bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intrinsically disordered CsoS2 acts as a general molecular thread for α-carboxysome shell assembly
Authors: Ni Tao , Jiang Qiuyao , Ng Pei Cing , Shen Juan , Dou Hao , Zhu Yanan , Radecke Julika , Dykes Gregory F. , Huang Fang , Liu Lu-Ning , Zhang Peijun 
Published: September 2023

AbstractCarboxysomes are a paradigm of self-assembling proteinaceous organelles found in nature, offering compartmentalisation of enzymes and pathways to enhance carbon fixation. In α-carboxysomes, the disordered linker protein CsoS2 plays an essential role in carboxysome assembly and Rubisco encapsulation. Its mechanism of action, however, is not fully understood. Here we synthetically engineer α-carboxysome shells using minimal shell components and determine cryoEM structures of these to decipher the principle of shell assembly and encapsulation. The structures reveal that the intrinsically disordered CsoS2 C-terminus is well-structured and acts as a universal “molecular thread” stitching through multiple shell protein interfaces. We further uncover in CsoS2 a highly conserved repetitive key interaction motif, [IV]TG, which is critical to the shell assembly and architecture. Our study provides a general mechanism for the CsoS2-governed carboxysome shell assembly and cargo encapsulation and further advances synthetic engineering of carboxysomes for diverse biotechnological applications.
Deciphering complex breakage-fusion-bridge genome rearrangements with Ambigram
Authors: Li Chaohui , Chen Lingxi , Pan Guangze , Zhang Wenqian , Li Shuai Cheng 
Published: September 2023

AbstractBreakage-fusion-bridge (BFB) is a complex rearrangement that leads to tumor malignancy. Existing models for detecting BFBs rely on the ideal BFB hypothesis, ruling out the possibility of BFBs entangled with other structural variations, that is, complex BFBs. We propose an algorithm Ambigram to identify complex BFB and reconstruct the rearranged structure of the local genome during the cancer subclone evolution process. Ambigram handles data from short, linked, long, and single-cell sequences, and optical mapping technologies. Ambigram successfully deciphers the gold- or silver-standard complex BFBs against the state-of-the-art in multiple cancers. Ambigram dissects the intratumor heterogeneity of complex BFB events with single-cell reads from melanoma and gastric cancer. Furthermore, applying Ambigram to liver and cervical cancer data suggests that the BFB mechanism may mediate oncovirus integrations. BFB also exists in noncancer genomics. Investigating the complete human genome reference with Ambigram suggests that the BFB mechanism may be involved in two genome reorganizations of Homo Sapiens during evolution. Moreover, Ambigram discovers the signals of recurrent foldback inversions and complex BFBs in whole genome data from the 1000 genome project, and congenital heart diseases, respectively.
Organic laser power converter for efficient wireless micro power transfer
Authors: Wang Yafei , Zheng Zhong , Wang Jianqiu , Bi Pengqing , Chen Zhihao , Ren Junzhen , An Cunbin , Zhang Shaoqing , Hou Jianhui 
Published: September 2023

AbstractWireless power transfer with collimated power transmission and efficient conversion provides an alternative charging mode for off-grid and portable micro-power electronics. However, charging micro-power electronics with low photon flux can be challenging for current laser power converters. Here we show laser power converters with organic photovoltaic cells with good performance for application in laser wireless power transfer. The laser selection strategy is established and the upper limit of efficiency is proposed. The organic laser power converters exhibit a 36.2% efficiency at a 660 nm laser with a photon flux of 9.5 mW cm−2and achieve wireless micro power transfer with an output of 0.5 W on a 2 meter scale. This work shows the good performance of organic photovoltaic cells in constructing organic laser power converters and provides a potential solution for the wireless power transfer of micro-power electronics.
Phase separation of protein mixtures is driven by the interplay of homotypic and heterotypic interactions
Authors: Farag Mina , Borcherds Wade M. , Bremer Anne , Mittag Tanja , Pappu Rohit V. 
Published: September 2023

