bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel DSP zebrafish model reveals training- and drug-induced modulation of arrhythmogenic cardiomyopathy phenotypes
Authors: Celeghin Rudy , Risato Giovanni , Beffagna Giorgia , Cason Marco , Bueno Marinas Maria , Della Barbera Mila , Facchinello Nicola , Giuliodori Alice , Brañas Casas Raquel , Caichiolo Micol , Vettori Andrea , Grisan Enrico , Rizzo Stefania , Dalla Valle Luisa , Argenton Francesco , Thiene Gaetano , Tiso Natascia , Pilichou Kalliopi , Basso Cristina 
Published: December 2023

AbstractArrhythmogenic cardiomyopathy (AC) is an inherited disorder characterized by progressive loss of the ventricular myocardium causing life-threatening ventricular arrhythmias, syncope and sudden cardiac death in young and athletes. About 40% of AC cases carry one or more mutations in genes encoding for desmosomal proteins, including Desmoplakin (Dsp). We present here the first stable Dsp knock-out (KO) zebrafish line able to model cardiac alterations and cell signalling dysregulation, characteristic of the AC disease, on which environmental factors and candidate drugs can be tested. Our stable Dsp knock-out (KO) zebrafish line was characterized by cardiac alterations, oedema and bradycardia at larval stages. Histological analysis of mutated adult hearts showed reduced contractile structures and abnormal shape of the ventricle, with thinning of the myocardial layer, vessels dilation and presence of adipocytes within the myocardium. Moreover, TEM analysis revealed “pale”, disorganized and delocalized desmosomes. Intensive physical training protocol caused a global worsening of the cardiac phenotype, accelerating the progression of the disease. Of note, we detected a decrease of Wnt/β-catenin signalling, recently associated with AC pathogenesis, as well as Hippo/YAP-TAZ and TGF-β pathway dysregulation. Pharmacological treatment of mutated larvae with SB216763, a Wnt/β-catenin agonist, rescued pathway expression and cardiac abnormalities, stabilizing the heart rhythm. Overall, our Dsp KO zebrafish line recapitulates many AC features observed in human patients, pointing at zebrafish as a suitable system for in vivo analysis of environmental modulators, such as the physical exercise, and the screening of pathway-targeted drugs, especially related to the Wnt/β-catenin signalling cascade.
Atg18 oligomer organization in assembled tubes and on lipid membrane scaffolds
Authors: Mann Daniel , Fromm Simon A. , Martinez-Sanchez Antonio , Gopaldass Navin , Choy Ramona , Mayer Andreas , Sachse Carsten 
Published: December 2023

AbstractAutophagy-related protein 18 (Atg18) participates in the elongation of early autophagosomal structures in concert with Atg2 and Atg9 complexes. How Atg18 contributes to the structural coordination of Atg2 and Atg9 at the isolation membrane remains to be understood. Here, we determined the cryo-EM structures of Atg18 organized in helical tubes, Atg18 oligomers in solution as well as on lipid membrane scaffolds. The helical assembly is composed of Atg18 tetramers forming a lozenge cylindrical lattice with remarkable structural similarity to the COPII outer coat. When reconstituted with lipid membranes, using subtomogram averaging we determined tilted Atg18 dimer structures bridging two juxtaposed lipid membranes spaced apart by 80 Å. Moreover, lipid reconstitution experiments further delineate the contributions of Atg18’s FRRG motif and the amphipathic helical extension in membrane interaction. The observed structural plasticity of Atg18’s oligomeric organization and membrane binding properties provide a molecular framework for the positioning of downstream components of the autophagy machinery.
The PENGUIN approach to reconstruct protein interactions at enhancer-promoter regions and its application to prostate cancer
Authors: Armaos Alexandros , Serra François , Núñez-Carpintero Iker , Seo Ji-Heui , Baca Sylvan C. , Gustincich Stefano , Valencia Alfonso , Freedman Matthew L. , Cirillo Davide , Giambartolomei Claudia , Tartaglia Gian Gaetano 
Published: December 2023

