bluuebunny/crossref_metadata_2025_split huggingface dataset:
iPS cell generation-associated point mutations include many C > T substitutions via different cytosine modification mechanisms
Authors: Araki Ryoko , Suga Tomo , Hoki Yuko , Imadome Kaori , Sunayama Misato , Kamimura Satoshi , Fujita Mayumi , Abe Masumi 
Published: June 2024

AbstractGenomic aberrations are a critical impediment for the safe medical use of iPSCs and their origin and developmental mechanisms remain unknown. Here we find through WGS analysis of human and mouse iPSC lines that genomic mutations are de novo events and that, in addition to unmodified cytosine base prone to deamination, the DNA methylation sequence CpG represents a significant mutation-prone site. CGI and TSS regions show increased mutations in iPSCs and elevated mutations are observed in retrotransposons, especially in the AluY subfamily. Furthermore, increased cytosine to thymine mutations are observed in differentially methylated regions. These results indicate that in addition to deamination of cytosine, demethylation of methylated cytosine, which plays a central role in genome reprogramming, may act mutagenically during iPSC generation.
Non-viral DNA delivery and TALEN editing correct the sickle cell mutation in hematopoietic stem cells
Authors: Moiani Arianna , Letort Gil , Lizot Sabrina , Chalumeau Anne , Foray Chloe , Felix Tristan , Le Clerre Diane , Temburni-Blake Sonal , Hong Patrick , Leduc Sophie , Pinard Noemie , Marechal Alan , Seclen Eduardo , Boyne Alex , Mayer Louisa , Hong Robert , Pulicani Sylvain , Galetto Roman , Gouble Agnès , Cavazzana Marina , Juillerat Alexandre , Miccio Annarita , Duclert Aymeric , Duchateau Philippe , Valton Julien 
Published: June 2024

AbstractSickle cell disease is a devastating blood disorder that originates from a single point mutation in the HBB gene coding for hemoglobin. Here, we develop a GMP-compatible TALEN-mediated gene editing process enabling efficient HBB correction via a DNA repair template while minimizing risks associated with HBB inactivation. Comparing viral versus non-viral DNA repair template delivery in hematopoietic stem and progenitor cells in vitro, both strategies achieve comparable HBB correction and result in over 50% expression of normal adult hemoglobin in red blood cells without inducing β-thalassemic phenotype. In an immunodeficient female mouse model, transplanted cells edited with the non-viral strategy exhibit higher engraftment and gene correction levels compared to those edited with the viral strategy. Transcriptomic analysis reveals that non-viral DNA repair template delivery mitigates P53-mediated toxicity and preserves high levels of long-term hematopoietic stem cells. This work paves the way for TALEN-based autologous gene therapy for sickle cell disease.
Acetylation of histones and non-histone proteins is not a mere consequence of ongoing transcription
Authors: Liebner Tim , Kilic Sinan , Walter Jonas , Aibara Hitoshi , Narita Takeo , Choudhary Chunaram 
Published: June 2024

AbstractIn all eukaryotes, acetylation of histone lysine residues correlates with transcription activation. Whether histone acetylation is a cause or consequence of transcription is debated. One model suggests that transcription promotes the recruitment and/or activation of acetyltransferases, and histone acetylation occurs as a consequence of ongoing transcription. However, the extent to which transcription shapes the global protein acetylation landscapes is not known. Here, we show that global protein acetylation remains virtually unaltered after acute transcription inhibition. Transcription inhibition ablates the co-transcriptionally occurring ubiquitylation of H2BK120 but does not reduce histone acetylation. The combined inhibition of transcription and CBP/p300 further demonstrates that acetyltransferases remain active and continue to acetylate histones independently of transcription. Together, these results show that histone acetylation is not a mere consequence of transcription; acetyltransferase recruitment and activation are uncoupled from the act of transcription, and histone and non-histone protein acetylation are sustained in the absence of ongoing transcription.
t-SMILES: a fragment-based molecular representation framework for de novo ligand design
Authors: Wu Juan-Ni , Wang Tong , Chen Yue , Tang Li-Juan , Wu Hai-Long , Yu Ru-Qin 
Published: June 2024

