bluuebunny/crossref_metadata_2025_split huggingface dataset:
Morphological and microbial diversity of hydromagnesite microbialites in Lake Salda, A Ma8rs Analog Alkaline Lake
Authors: Gunes Yagmur , Sekerci Fatih , Avcı Burak , Ettema Thijs J. G. , Balci Nurgul 
Published: September 2023

AbstractLake Salda, recognized as a terrestrial analog for the paleolake in Jezero Crater on Mars, hosts modern, sub/fossil and fossil hydromagnesite microbialites. A comprehensive study was conducted to reveal the distribution, and morphological-mineralogical, microbial diversity of the microbialites that are currently growing in the shallow (<1 m) and deeper waters (up to 15 m) of the lake. Six major microbialite forming zones were identified (Zone I-VI) comprising previously unknown morphotypes of the microbialites. These newly identified morphologies include; linked columns and microbial pavements, exhibiting distinct surface textures such as bulbous, mini columnar, knobby, cerebroidal and smooth. The shallow microbialites showed well-preserved radially growing stromatolitic layers in cm-scale, producing cauliflower structures while the deeper samples exhibit mm scale layering within the mini columnar structures. 16S rRNA amplicon data reveal that abundance of major bacterial taxa of the thrombolitic microbialites from deeper regions are distinct than those of the shallow-growing microbialites with stromatolitic structures. Cyanobacteria were found to be generally less abundant (0.01% to 2%) in the thrombolitic microbialites compared to the stromatolitic microbialites with smooth surface. The Anaerolineae class of the phylum Chloroflexi was prominently present in the stromatolitic microbialites with smooth surface. Notably, the lake exhibited a high abundance of the genusExiguobacterium, particularly in the deep thrombolitic microbialites (e.g., 93%). Microscopy analysis of the deep microbial mats showed the presence of abundant nano and microcrystalline platy/flakey hydrated Mg carbonate crystals that co- existed with mineralized filaments and spherulitic aggregates within abundant exopolymeric substances (EPSs). Moreover, palygorskite mineral was exclusively identified within the deep microbialites. Co-existence of aragonite and hydromagnesite minerals in particular within the deep microbialites that grow under non-evaporative conditions and the abundant presence of entombed biomass (e.g., filamentous) collectively suggest the potential preservation of biosignatures within the hydrated Mg carbonate build-ups in Lake Salda.
Growth deficiency and enhanced basal Immunity inArabidopsis thalianamutants ofEDM2,EDM3andIBM2are genetically interlinked
Authors: Wang Jianqiang , Eulgem Thomas 
Published: September 2023

AbstractMutants of theArabidopsis thalianagenes,EDM2,EDM3andIBM2are known to show defects in a diverse set of defense and developmental processes. For example, they jointly exhibit enhanced levels of basal defense and stunted growth. Here we show that these two phenotypes are functionally connected by their dependency on the salicylic acid biosynthesis geneSID2and the basal defense regulatory genePAD4. Stunted growth ofedm2,edm3andibm2plants is a consequence of up-regulated basal defense. Constitutively enhanced activity of reactive oxygen species-generating peroxidases, we observed in these mutants, appears also to contribute to both, their enhanced basal defense and their growth retardation phenotypes. Furthermore, we found the histone H3 demethylase geneIBM1, a direct regulatory target of EDM2, EDM3 and IBM2, to be at least partially required for the basal defense and growth-related effects observed in these mutants. We recently reported thatEDM2,EDM3andIBM2coordinate the extent of basal immunity with the timing of the floral transition. Together with these observations, data presented here show that at least some of the diverse phenotypic effects inedm2,edm3andibm2mutants are genetically interlinked and functionally connected.
Structural characterization of two nanobodies targeting the ligand-binding pocket of human Arc
Authors: Muñoz José M. Godoy , Neset Lasse , Markússon Sigurbjörn , Weber Sarah , Krokengen Oda C. , Sutinen Aleksi , Christakou Eleni , Moreno Andrea J. Lopez , Bramham Clive R. , Kursula Petri 
Published: September 2023

