bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear actin structure regulates chromatin accessibility
Authors: Sen Buer , Xie Zhihui , Thomas Michelle D. , Pattenden Samantha G. , Howard Sean , McGrath Cody , Styner Maya , Uzer Gunes , Furey Terrence S. , Rubin Janet 
Published: May 2024

AbstractPolymerized β-actin may provide a structural basis for chromatin accessibility and actin transport into the nucleus can guide mesenchymal stem cell (MSC) differentiation. Using MSC, we show that using CK666 to inhibit Arp2/3 directed secondary actin branching results in decreased nuclear actin structure, and significantly alters chromatin access measured with ATACseq at 24 h. The ATAC-seq results due to CK666 are distinct from those caused by cytochalasin D (CytoD), which enhances nuclear actin structure. In addition, nuclear visualization shows Arp2/3 inhibition decreases pericentric H3K9me3 marks. CytoD, alternatively, induces redistribution of H3K27me3 marks centrally. Such alterations in chromatin landscape are consistent with differential gene expression associated with distinctive differentiation patterns. Further, knockdown of the non-enzymatic monomeric actin binding protein, Arp4, leads to extensive chromatin unpacking, but only a modest increase in transcription, indicating an active role for actin-Arp4 in transcription. These data indicate that dynamic actin remodeling can regulate chromatin interactions.
Late-stage benzenoid-to-troponoid skeletal modification of the cephalotanes exemplified by the total synthesis of harringtonolide
Authors: Wiesler Stefan , Sennari Goh , Popescu Mihai V. , Gardner Kristen E. , Aida Kazuhiro , Paton Robert S. , Sarpong Richmond 
Published: May 2024

AbstractSkeletal modifications enable elegant and rapid access to various derivatives of a compound that would otherwise be difficult to prepare. They are therefore a powerful tool, especially in the synthesis of natural products or drug discovery, to explore different natural products or to improve the properties of a drug candidate starting from a common intermediate. Inspired by the biosynthesis of the cephalotane natural products, we report here a single-atom insertion into the framework of the benzenoid subfamily, providing access to the troponoid congeners — representing the reverse of the proposed biosynthesis (i.e., a contra-biosynthesis approach). Computational evaluation of our designed transformation prompted us to investigate a Büchner–Curtius–Schlotterbeck reaction of a p-quinol methylether, which ultimately results in the synthesis of harringtonolide in two steps from cephanolide A, which we had previously prepared. Additional computational studies reveal that unconventional selectivity outcomes are driven by the choice of a Lewis acid and the nucleophile, which should inform further developments of these types of reactions.
Structure and genome editing of type I-B CRISPR-Cas
Authors: Lu Meiling , Yu Chenlin , Zhang Yuwen , Ju Wenjun , Ye Zhi , Hua Chenyang , Mao Jinze , Hu Chunyi , Yang Zhenhuang , Xiao Yibei 
Published: May 2024

AbstractType I CRISPR-Cas systems employ multi-subunit effector Cascade and helicase-nuclease Cas3 to target and degrade foreign nucleic acids, representing the most abundant RNA-guided adaptive immune systems in prokaryotes. Their ability to cause long fragment deletions have led to increasing interests in eukaryotic genome editing. While the Cascade structures of all other six type I systems have been determined, the structure of the most evolutionarily conserved type I-B Cascade is still missing. Here, we present two cryo-EM structures of the Synechocystis sp. PCC 6714 (Syn) type I-B Cascade, revealing the molecular mechanisms that underlie RNA-directed Cascade assembly, target DNA recognition, and local conformational changes of the effector complex upon R-loop formation. Remarkably, a loop of Cas5 directly intercalated into the major groove of the PAM and facilitated PAM recognition. We further characterized the genome editing profiles of this I-B Cascade-Cas3 in human CD3+ T cells using mRNA-mediated delivery, which led to unidirectional 4.5 kb deletion in TRAC locus and achieved an editing efficiency up to 41.2%. Our study provides the structural basis for understanding target DNA recognition by type I-B Cascade and lays foundation for harnessing this system for long range genome editing in human T cells.
Current advances and future trends of hormesis in disease
Authors: Wan Yantong , Liu Jinxi , Mai Yiyin , Hong Yinghao , Jia Zixuan , Tian Guijie , Liu Yunzhuo , Liang Huaping , Liu Jinghua 
Published: May 2024