AbstractEffective representation of molecules is a crucial factor affecting the performance of artificial intelligence models. This study introduces a flexible, fragment-based, multiscale molecular representation framework called t-SMILES (tree-based SMILES) with three code algorithms: TSSA (t-SMILES with shared atom), TSDY (t-SMILES with dummy atom but without ID) and TSID (t-SMILES with ID and dummy atom). It describes molecules using SMILES-type strings obtained by performing a breadth-first search on a full binary tree formed from a fragmented molecular graph. Systematic evaluations using JTVAE, BRICS, MMPA, and Scaffold show the feasibility of constructing a multi-code molecular description system, where various descriptions complement each other, enhancing the overall performance. In addition, it can avoid overfitting and achieve higher novelty scores while maintaining reasonable similarity on labeled low-resource datasets, regardless of whether the model is original, data-augmented, or pre-trained then fine-tuned. Furthermore, it significantly outperforms classical SMILES, DeepSMILES, SELFIES and baseline models in goal-directed tasks. And it surpasses state-of-the-art fragment, graph and SMILES based approaches on ChEMBL, Zinc, and QM9.
Growth of electroautotrophic microorganisms using hydrovoltaic energy through natural water evaporation
Authors: Ren Guoping , Ye Jie , Hu Qichang , Zhang Dong , Yuan Yong , Zhou Shungui 
Published: June 2024

AbstractIt has been previously shown that devices based on microbial biofilms can generate hydrovoltaic energy from water evaporation. However, the potential of hydrovoltaic energy as an energy source for microbial growth has remained unexplored. Here, we show that the electroautotrophic bacterium Rhodopseudomonas palustris can directly utilize evaporation-induced hydrovoltaic electrons for growth within biofilms through extracellular electron uptake, with a strong reliance on carbon fixation coupled with nitrate reduction. We obtained similar results with two other electroautotrophic bacterial species. Although the energy conversion efficiency for microbial growth based on hydrovoltaic energy is low compared to other processes such as photosynthesis, we hypothesize that hydrovoltaic energy may potentially contribute to microbial survival and growth in energy-limited environments, given the ubiquity of microbial biofilms and water evaporation conditions.
Dispersive Fourier transform based dual-comb ranging
Authors: Chang Bing , Tan Teng , Du Junting , He Xinyue , Liang Yupei , Liu Zihan , Wang Chun , Xia Handing , Wu Zhaohui , Wang Jindong , Wong Kenneth K. Y. , Zhu Tao , Kong Lingjiang , Li Bowen , Rao Yunjiang , Yao Baicheng 
Published: June 2024

AbstractLaser-based light detection and ranging (LIDAR) offers a powerful tool to real-timely map spatial information with exceptional accuracy and owns various applications ranging from industrial manufacturing, and remote sensing, to airborne and in-vehicle missions. Over the past two decades, the rapid advancements of optical frequency combs have ushered in a new era for LIDAR, promoting measurement precision to quantum noise limited level. For comb LIDAR systems, to further improve the comprehensive performances and reconcile inherent conflicts between speed, accuracy, and ambiguity range, innovative demodulation strategies become crucial. Here we report a dispersive Fourier transform (DFT) based LIDAR method utilizing phase-locked Vernier dual soliton laser combs. We demonstrate that after in-line pulse stretching, the delay of the flying pulses can be identified via the DFT-based spectral interferometry instead of temporal interferometry or pulse reconstruction. This enables absolute distance measurements with precision starting from 262 nm in single shot, to 2.8 nm after averaging 1.5 ms, in a non-ambiguity range over 1.7 km. Furthermore, our DFT-based LIDAR method distinctly demonstrates an ability to completely eliminate dead zones. Such an integration of frequency-resolved ultrafast analysis and dual-comb ranging technology may pave a way for the design of future LIDAR systems.
Viviparity imparts a macroevolutionary signature of ecological opportunity in the body size of female Liolaemus lizards
Authors: Domínguez-Guerrero Saúl F. , Esquerré Damien , Burress Edward D. , Maciel-Mata Carlos A. , Alencar Laura R. V. , Muñoz Martha M. 
Published: June 2024

