bluuebunny/crossref_metadata_2025_split huggingface dataset:
PBK drives PARP inhibitor resistance through the TRIM37/NFκB axis in ovarian cancer
Authors: Ma Hanlin , Qi Gonghua , Han Fang , Peng Jiali , Yuan Cunzhong , Kong Beihua 
Published: July 2022

AbstractResistance to PARP inhibitors (PARPi) remains a therapeutic challenge in ovarian cancer patients. PDZ-binding kinase (PBK) participates in the chemoresistance of many malignancies. However, the role of PBK in PARPi resistance of ovarian cancer is obscure. In the current study, we demonstrated that overexpression of PBK contributed to olaparib resistance in ovarian cancer cells. Knockdown of PBK sensitized olaparib-resistant SKOV3 cells to olaparib. Inhibition of PBK using a specific inhibitor enhanced the therapeutic efficiency of olaparib. Mechanically, PBK directly interacted with TRIM37 to promote its phosphorylation and nuclear translocation. which subsequently activates the NFκB pathway. Additionally, PBK enhanced olaparib resistance of ovarian cancer by regulating the NFκB/TRIM37 axis in vitro and in vivo. In conclusion, PBK confers ovarian cancer resistance to PARPi through activating the TRIM37-mediated NFκB pathway, and targeted inhibition of PBK provided the new therapy to improve PARPi treatment outcomes for ovarian cancer patients.
Bone morphogenetic protein 7 mediates stem cells migration and angiogenesis: therapeutic potential for endogenous pulp regeneration
Authors: Liang Cheng , Liang Qingqing , Xu Xun , Liu Xiaojing , Gao Xin , Li Maojiao , Yang Jian , Xing Xiaotao , Huang Haisen , Tang Qi , Liao Li , Tian Weidong 
Published: July 2022

AbstractPulp loss is accompanied by the functional impairment of defense, sensory, and nutrition supply. The approach based on endogenous stem cells is a potential strategy for pulp regeneration. However, endogenous stem cell sources, exogenous regenerative signals, and neovascularization are major difficulties for pulp regeneration based on endogenous stem cells. Therefore, the purpose of our research is to seek an effective cytokines delivery strategy and bioactive materials to reestablish an ideal regenerative microenvironment for pulp regeneration. In in vitro study, we investigated the effects of Wnt3a, transforming growth factor-beta 1, and bone morphogenetic protein 7 (BMP7) on human dental pulp stem cells (h-DPSCs) and human umbilical vein endothelial cells. 2D and 3D culture systems based on collagen gel, matrigel, and gelatin methacryloyl were fabricated to evaluate the morphology and viability of h-DPSCs. In in vivo study, an ectopic nude mouse model and an in situ beagle dog model were established to investigate the possibility of pulp regeneration by implanting collagen gel loading BMP7. We concluded that BMP7 promoted the migration and odontogenic differentiation of h-DPSCs and vessel formation. Collagen gel maintained the cell adhesion, cell spreading, and cell viability of h-DPSCs in 2D or 3D culture. The transplantation of collagen gel loading BMP7 induced vascularized pulp-like tissue regeneration in vivo. The injectable approach based on collagen gel loading BMP7 might exert promising therapeutic application in endogenous pulp regeneration.
Influencing cognitive performance via social interactions: a novel therapeutic approach for brain disorders based on neuroanatomical mapping?
Authors: Lanooij Suzanne D. , Eisel Ulrich L. M. , Drinkenburg Wilhelmus H. I. M. , van der Zee Eddy A. , Kas Martien J. H. 
Published: July 2022

AbstractMany psychiatric and neurological disorders present deficits in both the social and cognitive domain. In this perspectives article, we provide an overview and the potential of the existence of an extensive neurobiological substrate underlying the close relationship between these two domains. By mapping the rodent brain regions involved in the social and/or cognitive domain, we show that the vast majority of brain regions involved in the cognitive domain are also involved in the social domain. The identified neuroanatomical overlap has an evolutionary basis, as complex social behavior requires cognitive skills, and aligns with the reported functional interactions of processes underlying cognitive and social performance. Based on the neuroanatomical mapping, recent (pre-)clinical findings, and the evolutionary perspective, we emphasize that the social domain requires more focus as an important treatment target and/or biomarker, especially considering the presently limited treatment strategies for these disorders.
Energy-efficient pathway for selectively exciting solute molecules to high vibrational states via solvent vibration-polariton pumping
Authors: Li Tao E. , Nitzan Abraham , Subotnik Joseph E. 
Published: July 2022