AbstractHormesis, an adaptive response, occurs when exposure to low doses of a stressor potentially induces a stimulatory effect, while higher doses may inhibit it. This phenomenon is widely observed across various organisms and stressors, significantly advancing our understanding and inspiring further exploration of the beneficial effects of toxins at doses both below and beyond traditional thresholds. This has profound implications for promoting biological regulation at the cellular level and enhancing adaptability throughout the biosphere. Therefore, conducting bibliometric analysis in this field is crucial for accurately analyzing and summarizing its current research status. The results of the bibliometric analysis reveal a steady increase in the number of publications in this field over the years. The United States emerges as the leading country in both publication and citation numbers, with the journal Dose–Response publishing the highest number of papers in this area. Calabrese E.J. is a prominent person with significant contributions and influence among authors. Through keyword co-occurrence and trend analysis, current hotspots in this field are identified, primarily focusing on the relationship between hormesis, oxidative stress, and aging. Analysis of highly cited references predicts that future research trends may center around the relationship between hormesis and stress at different doses, as well as exploring the mechanisms and applications of hormesis. In conclusion, this review aims to visually represent hormesis-related research through bibliometric methods, uncovering emerging patterns and areas of focus within the field. It provides a summary of the current research status and forecasts trends in hormesis-related research.
Assessing the suitability of desalination techniques for hydraulic barriers
Authors: Rosentreter Hanna , Walther Marc , Lerch André 
Published: May 2024

AbstractSeawater intrusion is a worldwide increasing challenge, which lowers the freshwater availability by salination of fresh groundwater resources in coastal areas. The abstraction-desalination-recharge (ADR) methodology can combat seawater intrusion, whereby desalination is hereby the key factor for the overall efficiency of aquifer remediation. Which desalination technique is suitable within ADR depends on several factors and was not discussed before. We use a multi-criteria decision analysis and cost analysis to compare nanofiltration, reverse osmosis, electrodialysis, and (membrane) capacitive deionization and show for three case scenarios which desalination technique is most suitable within ADR. Overall, electrodialysis, nanofiltration, and reverse osmosis have shown the best utility value for saline groundwater salinity of 1–10 g L−1, whereby electrodialysis is more suitable for lower salinities. The lowest desalination costs are calculated for nanofiltration and reverse osmosis with 0.3–0.6 € m−3 depending on specific energy costs. Even capacitive deionisation can be a suitable alternative for low, slightly saline groundwater (1 g L−1) if the technology readiness level and a lifetime of electrodes increase and material costs decrease. These new insights provide a data analysis, costs, and decision support for desalination which are needed for the holistic approach to counteract seawater intrusion.
Response of tropical forest productivity to seasonal drought mediated by potassium and phosphorus availability
Authors: Manu Raphael , Iddris Najeeb Al-Amin , Corre Marife D. , Aleeje Alfred , Mwanjalolo Majaliwa J. G. , van Straaten Oliver , Veldkamp Edzo 
Published: May 2024

AbstractTropical forest productivity is increasingly reported to be nutrient limited, which may affect its response to seasonal droughts. Yet experimental evidence on nutrient limitation from Afrotropical forests remains rare. We conducted an ecosystem-scale, full factorial nitrogen (N)–phosphorus (P)–potassium (K) addition experiment in a moist forest in Uganda to investigate nutrient controls on fine litter production and foliar chemistry. The eight factorial treatments were replicated four times in 32 plots of 40 × 40 m each. During the three-year nutrient additions, we found K and P limitations on leaf litter production, exhibiting strong links to ecosystem responses to seasonal drought. Specifically, leaf litterfall consistently decreased in dry seasons with K additions, whereas P additions caused a reduction only during prolonged drought in the first year. Leaf litterfall was not significantly affected by N additions. Furthermore, K additions delayed the timing of leaf litterfall peak, underscoring the crucial role of K in regulating stomatal aperture and signalling during water-stress conditions and suggesting a prolonged leaf lifespan. Foliar N increased with N and P additions whereas K was the most resorbed nutrient. We conclude that the productivity and resilience of tropical forests, particularly under drier conditions, may depend on terrestrial K and P availability.
Arresting failure propagation in buildings through collapse isolation
Authors: Makoond Nirvan , Setiawan Andri , Buitrago Manuel , Adam Jose M. 
Published: May 2024