AbstractWe introduce Promoter-Enhancer-Guided Interaction Networks (PENGUIN), a method for studying protein-protein interaction (PPI) networks within enhancer-promoter interactions. PENGUIN integrates H3K27ac-HiChIP data with tissue-specific PPIs to define enhancer-promoter PPI networks (EPINs). We validated PENGUIN using cancer (LNCaP) and benign (LHSAR) prostate cell lines. Our analysis detected EPIN clusters enriched with the architectural protein CTCF, a regulator of enhancer-promoter interactions. CTCF presence was coupled with the prevalence of prostate cancer (PrCa) single nucleotide polymorphisms (SNPs) within the same EPIN clusters, suggesting functional implications in PrCa. Within the EPINs displaying enrichments in both CTCF and PrCa SNPs, we also show enrichment in oncogenes. We substantiated our identified SNPs through CRISPR/Cas9 knockout and RNAi screens experiments. Here we show that PENGUIN provides insights into the intricate interplay between enhancer-promoter interactions and PPI networks, which are crucial for identifying key genes and potential intervention targets. A dedicated server is available at https://penguin.life.bsc.es/.
Performance boost for bismuth telluride thermoelectric generator via barrier layer based on low Young’s modulus and particle sliding
Authors: Sun Yuxin , Guo Fengkai , Feng Yan , Li Chun , Zou Yongchun , Cheng Jinxuan , Dong Xingyan , Wu Hao , Zhang Qian , Liu Weishu , Liu Zihang , Cai Wei , Ren Zhifeng , Sui Jiehe 
Published: December 2023

AbstractThe lack of desirable diffusion barrier layers currently prohibits the long-term stable service of bismuth telluride thermoelectric devices in low-grade waste heat recovery. Here we propose a new design principle of barrier layers beyond the thermal expansion matching criterion. A titanium barrier layer with loose structure is optimized, in which the low Young’s modulus and particle sliding synergistically alleviates interfacial stress, while the TiTe2 reactant enables metallurgical bonding and ohmic contact between the barrier layer and the thermoelectric material, leading to a desirable interface characterized by high-thermostability, high-strength, and low-resistivity. Highly competitive conversion efficiency of 6.2% and power density of 0.51 W cm−2 are achieved for a module with leg length of 2 mm at the hot-side temperature of 523 K, and no degradation is observed following operation for 360 h, a record for stable service at this temperature, paving the way for its application in low-grade waste heat recovery.
A human embryonic limb cell atlas resolved in space and time
Authors: Zhang Bao , He Peng , Lawrence John E. G. , Wang Shuaiyu , Tuck Elizabeth , Williams Brian A. , Roberts Kenny , Kleshchevnikov Vitalii , Mamanova Lira , Bolt Liam , Polanski Krzysztof , Li Tong , Elmentaite Rasa , Fasouli Eirini S. , Prete Martin , He Xiaoling , Yayon Nadav , Fu Yixi , Yang Hao , Liang Chen , Zhang Hui , Blain Raphael , Chedotal Alain , FitzPatrick David R. , Firth Helen , Dean Andrew , Bayraktar Omer Ali , Marioni John C. , Barker Roger A. , Storer Mekayla A. , Wold Barbara J. , Zhang Hongbo , Teichmann Sarah A. 
Published: December 2023

AbstractHuman limbs emerge during the fourth post-conception week as mesenchymal buds, which develop into fully formed limbs over the subsequent months1. This process is orchestrated by numerous temporally and spatially restricted gene expression programmes, making congenital alterations in phenotype common2. Decades of work with model organisms have defined the fundamental mechanisms underlying vertebrate limb development, but an in-depth characterization of this process in humans has yet to be performed. Here we detail human embryonic limb development across space and time using single-cell and spatial transcriptomics. We demonstrate extensive diversification of cells from a few multipotent progenitors to myriad differentiated cell states, including several novel cell populations. We uncover two waves of human muscle development, each characterized by different cell states regulated by separate gene expression programmes, and identify musculin (MSC) as a key transcriptional repressor maintaining muscle stem cell identity. Through assembly of multiple anatomically continuous spatial transcriptomic samples using VisiumStitcher, we map cells across a sagittal section of a whole fetal hindlimb. We reveal a clear anatomical segregation between genes linked to brachydactyly and polysyndactyly, and uncover transcriptionally and spatially distinct populations of the mesenchyme in the autopod. Finally, we perform single-cell RNA sequencing on mouse embryonic limbs to facilitate cross-species developmental comparison, finding substantial homology between the two species.
Logical quantum processor based on reconfigurable atom arrays
Authors: Bluvstein Dolev , Evered Simon J. , Geim Alexandra A. , Li Sophie H. , Zhou Hengyun , Manovitz Tom , Ebadi Sepehr , Cain Madelyn , Kalinowski Marcin , Hangleiter Dominik , Bonilla Ataides J. Pablo , Maskara Nishad , Cong Iris , Gao Xun , Sales Rodriguez Pedro , Karolyshyn Thomas , Semeghini Giulia , Gullans Michael J. , Greiner Markus , Vuletić Vladan , Lukin Mikhail D. 
Published: December 2023