AbstractPrion-like low-complexity domains (PLCDs) are involved in the formation and regulation of distinct biomolecular condensates that form via phase separation coupled to percolation. Intracellular condensates often encompass numerous distinct proteins with PLCDs. Here, we combine simulations and experiments to study mixtures of PLCDs from two RNA-binding proteins, hnRNPA1 and FUS. Using simulations and experiments, we find that 1:1 mixtures of A1-LCD and FUS-LCD undergo phase separation more readily than either of the PLCDs on their own due to complementary electrostatic interactions. Tie line analysis reveals that stoichiometric ratios of different components and their sequence-encoded interactions contribute jointly to the driving forces for condensate formation. Simulations also show that the spatial organization of PLCDs within condensates is governed by relative strengths of homotypic versus heterotypic interactions. We uncover rules for how interaction strengths and sequence lengths modulate conformational preferences of molecules at interfaces of condensates formed by mixtures of proteins.
All-round catalytic and atroposelective strategy via dynamic kinetic resolution for N-/2-/3-arylindoles
Authors: Kim Ahreum , Lee Chanhee , Song Jayoung , Lee Sang Kook , Kwon Yongseok 
Published: September 2023

AbstractAs the complexity of organic molecules utilized by mankind increases, the phenomenon of atropisomerism is more frequently encountered. While a variety of well-established methods enable the control of a stereogenic center, a catalytic method for controlling a stereogenic axis in one substrate is typically unavailable for controlling axial chirality in other substrates with a similar structure. Herein, we report o-amidobiaryl as a flexible platform for chiral phosphoric acid-catalyzed atroposelective dynamic kinetic resolution. To demonstrate our strategy, three distinct types of arylindoles were utilized and reacted intermolecularly with ketomalonate in the presence of chiral phosphoric acid. An investigation of 46 substrates having an aromatic ring in different positions yields the desired products with excellent enantioselectivities. Computational investigation into the origin of enantioselectivity highlights the importance of the NH group. Given the biological significance of indoles, antiproliferative effects have been investigated; our scaffold exhibits good efficacy in this regard.
Peroxisomal compartmentalization of amino acid biosynthesis reactions imposes an upper limit on compartment size
Authors: Gu Ying , Alam Sara , Oliferenko Snezhana 
Published: September 2023

AbstractCellular metabolism relies on just a few redox cofactors. Selective compartmentalization may prevent competition between metabolic reactions requiring the same cofactor. Is such compartmentalization necessary for optimal cell function? Is there an optimal compartment size? Here we probe these fundamental questions using peroxisomal compartmentalization of the last steps of lysine and histidine biosynthesis in the fission yeast Schizosaccharomyces japonicus. We show that compartmentalization of these NAD+ dependent reactions together with a dedicated NADH/NAD+ recycling enzyme supports optimal growth when an increased demand for anabolic reactions taxes cellular redox balance. In turn, compartmentalization constrains the size of individual organelles, with larger peroxisomes accumulating all the required enzymes but unable to support both biosynthetic reactions at the same time. Our reengineering and physiological experiments indicate that compartmentalized biosynthetic reactions are sensitive to the size of the compartment, likely due to scaling-dependent changes within the system, such as enzyme packing density.
Quantitative whole-tissue 3D imaging reveals bacteria in close association with mouse jejunum mucosa
Authors: Poceviciute Roberta , Bogatyrev Said R. , Romano Anna E. , Dilmore Amanda H. , Mondragón-Palomino Octavio , Takko Heli , Pradhan Ojas , Ismagilov Rustem F. 
Published: September 2023