AbstractViviparity evolved ~115 times across squamate reptiles, facilitating the colonization of cold habitats, where oviparous species are scarce or absent. Whether the ecological opportunity furnished by such colonization reconfigures phenotypic diversity and accelerates evolution is unclear. We investigated the association between viviparity and patterns and rates of body size evolution in female Liolaemus lizards, the most species-rich tetrapod genus from temperate regions. Here, we discover that viviparous species evolve ~20% larger optimal body sizes than their oviparous relatives, but exhibit similar rates of body size evolution. Through a causal modeling approach, we find that viviparity indirectly influences body size evolution through shifts in thermal environment. Accordingly, the colonization of cold habitats favors larger body sizes in viviparous species, reconfiguring body size diversity in Liolaemus. The catalyzing influence of viviparity on phenotypic evolution arises because it unlocks access to otherwise inaccessible sources of ecological opportunity, an outcome potentially repeated across the tree of life.
Bioreactor development for skeletal muscle hypertrophy and atrophy by manipulating uniaxial cyclic strain: proof of concept
Authors: Kamal Khaled Y. , Othman Mariam Atef , Kim Joo-Hyun , Lawler John M. 
Published: June 2024

AbstractSkeletal muscles overcome terrestrial, gravitational loading by producing tensile forces that produce movement through joint rotation. Conversely, the microgravity of spaceflight reduces tensile loads in working skeletal muscles, causing an adaptive muscle atrophy. Unfortunately, the design of stable, physiological bioreactors to model skeletal muscle tensile loading during spaceflight experiments remains challenging. Here, we tested a bioreactor that uses initiation and cessation of cyclic, tensile strain to induce hypertrophy and atrophy, respectively, in murine lineage (C2C12) skeletal muscle myotubes. Uniaxial cyclic stretch of myotubes was conducted using a StrexCell® (STB-1400) stepper motor system (0.75 Hz, 12% strain, 60 min day^-1). Myotube groups were assigned as follows: (a) quiescent over 2- or (b) 5-day (no stretch), (c) experienced 2-days (2dHY) or (d) 5-days (5dHY) of cyclic stretch, or (e) 2-days of cyclic stretch followed by a 3-day cessation of stretch (3dAT). Using ß-sarcoglycan as a sarcolemmal marker, mean myotube diameter increased significantly following 2dAT (51%) and 5dAT (94%) vs. matched controls. The hypertrophic, anabolic markers talin and Akt phosphorylation (Thr308) were elevated with 2dHY but not in 3dAT myotubes. Inflammatory, catabolic markers IL-1ß, IL6, and NF-kappaB p65 subunit were significantly higher in the 3dAT group vs. all other groups. The ratio of phosphorylated FoxO3a/total FoxO3a was significantly lower in 3dAT than in the 2dHY group, consistent with elevated catabolic signaling during unloading. In summary, we demonstrated proof-of-concept for a spaceflight research bioreactor, using uniaxial cyclic stretch to produce myotube hypertrophy with increased tensile loading, and myotube atrophy with subsequent cessation of stretch.
Sequential closed-loop Bayesian optimization as a guide for organic molecular metallophotocatalyst formulation discovery
Authors: Li Xiaobo , Che Yu , Chen Linjiang , Liu Tao , Wang Kewei , Liu Lunjie , Yang Haofan , Pyzer-Knapp Edward O. , Cooper Andrew I. 
Published: June 2024

AbstractConjugated organic photoredox catalysts (OPCs) can promote a wide range of chemical transformations. It is challenging to predict the catalytic activities of OPCs from first principles, either by expert knowledge or by using a priori calculations, as catalyst activity depends on a complex range of interrelated properties. Organic photocatalysts and other catalyst systems have often been discovered by a mixture of design and trial and error. Here we report a two-step data-driven approach to the targeted synthesis of OPCs and the subsequent reaction optimization for metallophotocatalysis, demonstrated for decarboxylative sp3–sp2 cross-coupling of amino acids with aryl halides. Our approach uses a Bayesian optimization strategy coupled with encoding of key physical properties using molecular descriptors to identify promising OPCs from a virtual library of 560 candidate molecules. This led to OPC formulations that are competitive with iridium catalysts by exploring just 2.4% of the available catalyst formulation space (107 of 4,500 possible reaction conditions).
A decrease in radiative forcing and equivalent effective chlorine from hydrochlorofluorocarbons
Authors: Western Luke M. , Daniel John S. , Vollmer Martin K. , Clingan Scott , Crotwell Molly , Fraser Paul J. , Ganesan Anita L. , Hall Brad , Harth Christina M. , Krummel Paul B. , Mühle Jens , O’Doherty Simon , Salameh Peter K. , Stanley Kieran M. , Reimann Stefan , Vimont Isaac , Young Dickon , Rigby Matt , Weiss Ray F. , Prinn Ronald G. , Montzka Stephen A. 
Published: June 2024