AbstractThe activity-regulated cytoskeleton-associated protein (Arc) is a complex regulator of synaptic plasticity in glutamatergic neurons. Understanding its molecular function is key to elucidate the neurobiology of memory and learning, stress regulation, and multiple neurological and psychiatric diseases. The recent development of anti-Arc nanobodies has promoted the characterization of the molecular structure and function of Arc. This study aimed to validate two anti-Arc nanobodies, E5 and H11, as selective modulators of the human Arc N-lobe (Arc-NL), a domain that mediates several molecular functions of Arc through its peptide ligand binding site. The structural characteristics of recombinant Arc-NL-nanobody complexes were solved at atomic resolution using X-ray crystallography. The structures revealed that both anti-Arc nanobodies specifically bind to the multi-peptide binding site of Arc-NL. Isothermal titration calorimetry showed that the Arc-NL-nanobody interactions occur at nanomolar affinity, and that the nanobodies can displace a TARPγ2-derived peptide from the Arc-NL binding site. Thus, both anti-Arc-NL nanobodies can be usedin vitroas competitive inhibitors of endogenous Arc ligands. Differences in the CDR3 loops between the two nanobodies indicate that the spectrum of short linear motifs recognized by the Arc-NL should be expanded. We provide a robust biochemical background to support the use of anti-Arc nanobodies in attempts to target Arc-dependent synaptic plasticity. Function-blocking anti-Arc nanobodies could eventually help unravel the complex neurobiology of synaptic plasticity and help diagnose and treat Arc-associated synaptic disorders.
Retrotransposon-driven environmental regulation ofFLCleads to adaptive response to herbicide
Authors: Raingeval Mathieu , Leduque Basile , Baduel Pierre , Edera Alejandro , Roux Fabrice , Colot Vincent , Quadrana Leandro 
Published: September 2023

AbstractThe mobilization of retrotransposons yields major-effect mutations. Here, we report an adaptive retrotransposon insertion within the first intron of the Arabidopsis floral-repressor locusFLOWERING LOCUS C (FLC). The insertion-mutation augments the environmental sensitivity ofFLCby affecting the balance between coding and non-coding transcript isoforms in response to environmental threads. We show that this balance is modulated epigenetically by DNA methylation and orchestrated by IBM2, a factor involved in the processing of intronic heterochromatin. The stress-sensitive allele ofFLChas recently spread across populations subjected to recurrent chemical weeding, and we demonstrate that retrotransposon-driven acceleration of life cycle represents a rapid response to herbicide. Our findings illustrate how retrotransposition can create environmentally-sensitive alleles that facilitate adaptation to anthropogenic disturbances of the environment.
Varying the position of phospholipid acyl chain unsaturation modulates hopanoid and sterol ordering
Authors: Nguyen Ha-Ngoc-Anh , Sharp Liam , Lyman Edward , Saenz James P 
Published: September 2023

AbstractThe cell membrane must balance mechanical stability with fluidity to function as both a barrier and an organizational platform. Key to this balance is the thermodynamic ordering of lipids. Most Eukaryotes employ sterols, which are uniquely capable of modulating lipid order to decouple membrane stability from fluidity. Ancient sterol analogues known as hopanoids are found in many bacteria and are proposed as ancestral ordering lipids. The juxtaposition of sterols and hopanoids in extant organisms prompts us to ask why both pathways persist, especially in light of their convergent ability to order lipids. We reveal that both hopanoids and sterols order unsaturated phospholipids differently based on the position of double bonds in the phospholipid’s acyl chain. We find that cholesterol and diplopterol’s methyl group distributions lead to distinct effects on unsaturated lipids. InMesoplasma florum, diplopterol’s constrained ordering capacity reduces membrane resistance to osmotic stress, unlike cholesterol. These findings suggest cholesterol’s broader lipid ordering ability may have facilitated the exploration of a more diverse lipidomic landscape in eukaryotic membranes.
Brain-wide human oscillatory LFP activity during visual working memory
Authors: Singh Balbir , Wang Zhengyang , Madiah Leen M. , Gatti S. Elizabeth , Fulton Jenna N. , Johnson Graham W. , Li Rui , Dawant Benoit M. , Englot Dario J. , Bick Sarah K. , Roberson Shawniqua Williams , Constantinidis Christos 
Published: September 2023