AbstractSelectively exciting target molecules to high vibrational states is inefficient in the liquid phase, which restricts the use of IR pumping to catalyze ground-state chemical reactions. Here, we demonstrate that this inefficiency can sometimes be solved by confining the liquid to an optical cavity under vibrational strong coupling conditions. For a liquid solution of 13CO2 solute in a 12CO2 solvent, cavity molecular dynamics simulations show that exciting a polariton (hybrid light-matter state) of the solvent with an intense laser pulse, under suitable resonant conditions, may lead to a very strong (>3 quanta) and ultrafast (<1 ps) excitation of the solute, even though the solvent ends up being barely excited. By contrast, outside a cavity the same input pulse fluence can excite the solute by only half a vibrational quantum and the selectivity of excitation is low. Our finding is robust under different cavity volumes, which may lead to observable cavity enhancement on IR photochemical reactions in Fabry–Pérot cavities.
A Bayesian approach to infer recombination patterns in coronaviruses
Authors: Müller Nicola F. , Kistler Kathryn E. , Bedford Trevor 
Published: July 2022

AbstractAs shown during the SARS-CoV-2 pandemic, phylogenetic and phylodynamic methods are essential tools to study the spread and evolution of pathogens. One of the central assumptions of these methods is that the shared history of pathogens isolated from different hosts can be described by a branching phylogenetic tree. Recombination breaks this assumption. This makes it problematic to apply phylogenetic methods to study recombining pathogens, including, for example, coronaviruses. Here, we introduce a Markov chain Monte Carlo approach that allows inference of recombination networks from genetic sequence data under a template switching model of recombination. Using this method, we first show that recombination is extremely common in the evolutionary history of SARS-like coronaviruses. We then show how recombination rates across the genome of the human seasonal coronaviruses 229E, OC43 and NL63 vary with rates of adaptation. This suggests that recombination could be beneficial to fitness of human seasonal coronaviruses. Additionally, this work sets the stage for Bayesian phylogenetic tracking of the spread and evolution of SARS-CoV-2 in the future, even as recombinant viruses become prevalent.
Thalamo-hippocampal pathway regulates incidental memory capacity in mice
Authors: Torromino G. , Loffredo V. , Cavezza D. , Sonsini G. , Esposito F. , Crevenna A. H. , Gioffrè M. , De Risi M. , Treves A. , Griguoli M. , De Leonibus E. 
Published: July 2022

AbstractIncidental memory can be challenged by increasing either the retention delay or the memory load. The dorsal hippocampus (dHP) appears to help with both consolidation from short-term (STM) to long-term memory (LTM), and higher memory loads, but the mechanism is not fully understood. Here we find that female mice, despite having the same STM capacity of 6 objects and higher resistance to distraction in our different object recognition task (DOT), when tested over 1 h or 24 h delays appear to transfer to LTM only 4 objects, whereas male mice have an STM capacity of 6 objects in this task. In male mice the dHP shows greater activation (as measured by c-Fos expression), whereas female mice show greater activation of the ventral midline thalamus (VMT). Optogenetic inhibition of the VMT-dHP pathway during off-line memory consolidation enables 6-object LTM retention in females, while chemogenetic VMT-activation impairs it in males. Thus, removing or enhancing sub-cortical inhibitory control over the hippocampus leads to differences in incidental memory.
An epigenome atlas of neural progenitors within the embryonic mouse forebrain
Authors: Rhodes Christopher T. , Thompson Joyce J. , Mitra Apratim , Asokumar Dhanya , Lee Dongjin R. , Lee Daniel J. , Zhang Yajun , Jason Eva , Dale Ryan K. , Rocha Pedro P. , Petros Timothy J. 
Published: July 2022

AbstractA comprehensive characterization of epigenomic organization in the embryonic mouse forebrain will enhance our understanding of neurodevelopment and provide insight into mechanisms of neurological disease. Here we collected single-cell chromatin accessibility profiles from four distinct neurogenic regions of the embryonic mouse forebrain using single nuclei ATAC-Seq (snATAC-Seq). We identified thousands of differentially accessible peaks, many restricted to distinct progenitor cell types or brain regions. We integrated snATAC-Seq and single cell transcriptome data to characterize changes of chromatin accessibility at enhancers and promoters with associated transcript abundance. Multi-modal integration of histone modifications (CUT&Tag and CUT&RUN), promoter-enhancer interactions (Capture-C) and high-order chromatin structure (Hi-C) extended these initial observations. This dataset reveals a diverse chromatin landscape with region-specific regulatory mechanisms and genomic interactions in distinct neurogenic regions of the embryonic mouse brain and represents an extensive public resource of a ‘ground truth’ epigenomic landscape at this critical stage of neurogenesis.
Kinesin-8-specific loop-2 controls the dual activities of the motor domain according to tubulin protofilament shape
Authors: Hunter Byron , Benoit Matthieu P. M. H. , Asenjo Ana B. , Doubleday Caitlin , Trofimova Daria , Frazer Corey , Shoukat Irsa , Sosa Hernando , Allingham John S. 
Published: July 2022