AbstractSuppressing errors is the central challenge for useful quantum computing1, requiring quantum error correction (QEC)2–6for large-scale processing. However, the overhead in the realization of error-corrected ‘logical’ qubits, in which information is encoded across many physical qubits for redundancy2–4, poses substantial challenges to large-scale logical quantum computing. Here we report the realization of a programmable quantum processor based on encoded logical qubits operating with up to 280 physical qubits. Using logical-level control and a zoned architecture in reconfigurable neutral-atom arrays7, our system combines high two-qubit gate fidelities8, arbitrary connectivity7,9, as well as fully programmable single-qubit rotations and mid-circuit readout10–15. Operating this logical processor with various types of encoding, we demonstrate improvement of a two-qubit logic gate by scaling surface-code6distance fromd = 3 tod = 7, preparation of colour-code qubits with break-even fidelities5, fault-tolerant creation of logical Greenberger–Horne–Zeilinger (GHZ) states and feedforward entanglement teleportation, as well as operation of 40 colour-code qubits. Finally, using 3D [[8,3,2]] code blocks16,17, we realize computationally complex sampling circuits18with up to 48 logical qubits entangled with hypercube connectivity19with 228 logical two-qubit gates and 48 logical CCZ gates20. We find that this logical encoding substantially improves algorithmic performance with error detection, outperforming physical-qubit fidelities at both cross-entropy benchmarking and quantum simulations of fast scrambling21,22. These results herald the advent of early error-corrected quantum computation and chart a path towards large-scale logical processors.
Linear energy transfer (LET) distribution outside small radiotherapy field edges produced by 6 MV X-rays
Authors: Huerta-Juan Y. , Xicohténcatl-Hernández N. , Massillon-JL G. 
Published: December 2023

AbstractIn modern radiotherapy with photons, the absorbed dose outside the radiation field is generally investigated. But it is well known that the biological damage depends not only on the absorbed dose but also on LET. This work investigated the dose-average LET (LΔ,D) outside several small radiotherapy fields to provide information that can help for better evaluating the biological effect in organs at risk close to the tumour volume. The electron fluences produced in liquid water by a 6 MV X-rays Varian iX linac were calculated using the EGSnrc Monte Carlo code. With the electron spectra, LΔ,D calculations were made for eight open small square fields and the reference field at water depths of 0.15 cm, 1.35 cm, 9.85 cm and 19.85 cm and several off-axis distances. The variation of LΔ,D from the centre of the beam to 2 cm outside the field’s edge depends on the field size and water depth. Using radiobiological data reported in the literature for chromosomal aberrations as an endpoint for the induction of dicentrics determined in Human Lymphocytes, we estimated the maximum low-dose relative biological effectiveness, (RBEM) finding an increase of up to 100% from the centre of the beam to 2 cm from the field's edge.
Increased circulating progranulin is not sufficient to induce cardiac dysfunction or supraventricular arrhythmia
Authors: McElhanon Kevin E. , Huff Tyler C. , Hirenallur-Shanthappa Dinesh , Miller Russell A. , Christoforou Nicolas 
Published: December 2023

AbstractAtrial fibrillation (AF) is the most prevalent cardiac arrhythmia, and the incidence of new-onset AF has been increasing over the past two decades. Several factors contribute to the risk of developing AF including age, preexisting cardiovascular disease, chronic kidney disease, and obesity. Concurrent with the rise in AF, obesity has followed the same two-decade trend. The contribution of circulating proteins to obesity-related AF is of particular interest in the field. In this study, we investigated the effects of increased circulating levels of the glycoprotein progranulin on the development of supraventricular arrhythmias and changes to cardiac function. AAV8-mediated overexpression of full-length mouse progranulin was used to increase plasma protein levels and determine susceptibility to supraventricular arrhythmias and changes in cardiac structure and function. C57Bl/6N mice were subjected to increased circulating levels of progranulin for 20 weeks. Cardiac conduction was evaluated by surface ECG with and without isoproterenol challenge, and cardiac structure and function were measured by echocardiography after 20 weeks of circulating progranulin overexpression. Increased circulating levels of progranulin were maintained throughout the 20-week study. The cardiac structure and function remained unchanged in mice with increased circulating progranulin. ECG indices (P wave duration, P amplitude, QRS interval) were unaffected by increased progranulin levels and no arrhythmogenic events were observed following the isoproterenol challenge. In our model, increased levels of circulating progranulin were not sufficient to induce changes in cardiac structure and function or elicit ECG abnormalities suggestive of susceptibility to supraventricular arrhythmias.
A novel invasive Streptococcus pyogenes variant sublineage derived through recombinational replacement of the emm12 genomic region
Authors: Unoarumhi Yvette , Davis Morgan L. , Rowe Lori A. , Mathis Saundra , Li Zhongya , Chochua Sopio , Li Yuan , McGee Lesley , Metcalf Benjamin J. , Lee Justin S. , Beall Bernard 
Published: December 2023