AbstractThe Montreal Protocol and its successive amendments have been successful in curbing emissions of ozone-depleting substances and potent greenhouse gases via production/consumption controls. Here we show that the radiative forcing and equivalent effective chlorine from hydrochlorofluorocarbons has decreased from 61.75 mW m−2 and 321.69 ppt, respectively, since 2021, 5 years before the most recent projected decrease. This important milestone demonstrates the benefits of the Protocol for mitigating climate change and stratospheric ozone layer loss.
Decision uncertainty as a context for motor memory
Authors: Ogasa Kisho , Yokoi Atsushi , Okazawa Gouki , Nishigaki Morimichi , Hirashima Masaya , Hagura Nobuhiro 
Published: June 2024

AbstractThe current view of perceptual decision-making suggests that once a decision is made, only a single motor programme associated with the decision is carried out, irrespective of the uncertainty involved in decision making. In contrast, we show that multiple motor programmes can be acquired on the basis of the preceding uncertainty of the decision, indicating that decision uncertainty functions as a contextual cue for motor memory. The actions learned after making certain (uncertain) decisions are only partially transferred to uncertain (certain) decisions. Participants were able to form distinct motor memories for the same movement on the basis of the preceding decision uncertainty. Crucially, this contextual effect generalizes to novel stimuli with matched uncertainty levels, demonstrating that decision uncertainty is itself a contextual cue. These findings broaden the understanding of contextual inference in motor memory, emphasizing that it extends beyond direct motor control cues to encompass the decision-making process.
An immune-related eleven-RNA signature-drived risk score model for prognosis of osteosarcoma metastasis
Authors: Teng Jia-Song , Wang Yang 
Published: June 2024

AbstractThis study aimed to determine an immune-related RNA signature as a prognostic marker, in this study, we developed a risk score model for predicting the prognosis of osteosarcoma metastasis. We first downloaded the clinical information and expression data of osteosarcoma samples from the UCSC Xena and GEO databases, of which the former was the training set and the latter was the validation set. Immune infiltration was assessed using the ssGSEA and ESTIMATE algorithms, and the osteosarcoma samples were divided into the Immunity_L and Immunity_H groups. Then, eleven RNAs were identified as the optimal prognostic RNA signatures using LASSO Cox regression analysis for establishing a risk score (RS) model. Kaplan–Meier approach indicated the high-risk group exhibited a shorter survival. Furthermore, we analyzed the tumor metastasis, age, and RS model status were determined to be independent clinical prognostic factors using Cox regression analysis. Decision curve analysis (DCA) indicated that the prognostic factor + RS model had the best net benefit. Finally, nine tumor-infiltrating immune cells (TIICs) showed significant differences in abundance between high- and low-risk groups via CIBERSORT deconvolution algorithm. In conclusion, the immune-related eleven-RNA signature be could served as a potential prognostic biomarker for osteosarcoma metastasis.
Aging and putative frailty biomarkers are altered by spaceflight
Authors: Camera Andrea , Tabetah Marshall , Castañeda Veronica , Kim JangKeun , Galsinh Aman Singh , Haro-Vinueza Alissen , Salinas Ivonne , Seylani Allen , Arif Shehbeel , Das Saswati , Mori Marcelo A. , Carano Anthony , de Oliveira Lorraine Christine , Muratani Masafumi , Barker Richard , Zaksas Victoria , Goel Chirag , Dimokidis Eleni , Taylor Deanne M. , Jeong Jisu , Overbey Eliah , Meydan Cem , Porterfield D. Marshall , Díaz Juan Esteban , Caicedo Andrés , Schisler Jonathan C. , Laiakis Evagelia C. , Mason Christopher E. , Kim Man S. , Karouia Fathi , Szewczyk Nathaniel J. , Beheshti Afshin 
Published: June 2024

AbstractHuman space exploration poses inherent risks to astronauts’ health, leading to molecular changes that can significantly impact their well-being. These alterations encompass genomic instability, mitochondrial dysfunction, increased inflammation, homeostatic dysregulation, and various epigenomic changes. Remarkably, these changes bear similarities to those observed during the aging process on Earth. However, our understanding of the connection between these molecular shifts and disease development in space remains limited. Frailty syndrome, a clinical syndrome associated with biological aging, has not been comprehensively investigated during spaceflight. To bridge this knowledge gap, we leveraged murine data obtained from NASA’s GeneLab, along with astronaut data gathered from the JAXA and Inspiration4 missions. Our objective was to assess the presence of biological markers and pathways related to frailty, aging, and sarcopenia within the spaceflight context. Through our analysis, we identified notable changes in gene expression patterns that may be indicative of the development of a frailty-like condition during space missions. These findings suggest that the parallels between spaceflight and the aging process may extend to encompass frailty as well. Consequently, further investigations exploring the utility of a frailty index in monitoring astronaut health appear to be warranted.
Learning cooking algorithm for solving global optimization problems
Authors: Gopi S. , Mohapatra Prabhujit 
Published: June 2024