ABSTRACTOscillatory activity is thought to be a marker of cognitive processes, although its role and distribution across the brain during working memory has been a matter of debate. To understand how oscillatory activity differentiates tasks and brain areas in humans, we recorded local field potentials (LFPs) in 12 adults as they performed visual-spatial and shape-matching memory tasks. Tasks were designed to engage working memory processes at a range of delay intervals between stimulus delivery and response initiation. LFPs were recorded using intracranial depth electrodes implanted to localize seizures for management of intractable epilepsy. Task-related LFP power analyses revealed an extensive network of cortical regions that were activated during the presentation of visual stimuli and during their maintenance in working memory, including occipital, parietal, temporal, insular, and prefrontal cortical areas, and subcortical structures including the amygdala and hippocampus. Across most brain areas, the appearance of a stimulus produced broadband power increase, while gamma power was evident during the delay interval of the working memory task. Notable differences between areas included that occipital cortex was characterized by elevated power in the high gamma (100-150 Hz) range during the 500 ms of visual stimulus presentation, which was less pronounced or absent in other areas. A decrease in power centered in beta frequency (16-40 Hz) was also observed after the stimulus presentation, whose magnitude differed across areas. These results reveal the interplay of oscillatory activity across a broad network, and region-specific signatures of oscillatory processes associated with visual working memory.
A Multi-Layered Computational Structural Genomics Approach Enhances Domain-Specific Interpretation of Kleefstra Syndrome Variants in EHMT1
Authors: Chi Young-In , Jorge Salomão D. , Jensen Davin R. , Smith Brian C. , Volkman Brian F. , Mathison Angela J. , Lomberk Gwen , Zimmermann Michael T. , Urrutia Raul 
Published: September 2023

ABSTRACTThis study investigates the functional significance of assorted variants of uncertain significance (VUS) in euchromatic histone lysine methyltransferase 1 (EHMT1), which is critical for early development and normal physiology. EHMT1 mutations cause Kleefstra syndrome and are linked to various human cancers. However, accurate functional interpretation of these variants are yet to be made, limiting diagnoses and future research. To overcome this, we integrate conventional tools for variant calling with computational biophysics and biochemistry to conduct multi-layered mechanistic analyses of the SET catalytic domain of EHMT1, which is critical for this protein function. We use molecular mechanics and molecular dynamics (MD)-based metrics to analyze the SET domain structure and functional motions resulting from 97 Kleefstra syndrome missense variants within this domain. Our approach allows us to classify the variants in a mechanistic manner into SV (Structural Variant), DV (Dynamic Variant), SDV (Structural and Dynamic Variant), and VUS (Variant of Uncertain Significance). Our findings reveal that the damaging variants are mostly mapped around the active site, substrate binding site, and pre-SET regions. Overall, we report an improvement for this method over conventional tools for variant interpretation and simultaneously provide a molecular mechanism of variant dysfunction.
Spatial landscape of malignant pleural and peritoneal mesothelioma tumor immune microenvironment
Authors: Ma Xiaojun , Lembersky David , Kim Elena S , Bruno Tullia C , Testa Joseph R. , Osmanbeyoglu Hatice U 
Published: September 2023