AbstractSeveral catastrophic building collapses1–5 occur because of the propagation of local-initial failures6,7. Current design methods attempt to completely prevent collapse after initial failures by improving connectivity between building components. These measures ensure that the loads supported by the failed components are redistributed to the rest of the structural system8,9. However, increased connectivity can contribute to collapsing elements pulling down parts of a building that would otherwise be unaffected10. This risk is particularly important when large initial failures occur, as tends to be the case in the most disastrous collapses6. Here we present an original design approach to arrest collapse propagation after major initial failures. When a collapse initiates, the approach ensures that specific elements fail before the failure of the most critical components for global stability. The structural system thus separates into different parts and isolates collapse when its propagation would otherwise be inevitable. The effectiveness of the approach is proved through unique experimental tests on a purposely built full-scale building. We also demonstrate that large initial failures would lead to total collapse of the test building if increased connectivity was implemented as recommended by present guidelines. Our proposed approach enables incorporating a last line of defence for more resilient buildings.
GLP-1-directed NMDA receptor antagonism for obesity treatment
Authors: Petersen Jonas , Ludwig Mette Q. , Juozaityte Vaida , Ranea-Robles Pablo , Svendsen Charlotte , Hwang Eunsang , Kristensen Amalie W. , Fadahunsi Nicole , Lund Jens , Breum Alberte W. , Mathiesen Cecilie V. , Sachs Luisa , Moreno-Justicia Roger , Rohlfs Rebecca , Ford James C. , Douros Jonathan D. , Finan Brian , Portillo Bryan , Grose Kyle , Petersen Jacob E. , Trauelsen Mette , Feuchtinger Annette , DiMarchi Richard D. , Schwartz Thue W. , Deshmukh Atul S. , Thomsen Morten B. , Kohlmeier Kristi A. , Williams Kevin W. , Pers Tune H. , Frølund Bente , Strømgaard Kristian , Klein Anders B. , Clemmensen Christoffer 
Published: May 2024

AbstractThe N-methyl-d-aspartate (NMDA) receptor is a glutamate-activated cation channel that is critical to many processes in the brain. Genome-wide association studies suggest that glutamatergic neurotransmission and NMDA receptor-mediated synaptic plasticity are important for body weight homeostasis1. Here we report the engineering and preclinical development of a bimodal molecule that integrates NMDA receptor antagonism with glucagon-like peptide-1 (GLP-1) receptor agonism to effectively reverse obesity, hyperglycaemia and dyslipidaemia in rodent models of metabolic disease. GLP-1-directed delivery of the NMDA receptor antagonist MK-801 affects neuroplasticity in the hypothalamus and brainstem. Importantly, targeting of MK-801 to GLP-1 receptor-expressing brain regions circumvents adverse physiological and behavioural effects associated with MK-801 monotherapy. In summary, our approach demonstrates the feasibility of using peptide-mediated targeting to achieve cell-specific ionotropic receptor modulation and highlights the therapeutic potential of unimolecular mixed GLP-1 receptor agonism and NMDA receptor antagonism for safe and effective obesity treatment.
Wavefunction matching for solving quantum many-body problems
Authors: Elhatisari Serdar , Bovermann Lukas , Ma Yuan-Zhuo , Epelbaum Evgeny , Frame Dillon , Hildenbrand Fabian , Kim Myungkuk , Kim Youngman , Krebs Hermann , Lähde Timo A. , Lee Dean , Li Ning , Lu Bing-Nan , Meißner Ulf-G. , Rupak Gautam , Shen Shihang , Song Young-Ho , Stellin Gianluca 
Published: May 2024

AbstractAb initio calculations have an essential role in our fundamental understanding of quantum many-body systems across many subfields, from strongly correlated fermions1–3to quantum chemistry4–6and from atomic and molecular systems7–9to nuclear physics10–14. One of the primary challenges is to perform accurate calculations for systems where the interactions may be complicated and difficult for the chosen computational method to handle. Here we address the problem by introducing an approach called wavefunction matching. Wavefunction matching transforms the interaction between particles so that the wavefunctions up to some finite range match that of an easily computable interaction. This allows for calculations of systems that would otherwise be impossible owing to problems such as Monte Carlo sign cancellations. We apply the method to lattice Monte Carlo simulations15,16of light nuclei, medium-mass nuclei, neutron matter and nuclear matter. We use high-fidelity chiral effective field theory interactions17,18and find good agreement with empirical data. These results are accompanied by insights on the nuclear interactions that may help to resolve long-standing challenges in accurately reproducing nuclear binding energies, charge radii and nuclear-matter saturation in ab initio calculations19,20.
Comparing built-up area datasets to assess urban exposure to coastal hazards in Europe
Authors: Bonatz Hedda , Reimann Lena , Vafeidis Athanasios T. 
Published: May 2024