AbstractIn recent years, many researchers have made a continuous effort to develop new and efficient meta-heuristic algorithms to address complex problems. Hence, in this study, a novel human-based meta-heuristic algorithm, namely, the learning cooking algorithm (LCA), is proposed that mimics the cooking learning activity of humans in order to solve challenging problems. The LCA strategy is primarily motivated by observing how mothers and children prepare food. The fundamental idea of the LCA strategy is mathematically designed in two phases: (i) children learn from their mothers and (ii) children and mothers learn from a chef. The performance of the proposed LCA algorithm is evaluated on 51 different benchmark functions (which includes the first 23 functions of the CEC 2005 benchmark functions) and the CEC 2019 benchmark functions compared with state-of-the-art meta-heuristic algorithms. The simulation results and statistical analysis such as the t-test, Wilcoxon rank-sum test, and Friedman test reveal that LCA may effectively address optimization problems by maintaining a proper balance between exploitation and exploration. Furthermore, the LCA algorithm has been employed to solve seven real-world engineering problems, such as the tension/compression spring design, pressure vessel design problem, welded beam design problem, speed reducer design problem, gear train design problem, three-bar truss design, and cantilever beam problem. The results demonstrate the LCA’s superiority and capability over other algorithms in solving complex optimization problems.
Whole-genome sequencing identifies variants in ANK1, LRRN1, HAS1, and other genes and regulatory regions for stroke in type 1 diabetes
Authors: Antikainen Anni A. , Haukka Jani K. , Kumar Anmol , Syreeni Anna , Hägg-Holmberg Stefanie , Ylinen Anni , Kilpeläinen Elina , Kytölä Anastasia , Palotie Aarno , Putaala Jukka , Thorn Lena M. , Harjutsalo Valma , Groop Per-Henrik , Sandholm Niina ,   the FinnDiane Study Group, Antikainen Anni A. , Haukka Jani K. , Kumar Anmol , Syreeni Anna , Hägg-Holmberg Stefanie , Ylinen Anni , Putaala Jukka , Thorn Lena M. , Harjutsalo Valma , Groop Per-Henrik , Sandholm Niina 
Published: June 2024

AbstractIndividuals with type 1 diabetes (T1D) carry a markedly increased risk of stroke, with distinct clinical and neuroimaging characteristics as compared to those without diabetes. Using whole-exome or whole-genome sequencing of 1,051 individuals with T1D, we aimed to find rare and low-frequency genomic variants associated with stroke in T1D. We analysed the genome comprehensively with single-variant analyses, gene aggregate analyses, and aggregate analyses on genomic windows, enhancers and promoters. In addition, we attempted replication in T1D using a genome-wide association study (N = 3,945) and direct genotyping (N = 3,263), and in the general population from the large-scale population-wide FinnGen project and UK Biobank summary statistics. We identified a rare missense variant on SREBF1 exome-wide significantly associated with stroke (rs114001633, p.Pro227Leu, p-value = 7.30 × 10–8), which replicated for hemorrhagic stroke in T1D. Using gene aggregate analysis, we identified exome-wide significant genes: ANK1 and LRRN1 displayed replication evidence in T1D, and LRRN1, HAS1 and UACA in the general population (UK Biobank). Furthermore, we performed sliding-window analyses and identified 14 genome-wide significant windows for stroke on 4q33-34.1, of which two replicated in T1D, and a suggestive genomic window on LINC01500, which replicated in T1D. Finally, we identified a suggestively stroke-associated TRPM2-AS promoter (p-value = 5.78 × 10–6) with borderline significant replication in T1D, which we validated with an in vitro cell-based assay. Due to the rarity of the identified genetic variants, future replication of the genomic regions represented here is required with sequencing of individuals with T1D. Nevertheless, we here report the first genome-wide analysis on stroke in individuals with diabetes.