AbstractImmunotherapies have shown modest clinical benefit thus far for malignant mesothelioma (MM). A deeper understanding of immune cell spatial distribution within the tumor immune microenvironment (TIME) is needed to identify interactions between tumor and different immune cell types that might impact the effectiveness of potential immunotherapies. We performed multiplex immunofluorescence (mIF) using tissue microarrays (TMAs, n=3) of samples from patients with malignant peritoneal (n=25) and pleural (n=88) mesothelioma (MPeM and MPM, respectively) to elucidate the spatial distributions of major immune cell populations and their association with LAG3, BAP1, NF2, and MTAP expression, the latter as a proxy for CDKN2A/B. We also analyzed the relationship between the spatial distribution of major immune cell types with MM patient prognosis and clinical features. The distribution of immune cells within the TIME is similar between MPM and MPeM. However, there is a higher level of interaction between immune cells and tumor cells in MPM than MPeM. Within MPM tumors, there is increased amount of interaction between tumor cells and CD8+T cells in BAP1-low than in BAP1-high expressing tumors. The cell-cell interactions identified in this investigation have potential implications for the immune response against MM tumors and could be a factor in the different behaviors of MPM and MPeM. Our findings provide a valuable resource for the MM cancer research community and exemplifies the utility of spatial resolution within single-cell analyses.Our mesothelioma spatial atlas mIF dataset is available athttps://mesotheliomaspatialatlas.streamlit.app/.
CRISPR-COPIES: Anin silicoplatform for discovery of neutral integration sites for CRISPR/Cas-facilitated gene integration
Authors: Boob Aashutosh Girish , Zhu Zhixin , Intasian Pattarawan , Jain Manan , Petrov Vassily Andrew , Tan Shih-I , Xun Guanhua , Zhao Huimin 
Published: September 2023

AbstractThe CRISPR/Cas system has emerged as a powerful tool for genome editing in metabolic engineering and human gene therapy. However, locating the optimal site on the chromosome to integrate heterologous genes using the CRISPR/Cas system remains an open question. Selecting a suitable site for gene integration involves considering multiple complex criteria, including factors related to CRISPR/Cas-mediated integration, genetic stability, and gene expression. Consequently, identifying such sites on specific or different chromosomal locations typically requires extensive characterization efforts. To address these challenges, we have developed CRISPR-COPIES, aCOmputationalPipeline for theIdentification of CRISPR/Cas-facilitated intEgrationSites. This tool leverages ScaNN, a state-of-the-art model on the embedding-based nearest neighbor search for fast and accurate off-target search and can identify genome-wide intergenic sites for most bacterial and fungal genomes within minutes. As a proof of concept, we utilized CRISPR-COPIES to characterize neutral integration sites in three diverse species: Saccharomyces cerevisiae, Cupriavidus necator, and a human cell line. In addition, we developed a user-friendly web interface for CRISPR-COPIES (https://biofoundry.web.illinois.edu/copies/). We anticipate that CRISPR-COPIES will serve as a valuable tool for targeted DNA integration and aid in the characterization of synthetic biology toolkits, enable rapid strain construction to produce valuable biochemicals and support human gene and cell therapy applications.Graphical abstractOverview and application of CRISPR-COPIES in the field of biotechnology.
Flexible Methods for Standard Error Calculation in digital PCR Experiments
Authors: Chen Yao , De Spiegelaere Ward , Trypsteen Wim , Gleerup David , Vandesompele Jo , Thas Olivier 
Published: September 2023

AbstractDigital PCR (dPCR) is a highly accurate and precise technique for the quantification of target nucleic acid(s) in a biological sample. This digital quantification relies on the binomial or Poisson distribution to estimate the amount of target molecules based on positive and negative partitions. However, the implementation of these distributions require adherence to underlying assumptions that are often neglected, leading to a suboptimal (too optimistic) variance estimation of the target concentration, especially when considering the multiple sources of variation in experimental dPCR setups. Moreover, these parametric methods cannot be easily used for downstream statistical inference when more advanced analysis are required, such as for copy number variation.We evaluated the performance of three new statistical methods (BootsVar, NonPVar, BinomVar) in both simulations and real-life datasets for target and variance estimation in dPCR setups while taking into account a combination of commonly observed sources of experimental variability that can interfere with the underlying assumptions of the current parametric methods.The results demonstrate the capability of the new methods for variance estimation and present a more accurate reflection of the true variability over the classical binomial approach. In addition, these statistical methods are flexible and generic in the way that they work well for the variance estimation of non-linear statistics that work with ratios (e.g. CNV) and for multiplex dPCR setups.In this study, we provide guidelines when to use the binomial-assumption based methods and when the non-parametric one is better to achieve more accurate variance estimates.
Distilling Mechanistic Models From Multi-Omics Data
Authors: Erwin Samantha , Fletcher Joshua R. , Sweeney Daniel C. , Theriot Casey M. , Lanzas Cristina 
Published: September 2023