AbstractInformation on urban land use, beyond the urban-rural dichotomy, can improve the assessment of potential impacts of coastal hazards by refining estimates of damages and supporting adaptation planning. However, the lack of a consistent definition of “urban” in previous studies has led to exposure estimates that vary considerably. Here, we explore the sensitivity of exposed population and built-up area in four settlement types, defined by four different built-up area datasets. We find large differences in the exposed population of up to 65% (127 million people) in the “Urban” class. The exposure estimates are highly sensitive to the density thresholds used to distinguish the settlement types, with a difference in exposed urban population of up to 53.5 million people when the threshold varies by 10%. We attribute the high sensitivity of the exposure estimates to the varying definitions of built-up area of the underlying datasets. We argue that the definition of urban land is crucial for coastal impact assessments and make recommendations for the use of the analyzed datasets.
Proteomics profiling of the honeybee parasite Tropilaelaps mercedesae across post-embryonic development
Authors: Wei Qiaohong , Wu Jiangli , Liu Fengying , Sun Jiajing , Kang Weipeng , Zhao Meijiao , Wang Feng , Zhang Chenhuan , Xu Shufa , Han Bin 
Published: May 2024

AbstractTropilaelaps mercedesae, an ectoparasitic mite of honeybees, is currently a severe health risk to Apis mellifera colonies in Asia and a potential threat to the global apiculture industry. However, our understanding of the physiological and developmental regulation of this pest remains significantly insufficient. Using ultra-high resolution mass spectrometry, we provide the first comprehensive proteomic profile of T. mercedesae spanning its entire post-embryonic ontogeny, including protonymphs, deutonymphs, mature adults, and reproductive mites. Consequently, a total of 4,422 T. mercedesae proteins were identified, of which 2,189 proteins were significantly differentially expressed (FDR < 0.05) throughout development and maturation. Our proteomic data provide an important resource for understanding the biology of T. mercedesae, and will contribute to further research and effective control of this devastating honeybee pest.
POSoligo software for in vitro gene synthesis
Authors: Tong Yingying , Sun Jie , Chen Yang , Yi Changhua , Wang Hua , Li Caixin , Dai Nana , Yang Guanghua 
Published: May 2024

AbstractOligonucleotide synthesis is vital for molecular experiments. Bioinformatics has been employed to create various algorithmic tools for the in vitro synthesis of nucleotides. The main approach to synthesizing long-chain DNA molecules involves linking short-chain oligonucleotides through ligase chain reaction (LCR) and polymerase chain reaction (PCR). Short-chain DNA molecules have low mutation rates, while LCR requires complementary interfaces at both ends of the two nucleic acid molecules or may alter the conformation of the nucleotide chain, leading to termination of amplification. Therefore, molecular melting temperature, length, and specificity must be considered during experimental design. POSoligo is a specialized offline tool for nucleotide fragment synthesis. It optimizes the oligonucleotide length and specificity based on input single-stranded DNA, producing multiple contiguous long strands (COS) and short patch strands (POS) with complementary ends. This process ensures free 5′- and 3′-ends during oligonucleotide synthesis, preventing secondary structure formation and ensuring specific binding between COS and POS without relying on stabilizing the complementary strands based on Tm values. POSoligo was used to synthesize the linear RBD sequence of SARS-CoV-2 using only one DNA strand, several POSs for LCR ligation, and two pairs of primers for PCR amplification in a time- and cost-effective manner.
Advancing molecular modeling and reverse vaccinology in broad-spectrum yellow fever virus vaccine development
Authors: da Silva Ohana Leticia Tavares , da Silva Maria Karolaynne , Rodrigues-Neto Joao Firmino , Santos Lima Joao Paulo Matos , Manzoni Vinicius , Akash Shopnil , Fulco Umberto Laino , Bourhia Mohammed , Dawoud Turki M. , Nafidi Hiba-Allah , Sitotaw Baye , Akter Shahina , Oliveira Jonas Ivan Nobre 
Published: May 2024