AbstractGroup A streptococcal strains potentially acquire new M protein gene types through genetic recombination (emm switching). To detect such variants, we screened 12,596 invasive GAS genomes for strains of differing emm types that shared the same multilocus sequence type (ST). Through this screening we detected a variant consisting of 16 serum opacity factor (SOF)-positive, emm pattern E, emm82 isolates that were ST36, previously only associated with SOF-negative, emm pattern A, emm12. The 16 emm82/ST36 isolates were closely interrelated (pairwise SNP distance of 0–43), and shared the same emm82-containing recombinational fragment. emm82/ST36 isolates carried the sof12 structural gene, however the sof12 indel characteristic of emm12 strains was corrected to confer the SOF-positive phenotype. Five independent emm82/ST36 invasive case isolates comprised two sets of genetically indistinguishable strains. The emm82/ST36 isolates were primarily macrolide resistant (12/16 isolates), displayed at least 4 different core genomic arrangements, and carried 11 different combinations of virulence and resistance determinants. Phylogenetic analysis revealed that emm82/ST36 was within a minor (non-clade 1) portion of ST36 that featured almost all ST36 antibiotic resistance. This work documents emergence of a rapidly diversifying variant that is the first confirmed example of an emm pattern A strain switched to a pattern E strain.
Phase variation of manganese oxide in the MnO@ZnO nanocomposite with calcination temperature and its effect on structural and biological activities
Authors: Basak Shatarupa , Haydar Md Salman , Sikdar Suranjan , Ali Salim , Mondal Modhusudan , Shome Ankita , Sarkar Kushankur , Roy Swarnendu , Roy Mahendra Nath 
Published: December 2023

AbstractHaving powerful antibacterial and antioxidant effects, zinc oxide and manganese oxide nanomaterials are of great interest. Here we have synthesized manganese oxide decorated zinc oxide (MZO) nanocomposites by co-precipitation method, calcined at different temperatures (300–750 °C) and studied various properties. Here the crystalline structure of the nanocomposite and phase change of the manganese oxide are observed with calcination temperature. The average crystalline size increases and the dislocation density and microstrain decrease with the increase in calcined temperature for the same structural features. The formation of composites was confirmed by XRD pattern and SEM images. EDAX spectra proved the high purity of the composites. Here, different biological properties change with the calcination temperature for different shapes, sizes and structures of the nanocomposite. Nanomaterial calcined at 750 °C provides the best anti-microbial activity against Escherichia coli, Salmonella typhimurium, Shigella flexneri (gram-negative), Bacillus subtilis and Bacillus megaterium (gram-positive) bacterial strain at 300 µg/mL concentration. The nanomaterial with calcination temperatures of 300 °C and 450 °C provided better antioxidant properties.
Prioritizing biomaterials for spinal disc implants by a fuzzy AHP and TOPSIS decision making method
Authors: Ansaripour Hossein , Haeussler Kim Lars , Ferguson Stephen J. , Flohr Markus 
Published: December 2023