AbstractHigh-dimensional multi-omics data sets are increasingly accessible and now routinely being generated as part of medical and biological experiments. However, the ability to infer mechanisms of these data remains low due to the abundance of confounding data. The gap between data generation and interpretation highlights the need for strategies to harmonize and distill complex multi-omics data sets into concise, mechanistic descriptions. To this end, a four-step analysis approach for multiomics data is herein demonstrated, comprising: filling missing data and harmonizing data sources, inducing sparsity, developing mechanistic models, and interpretation. This strategy is employed to generate a parsimonious mechanistic model from high-dimensional transcriptomics and metabolomics data collected from a murine model ofClostridioides difficileinfection. This approach highlighted the role of the Stickland reactor in the production of toxins during infection, in agreement with recent literature. The methodology present here is demonstrated to be feasible for interpreting multi-omics data sets and it, to the authors knowledge, one of the first reports of a successful implementation of such a strategy.
Bibliometric and visualized mapping: two decades of lipidomics, with special focus on pregancy and women
Authors: Zhang Lin , Zhou Ying , Zhou Jiashun 
Published: September 2023

AbstractTo perform a bibliometric visualization in lipidomics-related research with two decades. The primary data was retrieved from the Web of Science, three sotwares (VOSviewer, CiteSpace, and R) provided an overview of this field. The countries, institutions, authors, key terms, and keywords were tracked and corresponding mapping was generated. From January 1st in 2001 to March 21th in 2022, 45,325 authors from 234 organizations in 101 countries published 7,338 publications in 382 journals were found.Journal of Lipid Researchwas the most productive (284 publications) and highly cited journal (18,293 citations). We clustered four keywords themes. The niche theme were shotgun lipidomics, tandem mass-spectrometry, and electrospray-ionization. The motor theme were expression, diseases, and inflammation. The emerging or decling theme were identification, mass-spectrometry, and fatty acids.The basic theme were metabolism, cell, and plasma. Though eight categories the lipid were classified, the keywords showed two of which were got more attention for research, fatty acyls and glycerophospholipids. The top 3 lipidomics-favoured diseases were insulin resistance, obesity, and Alzheimer’s disease. The top 3 lipidomics-favoured tissue was plasma, brain, and adipose tissue. Burst citations show “women” and “pregnancy” with the strength of 8.91 and 7.1, both topics may be a potential hotspot in the future.
Involvement of the splicing factor SART1 in the BRCA1-dependent homologous recombination repair of DNA double-strand breaks
Authors: Yamauchi Motohiro , Kato Reona , Yasuhara Takaaki , Uchihara Yuki , Hirakawa Miyako , Ozaki Kie , Abe Yu , Shibata Hiroki , Kawabata-Iwakawa Reika , Shakayeva Aizhan , Kot Palina , Miyagawa Kiyoshi , Suzuki Keiji , Shibata Atsushi , Matsuda Naoki 
Published: September 2023

AbstractAlthough previous studies have reported that pre-mRNA splicing factors (SFs) are involved in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), their exact role in promoting HR remains poorly understood. Here, we showed that SART1, an SF upregulated in several types of cancer, promotes DSB end resection, which is an essential step in HR, without affecting the expression of HR factors. In the promotion of resection, SART1 is epistatic with BRCA1, an HR factor known to promote resection. Mechanistically, SART1 cooperates with BRCA1 to counteract the resection blockade posed by 53BP1 and RIF1. Moreover, SART1 is required for recruitment of the HR-promoting portion of BRCA1 to DSBs. Laser microirradiation experiments revealed that SART1 is recruited to DSBs in a BRCA1-dependent manner, and that the arginine/serine (RS)-rich domain is required for SART1 recruitment to DSBs. We also obtained evidence that SART1 is involved in transcription-associated HR together with BRCA1. Furthermore, chromosome analysis demonstrated that SART1 and BRCA1 epistatically suppressed genomic alterations caused by DSB misrepair in the G2 phase. Collectively, these results indicate that SART1 and BRCA1 cooperatively facilitate resection of DSBs arising in transcriptionally active genomic regions, thereby promoting faithful HR repair of such DSBs and suppressing genome instability.