AbstractKinesin-8s are dual-activity motor proteins that can move processively on microtubules and depolymerize microtubule plus-ends, but their mechanism of combining these distinct activities remains unclear. We addressed this by obtaining cryo-EM structures (2.6–3.9 Å) ofCandida albicansKip3 in different catalytic states on the microtubule lattice and on a curved microtubule end mimic. We also determined a crystal structure of microtubule-unboundCaKip3-ADP (2.0 Å) and analyzed the biochemical activity ofCaKip3 and kinesin-1 mutants. These data reveal that the microtubule depolymerization activity of kinesin-8 originates from conformational changes of its motor core that are amplified by dynamic contacts between its extended loop-2 and tubulin. On curved microtubule ends, loop-1 inserts into preceding motor domains, forming head-to-tail arrays of kinesin-8s that complement loop-2 contacts with curved tubulin and assist depolymerization. On straight tubulin protofilaments in the microtubule lattice, loop-2-tubulin contacts inhibit conformational changes in the motor core, but in the ADP-Pi state these contacts are relaxed, allowing neck-linker docking for motility. We propose that these tubulin shape-induced alternations between pro-microtubule-depolymerization and pro-motility kinesin states, regulated by loop-2, are the key to the dual activity of kinesin-8 motors.
Mechanism of threonine ADP-ribosylation of F-actin by a Tc toxin
Authors: Belyy Alexander , Lindemann Florian , Roderer Daniel , Funk Johanna , Bardiaux Benjamin , Protze Jonas , Bieling Peter , Oschkinat Hartmut , Raunser Stefan 
Published: July 2022

AbstractTc toxins deliver toxic enzymes into host cells by a unique injection mechanism. One of these enzymes is the actin ADP-ribosyltransferase TccC3, whose activity leads to the clustering of the cellular cytoskeleton and ultimately cell death. Here, we show in atomic detail how TccC3 modifies actin. We find that the ADP-ribosyltransferase does not bind to G-actin but interacts with two consecutive actin subunits of F-actin. The binding of TccC3 to F-actin occurs via an induced-fit mechanism that facilitates access of NAD+ to the nucleotide binding pocket. The following nucleophilic substitution reaction results in the transfer of ADP-ribose to threonine-148 of F-actin. We demonstrate that this site-specific modification of F-actin prevents its interaction with depolymerization factors, such as cofilin, which impairs actin network turnover and leads to steady actin polymerization. Our findings reveal in atomic detail a mechanism of action of a bacterial toxin through specific targeting and modification of F-actin.
Polycomb-lamina antagonism partitions heterochromatin at the nuclear periphery
Authors: Siegenfeld Allison P. , Roseman Shelby A. , Roh Heejin , Lue Nicholas Z. , Wagen Corin C. , Zhou Eric , Johnstone Sarah E. , Aryee Martin J. , Liau Brian B. 
Published: July 2022

AbstractThe genome can be divided into two spatially segregated compartments, A and B, which partition active and inactive chromatin states. While constitutive heterochromatin is predominantly located within the B compartment near the nuclear lamina, facultative heterochromatin marked by H3K27me3 spans both compartments. How epigenetic modifications, compartmentalization, and lamina association collectively maintain heterochromatin architecture remains unclear. Here we develop Lamina-Inducible Methylation and Hi-C (LIMe-Hi-C) to jointly measure chromosome conformation, DNA methylation, and lamina positioning. Through LIMe-Hi-C, we identify topologically distinct sub-compartments with high levels of H3K27me3 and differing degrees of lamina association. Inhibition of Polycomb repressive complex 2 (PRC2) reveals that H3K27me3 is essential for sub-compartment segregation. Unexpectedly, PRC2 inhibition promotes lamina association and constitutive heterochromatin spreading into H3K27me3-marked B sub-compartment regions. Consistent with this repositioning, genes originally marked with H3K27me3 in the B compartment, but not the A compartment, remain largely repressed, suggesting that constitutive heterochromatin spreading can compensate for H3K27me3 loss at a transcriptional level. These findings demonstrate that Polycomb sub-compartments and their antagonism with lamina association are fundamental features of genome structure. More broadly, by jointly measuring nuclear position and Hi-C contacts, our study demonstrates how compartmentalization and lamina association represent distinct but interdependent modes of heterochromatin regulation.
In-plane strain engineering in ultrathin noble metal nanosheets boosts the intrinsic electrocatalytic hydrogen evolution activity
Authors: Wu Geng , Han Xiao , Cai Jinyan , Yin Peiqun , Cui Peixin , Zheng Xusheng , Li Hai , Chen Cai , Wang Gongming , Hong Xun 
Published: July 2022