AbstractBecause the small intestine (SI) epithelium lacks a thick protective mucus layer, microbes that colonize the thin SI mucosa may exert a substantial effect on the host. For example, bacterial colonization of the human SI may contribute to environmental enteropathy dysfunction (EED) in malnourished children. Thus far, potential bacterial colonization of the mucosal surface of the SI has only been documented in disease states, suggesting mucosal colonization is rare, likely requiring multiple perturbations. Furthermore, conclusive proof of bacterial colonization of the SI mucosal surface is challenging, and the three-dimensional (3D) spatial structure of mucosal colonies remains unknown. Here, we tested whether we could induce dense bacterial association with jejunum mucosa by subjecting mice to a combination of malnutrition and oral co-gavage with a bacterial cocktail (E. coliandBacteroidesspp.) known to induce EED. To visualize these events, we optimized our previously developed whole-tissue 3D imaging tools with third-generation hybridization chain reaction (HCR v3.0) probes. Only in mice that were malnourished and gavaged with the bacterial cocktail did we detect dense bacterial clusters surrounding intestinal villi suggestive of colonization. Furthermore, in these mice we detected villus loss, which may represent one possible consequence that bacterial colonization of the SI mucosa has on the host. Our results suggest that dense bacterial colonization of jejunum mucosa is possible in the presence of multiple perturbations and that whole-tissue 3D imaging tools can enable the study of these rare events.
Phase field modeling with large driving forces
Authors: Zhang Jin , Chadwick Alexander F. , Chopp David L. , Voorhees Peter W. 
Published: September 2023

AbstractThere is growing interest in applying phase field methods as quantitative tools in materials discovery and development. However, large driving forces, common in many materials systems, lead to unstable phase field profiles, thus requiring fine spatial and temporal resolution. This demands more computational resources, limits the ability to simulate systems with a suitable size, and deteriorates the capability of quantitative prediction. Here, we develop a strategy to map the driving force to a constant perpendicular to the interface. Together with the third-order interpolation function, we find a stable phase field profile that is independent of the magnitude of the driving force. The power of this approach is illustrated using three models. We demonstrate that by using the driving force extension method, it is possible to employ a grid size orders of magnitude larger than traditional methods. This approach is general and should apply to many other phase field models.
Evaluation of free-floating tracheal intubation in weightlessness via ice-pick position with a direct laryngoscopy and classic approach with indirect videolaryngoscopy
Authors: Thierry Séamus , Jaulin François , Starck Clément , Ariès Philippe , Schmitz Jan , Kerkhoff Steffen , Bernard Cécile Isabelle , Komorowski Matthieu , Warnecke Tobias , Hinkelbein Jochen 
Published: September 2023

AbstractLong duration spaceflights to the Moon or Mars are at risk for emergency medical events. Managing a hypoxemic distress and performing an advanced airway procedure such as oro-tracheal intubation may be complicated under weightlessness due to ergonomic constraints. An emergency free-floating intubation would be dangerous because of high failure rates due to stabilization issues that prohibits its implementation in a space environment. Nevertheless, we hypothesized that two configurations could lead to a high first-pass success score for intubation performed by a free-floating operator. In a non-randomized, controlled, cross-over simulation study during a parabolic flight campaign, we evaluated and compared the intubation performance of free-floating trained operators, using either a conventional direct laryngoscope in an ice-pick position or an indirect laryngoscopy with a video-laryngoscope in a classic position at the head of a high-fidelity simulation manikin, in weightlessness and in normogravity. Neither of the two tested conditions reached the minimal terrestrial ILCOR recommendations (95% first-pass success) and therefore could not be recommended for general implementation under weightlessness conditions. Free-floating video laryngoscopy at the head of the manikin had a significant better success score than conventional direct laryngoscopy in an ice-pick position. Our results, combined with the preexisting literature, emphasis the difficulties of performing oro-tracheal intubation, even for experts using modern airway devices, under postural instability in weightlessness. ClinicalTrials registration number NCT05303948.
Quantitative systems-based prediction of antimicrobial resistance evolution
Authors: Charlebois Daniel A. 
Published: September 2023

AbstractPredicting evolution is a fundamental problem in biology with practical implications for treating antimicrobial resistance, which is a complex system-level phenomenon. In this perspective article, we explore the limits of predicting antimicrobial resistance evolution, quantitatively define the predictability and repeatability of microevolutionary processes, and speculate on how these quantities vary across temporal, biological, and complexity scales. The opportunities and challenges for predicting antimicrobial resistance in the context of systems biology are also discussed. Based on recent research, we conclude that the evolution of antimicrobial resistance can be predicted using a systems biology approach integrating quantitative models with multiscale data from microbial evolution experiments.
A mosaic influenza virus-like particles vaccine provides broad humoral and cellular immune responses against influenza A viruses
Authors: Liu Xuejie , Zhao Tianyi , Wang Liangliang , Yang Zhuolin , Luo Chuming , Li Minchao , Luo Huanle , Sun Caijun , Yan Huacheng , Shu Yuelong 
Published: September 2023