AbstractYellow fever outbreaks are prevalent, particularly in endemic regions. Given the lack of an established treatment for this disease, significant attention has been directed toward managing this arbovirus. In response, we developed a multiepitope vaccine designed to elicit an immune response, utilizing advanced immunoinformatic and molecular modeling techniques. To achieve this, we predicted B- and T-cell epitopes using the sequences from all structural (E, prM, and C) and nonstructural proteins of 196 YFV strains. Through comprehensive analysis, we identified 10 cytotoxic T-lymphocyte (CTL) and 5T-helper (Th) epitopes that exhibited overlap with B-lymphocyte epitopes. These epitopes were further evaluated for their affinity to a wide range of human leukocyte antigen system alleles and were rigorously tested for antigenicity, immunogenicity, allergenicity, toxicity, and conservation. These epitopes were linked to an adjuvant ($$\beta$$
β
-defensin) and to each other using ligands, resulting in a vaccine sequence with appropriate physicochemical properties. The 3D structure of this sequence was created, improved, and quality checked; then it was anchored to the Toll-like receptor. Molecular Dynamics and Quantum Mechanics/Molecular Mechanics simulations were employed to enhance the accuracy of docking calculations, with the QM portion of the simulations carried out utilizing the density functional theory formalism. Moreover, the inoculation model was able to provide an optimal codon sequence that was inserted into the pET-28a( +) vector for in silico cloning and could even stimulate highly relevant humoral and cellular immunological responses. Overall, these results suggest that the designed multi-epitope vaccine can serve as prophylaxis against the yellow fever virus.
Low-adhesion culture selection for human iPS cell-derived cardiomyocytes
Authors: Kikuchi Tetsutaro , Matsuura Katsuhisa , Shimizu Tatsuya 
Published: May 2024

AbstractDespite progress in generating cardiomyocytes from pluripotent stem cells, these populations often include non-contractile cells, necessitating cardiomyocyte selection for experimental purpose. This study explores a novel cardiomyocyte enrichment mechanism: low-adhesion culture selection. The cardiac cells derived from human induced pluripotent stem cells were subjected to a coating-free low-adhesion culture using bovine serum albumin and high molecular weight dextran sulfate. This approach effectively increased the population of cardiac troponin T-positive cardiomyocytes. Similar results were obtained with commercially available low-adhesion culture dishes. Subsequently, we accessed the practicality of selection of cardiomyocytes using this phenomenon by comparing it with established methods such as glucose-free culture and selection based on puromycin resistance genes. The cardiomyocytes enriched through low-adhesion culture selection maintained autonomous pulsation and responsiveness to beta-stimuli. Moreover, no significant differences were observed in the expression of genes related to subtype commitment and maturation when compared to other selection methods. In conclusion, cardiomyocytes derived from pluripotent stem cells were more low-adhesion culture resistant than their accompanying non-contractile cells, and low-adhesion culture is an alternative method for selection of pluripotent stem cell-derived cardiomyocytes.
Prediction of treatment response after stereotactic radiosurgery of brain metastasis using deep learning and radiomics on longitudinal MRI data
Authors: Cho Se Jin , Cho Wonwoo , Choi Dongmin , Sim Gyuhyeon , Jeong So Yeong , Baik Sung Hyun , Bae Yun Jung , Choi Byung Se , Kim Jae Hyoung , Yoo Sooyoung , Han Jung Ho , Kim Chae-Yong , Choo Jaegul , Sunwoo Leonard 
Published: May 2024

AbstractWe developed artificial intelligence models to predict the brain metastasis (BM) treatment response after stereotactic radiosurgery (SRS) using longitudinal magnetic resonance imaging (MRI) data and evaluated prediction accuracy changes according to the number of sequential MRI scans. We included four sequential MRI scans for 194 patients with BM and 369 target lesions for the Developmental dataset. The data were randomly split (8:2 ratio) for training and testing. For external validation, 172 MRI scans from 43 patients with BM and 62 target lesions were additionally enrolled. The maximum axial diameter (Dmax), radiomics, and deep learning (DL) models were generated for comparison. We evaluated the simple convolutional neural network (CNN) model and a gated recurrent unit (Conv-GRU)-based CNN model in the DL arm. The Conv-GRU model performed superior to the simple CNN models. For both datasets, the area under the curve (AUC) was significantly higher for the two-dimensional (2D) Conv-GRU model than for the 3D Conv-GRU, Dmax, and radiomics models. The accuracy of the 2D Conv-GRU model increased with the number of follow-up studies. In conclusion, using longitudinal MRI data, the 2D Conv-GRU model outperformed all other models in predicting the treatment response after SRS of BM.