AbstractStrain has been shown to modulate the electronic structure of noble metal nanomaterials and alter their catalytic performances. Since strain is spatially dependent, it is challenging to expose the active strained interfaces by structural engineering with atomic precision. Herein, we report a facile method to manipulate the planar strain in ultrathin noble metal nanosheets by constructing amorphous–crystalline phase boundaries that can expose the active strained interfaces. Geometric-phase analysis and electron diffraction profile demonstrate the in-plane amorphous–crystalline boundaries can induce about 4% surface tensile strain in the nanosheets. The strained Ir nanosheets display substantially enhanced intrinsic activity toward the hydrogen evolution reaction electrocatalysis with a turnover frequency value 4.5-fold higher than the benchmark Pt/C catalyst. Density functional theory calculations verify that the tensile strain optimizes the d-band states and hydrogen adsorption properties of the strained Ir nanosheets to improve catalysis. Furthermore, the in-plane strain engineering method is demonstrated to be a general approach to boost the hydrogen evolution performance of Ru and Rh nanosheets.
A DNA origami rotary ratchet motor
Authors: Pumm Anna-Katharina , Engelen Wouter , Kopperger Enzo , Isensee Jonas , Vogt Matthias , Kozina Viktorija , Kube Massimo , Honemann Maximilian N. , Bertosin Eva , Langecker Martin , Golestanian Ramin , Simmel Friedrich C. , Dietz Hendrik 
Published: July 2022

AbstractTo impart directionality to the motions of a molecular mechanism, one must overcome the random thermal forces that are ubiquitous on such small scales and in liquid solution at ambient temperature. In equilibrium without energy supply, directional motion cannot be sustained without violating the laws of thermodynamics. Under conditions away from thermodynamic equilibrium, directional motion may be achieved within the framework of Brownian ratchets, which are diffusive mechanisms that have broken inversion symmetry1–5. Ratcheting is thought to underpin the function of many natural biological motors, such as the F1F0-ATPase6–8, and it has been demonstrated experimentally in synthetic microscale systems (for example, to our knowledge, first in ref. 3) and also in artificial molecular motors created by organic chemical synthesis9–12. DNA nanotechnology13 has yielded a variety of nanoscale mechanisms, including pivots, hinges, crank sliders and rotary systems14–17, which can adopt different configurations, for example, triggered by strand-displacement reactions18,19 or by changing environmental parameters such as pH, ionic strength, temperature, external fields and by coupling their motions to those of natural motor proteins20–26. This previous work and considering low-Reynolds-number dynamics and inherent stochasticity27,28 led us to develop a nanoscale rotary motor built from DNA origami that is driven by ratcheting and whose mechanical capabilities approach those of biological motors such as F1F0-ATPase.
A consistent and corrected nighttime light dataset (CCNL 1992–2013) from DMSP-OLS data
Authors: Zhao Chenchen , Cao Xin , Chen Xuehong , Cui Xihong 
Published: July 2022

AbstractRemote sensing of nighttime light can observe the artificial lights at night on the planet’s surface. The Defense Meteorological Satellite Program’s Operational Line Scan (DMSP-OLS) data (1992–2013) provide planet-scale nighttime light data over a long-time span and have been widely used in areas such as urbanization monitoring, socio-economic parameters estimation, and disaster assessment. However, due to the lack of an on-board calibration system, sensor design defects, limited light detection range, and inadequate quantization levels, the applications of DMSP-OLS data are greatly limited by interannual inconsistency, saturation, and blooming problems. To address these issues, we used the power function model based on pseudo-invariant feature, the saturation correction method based on regression model and radiance-calibrated data (SARMRC), and the self-adjusting model (SEAM) to improve the quality of DMSP data, and generated a Consistent and Corrected Nighttime Light dataset (CCNL 1992–2013). CCNL dataset shows good performance in interannual consistency, spatial details of urban centers, and light blooming, which is helpful to fully explore the application potentials of long time series nighttime light data.
Genetic dissection of grain iron and zinc, and thousand kernel weight in wheat (Triticum aestivum L.) using genome-wide association study
Authors: Krishnappa Gopalareddy , Khan Hanif , Krishna Hari , Kumar Satish , Mishra Chandra Nath , Parkash Om , Devate Narayana Bhat , Nepolean Thirunavukkarasu , Rathan Nagenahalli Dharmegowda , Mamrutha Harohalli Masthigowda , Srivastava Puja , Biradar Suma , Uday Govindareddy , Kumar Monu , Singh Gyanendra , Singh Gyanendra Pratap 
Published: July 2022