AbstractThe development of a universal influenza vaccine to elicit broad immune responses is essential in reducing disease burden and pandemic impact. In this study, the mosaic vaccine design strategy and genetic algorithms were utilized to optimize the seasonal influenza A virus (H1N1, H3N2) hemagglutinin (HA) and neuraminidase (NA) antigens, which also contain most potential T-cell epitopes. These mosaic immunogens were then expressed as virus-like particles (VLPs) using the baculovirus expression system. The immunogenicity and protection effectiveness of the mosaic VLPs were compared to the commercial quadrivalent inactivated influenza vaccine (QIV) in the mice model. Strong cross-reactive antibody responses were observed in mice following two doses of vaccination with the mosaic VLPs, with HI titers higher than 40 in 15 of 16 tested strains as opposed to limited cross HI antibody levels with QIV vaccination. After a single vaccination, mice also show a stronger level of cross-reactive antibody responses than the QIV. The QIV vaccinations only elicited NI antibodies to a small number of vaccine strains, and not even strong NI antibodies to its corresponding vaccine components. In contrast, the mosaic VLPs caused robust NI antibodies to all tested seasonal influenza virus vaccine strains. Here, we demonstrated the mosaic vaccines induces stronger cross-reactive antibodies and robust more T-cell responses compared to the QIV. The mosaic VLPs also provided protection against challenges with ancestral influenza A viruses of both H1 and H3 subtypes. These findings indicated that the mosaic VLPs were a promising strategy for developing a broad influenza vaccine in future.
Design principles for cyclin K molecular glue degraders
Authors: Kozicka Zuzanna , Suchyta Dakota J. , Focht Vivian , Kempf Georg , Petzold Georg , Jentzsch Marius , Zou Charles , Di Genua Cristina , Donovan Katherine A. , Coomar Seemon , Cigler Marko , Mayor-Ruiz Cristina , Schmid-Burgk Jonathan L. , Häussinger Daniel , Winter Georg E. , Fischer Eric S. , Słabicki Mikołaj , Gillingham Dennis , Ebert Benjamin L. , Thomä Nicolas H. 
Published: September 2023

AbstractMolecular glue degraders are an effective therapeutic modality, but their design principles are not well understood. Recently, several unexpectedly diverse compounds were reported to deplete cyclin K by linking CDK12–cyclin K to the DDB1–CUL4–RBX1 E3 ligase. Here, to investigate how chemically dissimilar small molecules trigger cyclin K degradation, we evaluated 91 candidate degraders in structural, biophysical and cellular studies and reveal all compounds acquire glue activity via simultaneous CDK12 binding and engagement of DDB1 interfacial residues, in particular Arg928. While we identify multiple published kinase inhibitors as cryptic degraders, we also show that these glues do not require pronounced inhibitory properties for activity and that the relative degree of CDK12 inhibition versus cyclin K degradation is tuneable. We further demonstrate cyclin K degraders have transcriptional signatures distinct from CDK12 inhibitors, thereby offering unique therapeutic opportunities. The systematic structure–activity relationship analysis presented herein provides a conceptual framework for rational molecular glue design.
Regulation with cell size ensures mitochondrial DNA homeostasis during cell growth
Authors: Seel Anika , Padovani Francesco , Mayer Moritz , Finster Alissa , Bureik Daniela , Thoma Felix , Osman Christof , Klecker Till , Schmoller Kurt M. 
Published: September 2023