AbstractConsiderable research has been focused on identifying the optimum biomaterial for spine implants. New technologies and materials have allowed surgeons to better grasp the biomechanical principles underpinning implant stability and function. An optimal biomaterial for total disc replacement (TDR) should include essential characteristics such as biocompatibility, long-term durability, the capacity to withstand mechanical stresses, and economic viability. Our research has focused on six biomaterials for TDR, including Ti–6Al–4V, CoCr alloy, stainless steel 316L, zirconia toughened alumina (ZTA), polyether ether ketone (PEEK) and ultra-high-molecular weight polyethylene (UHMWPE). Ten common properties, i.e., the Young’s modulus, density, tensile strength, the expense of the manufacturing process, the cost of raw material, wear rate, corrosion resistance, thermal conductivity, fracture toughness and compressive strength were utilized to assess these six different materials. The purpose of this study was to evaluate and rank the six alternative biomaterials proposed for use in the endplates and articulating surface of a spinal TDR. To accomplish this, a multi-criteria decision-making approach, namely the fuzzy analytic hierarchy process (fuzzy AHP) and the Technique of Order Preference by Similarity to Ideal Solution (TOPSIS) was adopted to solve the model. For validation and robustness of the proposed method, sensitivity analysis was performed, and comparison was performed with fuzzy-VIKOR and fuzzy-MOORA methods. In light of the study’s results, ZTA and Ti–6Al–4V were identified as the best suited materials for the articulating surface and endplates, respectively, in a spinal disc implant.
Multimodal optical clearing to minimize light attenuation in biological tissues
Authors: Shariati B. K. Behnam , Ansari Mohammad Ali , Khatami Seyyede Sarvenaz , Tuchin Valery V. 
Published: December 2023

AbstractThe biggest obstacle to optical imaging is light attenuation in biological tissues. Conventional clearing techniques, such as agent-based clearing, improve light penetration depth by reducing scattering, but they are hampered by drawbacks including toxicity, low efficiency, slowness, and superficial performance, which prevent them from resolving the attenuation problem on their own. Therefore, quick, safe, and effective procedures have been developed. One of them involves using standing ultrasonic waves to build light waveguides that function effectively in the tissue depth while minimizing scattering. Temporal optical clearing is another agent-free strategy that we introduced in our previous article. Whereas not deep, this technique minimizes both light absorption and scattering by pulse width variation in ultra-short pulse regime. Consequently, it can be a complementary method for ultrasonic optical clearing. In this work, we enhanced the light penetration depth in chicken breast tissue by 10 times (0.67–6.7 cm), setting a record in literature by integrating three clearing methods: agent-based, ultrasound-based, and temporal. Here, optical coherence tomography, Bear–Lambert, and fluorescence tests have been used to study the light penetration depth and optical clearing efficiency. Presented work is an essential step in development of diagnostic techniques for human body, from cells to organs.
Long and isolated graphene nanoribbons by on-surface polymerization on Au(111)
Authors: Thupakula Umamahesh , Soe We-Hyo , Joachim Christian , Dujardin Erik 
Published: December 2023

AbstractLow electronic gap graphene nanoribbons (GNRs) are used for the fabrication of nanomaterial-based devices and, when isolated, for mono-molecular electronics experiences, for which a well-controlled length is crucial. Here, an on-surface chemistry protocol is monitored for producing long and well-isolated GNR molecular wires on an Au(111) surface. The two-step Ullmann coupling reaction is sequenced in temperature from 100 °C to 350 °C by steps of 50 °C, returning at room temperature between each step and remaining in ultrahigh vacuum conditions. After the first annealing step at 100 °C, the monomers self-organize into 2-monolayered nano-islands. Next, the Ullmann coupling reaction takes place in both 1st and 2nd layers of those nano-islands. The nano-island lateral size and shape are controlling the final GNR lengths. Respecting the above on-surface chemistry protocol, an optimal initial monomer coverage of ~1.5 monolayer produces isolated GNRs with a final length distribution reaching up to 50 nm and a low surface coverage of ~0.4 monolayer suitable for single molecule experiments.
High shear flow prevents bundling of bacterial flagella and induces lateral migration away from a wall
Authors: Yang Jinyou , Kikuchi Kenji , Ishikawa Takuji 
Published: December 2023

AbstractSince the discovery of bacteria in the 17th century, bacterial motion has been the focus of great research interest. As an example of bacterial chemotaxis, Escherichia coli exhibits run-and-tumble motion by bundling and unbundling flagella, propelling the cells along a concentration gradient. However, the behavior of bacteria in high-shear flow environments remains poorly understood. In this study, we showed experimentally that E. coli swimming is severely inhibited at shear rates above a few hundred per second. Our simulations revealed that E. coli flagellar bundling cannot occur in a high-shear regime, because the background shear flow is stronger than the flagellar-generated flow required to form a bundle. Bacteria under strong shear behave like deformable objects and exhibit lateral migration away from a wall. These results suggest that bacteria that are unable to bundle their flagella in strong shear near a wall alter their locomotion strategy to passively escape from the wall.