AbstractGenetic biofortification is recognized as a cost-effective and sustainable strategy to reduce micronutrient malnutrition. Genomic regions governing grain iron concentration (GFeC), grain zinc concentration (GZnC), and thousand kernel weight (TKW) were investigated in a set of 280 diverse bread wheat genotypes. The genome-wide association (GWAS) panel was genotyped using 35 K Axiom Array and phenotyped in five environments. The GWAS analysis showed a total of 17 Bonferroni-corrected marker-trait associations (MTAs) in nine chromosomes representing all the three wheat subgenomes. The TKW showed the highest MTAs (7), followed by GZnC (5) and GFeC (5). Furthermore, 14 MTAs were identified with more than 10% phenotypic variation. One stable MTA i.e. AX-95025823 was identified for TKW in both E4 and E5 environments along with pooled data, which is located at 68.9 Mb on 6A chromosome. In silico analysis revealed that the SNPs were located on important putative candidate genes such as Multi antimicrobial extrusion protein, F-box domain, Late embryogenesis abundant protein, LEA-18, Leucine-rich repeat domain superfamily, and C3H4 type zinc finger protein, involved in iron translocation, iron and zinc homeostasis, and grain size modifications. The identified novel MTAs will be validated to estimate their effects in different genetic backgrounds for subsequent use in marker-assisted selection. The identified SNPs will be valuable in the rapid development of biofortified wheat varieties to ameliorate the malnutrition problems.
Locomotion of an untethered, worm-inspired soft robot driven by a shape-memory alloy skeleton
Authors: Xu Lin , Wagner Robert J. , Liu Siyuan , He Qingrui , Li Tao , Pan Wenlong , Feng Yu , Feng Huanhuan , Meng Qingguang , Zou Xiang , Fu Yu , Shi Xingling , Zhao Dongliang , Ding Jianning , Vernerey Franck J. 
Published: July 2022

AbstractSoft, worm-like robots show promise in complex and constrained environments due to their robust, yet simple movement patterns. Although many such robots have been developed, they either rely on tethered power supplies and complex designs or cannot move external loads. To address these issues, we here introduce a novel, maggot-inspired, magnetically driven “mag-bot” that utilizes shape memory alloy-induced, thermoresponsive actuation and surface pattern-induced anisotropic friction to achieve locomotion inspired by fly larvae. This simple, untethered design can carry cargo that weighs up to three times its own weight with only a 17% reduction in speed over unloaded conditions thereby demonstrating, for the first time, how soft, untethered robots may be used to carry loads in controlled environments. Given their small scale and low cost, we expect that these mag-bots may be used in remote, confined spaces for small objects handling or as components in more complex designs.
Nasal-spraying Bacillus spores as an effective symptomatic treatment for children with acute respiratory syncytial virus infection
Authors: Tran Dien Minh , Tran Tu Thanh , Phung Thuy Thi Bich , Bui Huyen Thi , Nguyen Phuc Thanh Thi , Vu Tam Thi , Ngo Nga Thi Phuong , Nguyen Mai Thi , Nguyen Anh Hoa , Nguyen Anh Thi Van 
Published: July 2022

AbstractRespiratory syncytial virus (RSV) is a leading cause of Acute Respiratory Tract Infections (ARTIs) in young children. However, there is currently no vaccine or treatment available for children. Here, we demonstrated that nasal-spraying probiotics containing 5 billion of Bacillus spores (LiveSpo Navax) is an effective symptomatic treatment in a 6-day randomized controlled clinical study for RSV-infected children (n = 40–46/group). Navax treatment resulted in 1-day faster recovery-time and 10–50% better efficacy in relieving ARTI symptoms. At day 3, RSV load and level of pro-inflammatory cytokines in nasopharyngeal samples was reduced by 630 folds and 2.7–12.7 folds respectively. This showed 53-fold and 1.8–3.6-fold more effective than those in the control-standard of care-group. In summary, nasal-spraying Bacillus spores can rapidly and effectively relieve symptoms of RSV-induced ARTIs while exhibit strong impacts in reducing viral load and inflammation. Our nasal-spraying probiotics may provide a basis for simple-to-use, low-cost, and effective treatment against viral infection in general.