algorithm applies scan likelihood ratio statistics followed by AGC index to visualize the dynamic changes of the local aggregation pattern of disease clusters at the regional level. Compared to the one-stage aggregation approach, Knox-based and AGC mapping were more sensitive in small-scale spatio-temporal clustering.
Capturing hidden regulation based on noise change of gene expression level from single cell RNA-seq in yeast
Authors: Itoh Thoma , Makino Takashi 
Published: November 2021

AbstractRecent progress in high throughput single cell RNA-seq (scRNA-seq) has activated the development of data-driven inferring methods of gene regulatory networks. Most network estimations assume that perturbations produce downstream effects. However, the effects of gene perturbations are sometimes compensated by a gene with redundant functionality (functional compensation). In order to avoid functional compensation, previous studies constructed double gene deletions, but its vast nature of gene combinations was not suitable for comprehensive network estimation. We hypothesized that functional compensation may emerge as a noise change without mean change (noise-only change) due to varying physical properties and strong compensation effects. Here, we show compensated interactions, which are not detected by mean change, are captured by noise-only change quantified from scRNA-seq. We investigated whether noise-only change genes caused by a single deletion of STP1 and STP2, which have strong functional compensation, are enriched in redundantly regulated genes. As a result, noise-only change genes are enriched in their redundantly regulated genes. Furthermore, novel downstream genes detected from noise change are enriched in “transport”, which is related to known downstream genes. Herein, we suggest the noise difference comparison has the potential to be applied as a new strategy for network estimation that capture even compensated interaction.
Association of pre-ESRD care education with patient outcomes in a 10-year longitudinal study of patients with CKD stages 3–5 in Taiwan
Authors: Chou Chu-Lin , Chung Chi-Hsiang , Chiu Hui-Wen , Liao Chia-Te , Wu Chia-Chao , Hsu Yung-Ho , Chien Wu-Chien 
Published: November 2021

AbstractThere is little comprehensive education for people with end-stage renal disease (ESRD) progress. We investigated the differences in terms of outcomes between patients with CKD stages 3–5 who enrolled and did not enroll in the pre-ESRD care education in Taiwan. This retrospective cohort study was conducted using data from the National Health Insurance Research Database (NHIRD). All patients diagnosed with CKD stages 3–5 who received the pre-ESRD care education through the pay for performance (P4P) program were enrolled. Based on whether or not they participated in the program, they were categorized into P4P or non-P4P groups. All analyses were performed from January 2006 through December 2015. Study outcomes were risk of hemodialysis dependency, hospitalization, and all-cause mortality. In this study of 29,337 patients, those with CKD stages 3–5 in the P4P group had lower events of hemodialysis, hospitalization, and all-cause mortality compared to patients in the non-P4P group. This study suggested that pre-ESRD care education is associated with increased patient outcomes, resulting in lower hemodialysis and hospitalization events and a higher overall survival rate in patients with CKD stages 3–5. Patient education could raise opportunities to improve pre-ESRD care by reaching patients outside the traditional health care setting.
β-elimination of hyaluronate by red king crab hyaluronidase
Authors: Sliadovskii Dmitrii , Ponomareva Tatyana , Molchanov Maxim , Pozdnyakova-Filatova Irina , Timchenko Maria , Marchenkov Victor , Gusev Oleg , Sogorin Evgeny 
Published: November 2021

AbstractCrustacean hyaluronidases are poorly understood both in terms of their enzymatic properties and in terms of their structural features. In this work, we show that the hepatopancreas homogenate of the red king crab has a hyaluronidase activity that is an order of magnitude higher than its commercial counterpart. Zymography revealed that the molecular weight of a protein with hyalorunidase activity is 40–50 kDa. Analysis of the hepatopancreas transcriptome and results of cloning and sequencing of cDNA revealed a hyaluronidase sequence with an expected molecular weight of 42.5 kDa. Further analysis showed that hyaluronat enzymatic cleavage follows the$$\beta $$β-elimination mechanism, which is well known for bacterial hyaluronidases. The results of ion-exchange chromatography showed that the final product of hyaluronate degradation is unsaturated tetrasaccharide. Thus, we identified a new hyaluronidase of higher eukaryotes, which is not integrated into the modern classification of hyaluronidases.