AbstractTo maintain stable DNA concentrations, proliferating cells need to coordinate DNA replication with cell growth. For nuclear DNA, eukaryotic cells achieve this by coupling DNA replication to cell-cycle progression, ensuring that DNA is doubled exactly once per cell cycle. By contrast, mitochondrial DNA replication is typically not strictly coupled to the cell cycle, leaving the open question of how cells maintain the correct amount of mitochondrial DNA during cell growth. Here, we show that in budding yeast, mitochondrial DNA copy number increases with cell volume, both in asynchronously cycling populations and during G1 arrest. Our findings suggest that cell-volume-dependent mitochondrial DNA maintenance is achieved through nuclear-encoded limiting factors, including the mitochondrial DNA polymerase Mip1 and the packaging factor Abf2, whose amount increases in proportion to cell volume. By directly linking mitochondrial DNA maintenance to nuclear protein synthesis and thus cell growth, constant mitochondrial DNA concentrations can be robustly maintained without a need for cell-cycle-dependent regulation.
A review of the machine learning datasets in mammography, their adherence to the FAIR principles and the outlook for the future
Authors: Logan Joe , Kennedy Paul J. , Catchpoole Daniel 
Published: September 2023

AbstractThe increasing rates of breast cancer, particularly in emerging economies, have led to interest in scalable deep learning-based solutions that improve the accuracy and cost-effectiveness of mammographic screening. However, such tools require large volumes of high-quality training data, which can be challenging to obtain. This paper combines the experience of an AI startup with an analysis of the FAIR principles of the eight available datasets. It demonstrates that the datasets vary considerably, particularly in their interoperability, as each dataset is skewed towards a particular clinical use-case. Additionally, the mix of digital captures and scanned film compounds the problem of variability, along with differences in licensing terms, ease of access, labelling reliability, and file formats. Improving interoperability through adherence to standards such as the BIRADS criteria for labelling and annotation, and a consistent file format, could markedly improve access and use of larger amounts of standardized data. This, in turn, could be increased further by GAN-based synthetic data generation, paving the way towards better health outcomes for breast cancer.
A chromosome-level genome assembly of the darkbarbel catfish Pelteobagrus vachelli
Authors: Gong Gaorui , Ke Wensi , Liao Qian , Xiong Yang , Hu Jingqi , Mei Jie 
Published: September 2023

AbstractThe darkbarbel catfish (Pelteobagrus vachelli), an economically important aquaculture species in China, is extensively employed in hybrid yellow catfish production due to its superior growth rate. However, information on its genome has been limited, constraining further genetic studies and breeding programs. Leveraging the power of PacBio long-read sequencing and Hi-C technologies, we present a high-quality, chromosome-level genome assembly for the darkbarbel catfish. The resulting assembly spans 692.10 Mb, with an impressive 99.9% distribution over 26 chromosomes. The contig N50 and scaffold N50 are 13.30 Mb and 27.55 Mb, respectively. The genome is predicted to contain 22,109 protein-coding genes, with 96.1% having functional annotations. Repeat elements account for approximately 35.79% of the genomic landscape. The completeness of darkbarbel catfish genome assembly is highlighted by a BUSCO score of 99.07%. This high-quality genome assembly provides a critical resource for future hybrid catfish breeding, comparative genomics, and evolutionary studies in catfish and other related species.
MicroCT data provide evidence correcting the previous misidentification of an Eocene amber beetle (Coleoptera, Cicindelidae) as an extant species
Authors: Schmidt Joachim , Scholz Stephan , Wiesner Jürgen , Will Kipling 
Published: September 2023

AbstractThe fossil record suggests some insect species have a marked longevity. The oldest fossils purported to represent extant insect species are from the Oligocene and Eocene. One of the most cited fossils is the extant tiger beetle Tetracha carolina (Coleoptera: Cicindelidae) that was identified over a century ago by Walther Horn in Eocene Baltic amber. We examined this and compared it to the previously described cincindelid Baltic amber fossil Palaeoiresina cassolai using X-ray microscopy and 3D imaging techniques. We conclude that Horn’s fossil tiger beetle specimen is conspecific with the Eocene P. cassolai and is a member of an extinct stem group lineage of Cicindelidae. Based on a review of all the tiger beetle fossils described from Cretaceous and Paleogene deposits, we found that the assignment of these fossil species to extant lineages is not supported. There are currently no synapomorphies known from fossils that can provide evidence for Cretaceous Manticorni or Megacephalini nor is there evidence for Eocene Iresina. We provide evidence that rejects the idea of a recent beetle species persisting since the Eocene period, which is crucial for using the currently known fossil Cicindelidae species to calibrate divergence dating of beetle phylogenies.