bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial genome sequencing and analysis of the invasiveMicrostegium vimineum: a resource for systematics, invasion history, and management
Authors: Barrett Craig F. , Ramachandran Dhanushya , Chen Chih-Hui , Corbett Cameron W. , Huebner Cynthia D. , Sinn Brandon T. , Yu Wen-Bin , Suetsugu Kenji 
Published: February 2023

AbstractPremise of the ResearchPlants remain underrepresented among species with sequenced mitochondrial genomes (mitogenomes), due to the difficulty in assembly with short-read technology. Invasive species lag behind crops and other economically important species in this respect, representing a lack of tools for management and land conservation efforts.MethodologyThe mitogenome ofMicrostegium vimineum, one of the most damaging invasive plant species in North America, was sequenced and analyzed using long-read data, providing a resource for biologists and managers. We conducted analyses of genome content, phylogenomic analyses among grasses and relatives based on mitochondrial coding regions, and an analysis of mitochondrial single nucleotide polymorphism in this invasive grass species.Pivotal ResultsThe assembly is 478,010 bp in length and characterized by two large, inverted repeats, and a large, direct repeat. However, the genome could not be circularized, arguing against a “master circle” structure. Long-read assemblies with data subsets revealed several alternative genomic conformations, predominantly associated with large repeats. Plastid-like sequences comprise 2.4% of the genome, with further evidence of Class I and Class II transposable element-like sequences. Phylogenetic analysis placedM. vimineumwith otherMicrostegiumspecies, excludingM. nudum, but with weak support. Analysis of polymorphic sites across 112 accessions ofM. vimineumfrom the native and invasive ranges revealed a complex invasion history.ConclusionsWe present an in-depth analysis of mitogenome structure, content, phylogenetic relationships, and range-wide genomic variation inM. vimineum’sinvasive US range. The mitogenome ofM. vimineumis typical of other andropogonoid grasses, yet mitochondrial sequence variation across the invasive and native ranges is extensive. Our findings suggest multiple introductions to the US over the last century, with subsequent spread, secondary contact, long-distance dispersal, and possibly post-invasion selection on awn phenotypes. Efforts to produce genomic resources for invasive species, including sequenced mitochondrial genomes, will continue to provide tools for their effective management, and to help predict and prevent future invasions.
Histone demethylase KDM2A is a selective vulnerability of cancers relying on alternative telomere maintenance
Authors: Li Fei , Wang Yizhe , Hwang Inah , Jang Ja-Young , Xu Libo , Deng Zhong , Yu Eun Young , Cai Yiming , Wu Caizhi , Han Zhenbo , Huang Yu-Han , Huang Xiangao , Zhang Ling , Yao Jun , Lue Neal F. , Lieberman Paul M. , Ying Haoqiang , Paik Jihye , Zheng Hongwu 
Published: February 2023

AbstractTelomere length maintenance is essential for cellular immortalization and tumorigenesis. 5% - 10% of human cancers rely on a recombination-based mechanism termed alternative lengthening of telomeres (ALT) to sustain their replicative immortality, yet there are currently no targeted therapies. Through CRISPR/Cas9-based genetic screens in an ALT-immortalized isogenic cellular model, here we identify histone lysine demethylase KDM2A as a molecular vulnerability selectively for cells contingent on ALT-dependent telomere maintenance. Mechanistically, we demonstrate that KDM2A is required for dissolution of the ALT-specific telomere clusters following homology-directed telomere DNA synthesis. We show that KDM2A promotes de-clustering of ALT multitelomeres through facilitating isopeptidase SENP6-mediated SUMO deconjugation at telomeres. Inactivation of KDM2A or SENP6 impairs post-recombination telomere de-SUMOylation and thus dissolution of ALT telomere clusters, leading to gross chromosome missegregation and mitotic cell death. These findings together establish KDM2A as a selective molecular vulnerability and a promising drug target for ALT-dependent cancers.
GOLDEN2-like1is sufficient but not necessary for chloroplast biogenesis in mesophyll cells of C4grasses
Authors: Lambret-Frotte Julia , Smith Georgia , Langdale Jane A. 
Published: February 2023

ABSTRACTChloroplasts are the site of photosynthesis. In land plants, chloroplast biogenesis is regulated by a family of transcription factors namedGOLDEN2-like(GLK). In C4grasses, it has been hypothesized that genome duplication events led to the sub-functionalization ofGLKparalogs (GLK1andGLK2) to control chloroplast biogenesis in two distinct cell types: mesophyll and bundle sheath cells. Although previous characterization ofgolden2(g2) mutants in maize has demonstrated a role forGLK2paralogs in regulating chloroplast biogenesis in bundle sheath cells, the function ofGLK1has remained elusive. Here we show that, contrary to expectations,GLK1is not required for chloroplast biogenesis in mesophyll cells of maize. Comparisons between maize andSetaria viridis, which represent two independent C4origins within the Poales, further show that the role ofGLKparalogs in controlling chloroplast biogenesis in mesophyll and bundle sheath cells differs between species. Despite these differences, complementation analysis revealed thatGLK1andGLK2genes from maize are both sufficient to restore functional chloroplast development in mesophyll and bundle sheath cells ofSetaria viridismutants. Collectively our results suggest an evolutionary trajectory in C4grasses whereby both orthologs retained the ability to induce chloroplast biogenesis butGLK2adopted a more prominent developmental role, particularly in relation to chloroplast activation in bundle sheath cells.
Light-Responsive MicroRNAs in Human Retinal Tissue are Differentially Regulated by Distinct Wavelengths of Light
Authors: Celiker Canan , Weissová Kamila , Černá Kateřina Amruz , Oppelt Jan , Šebestíková Jana , Lišková Petra , Bárta Tomáš 
Published: February 2023

AbstractRetinal microRNA (miRNA) molecules play critical roles in a wide range of processes including cell proliferation, cell death, and synaptic plasticity. Recently they have been shown to regulate crucial processes that are associated with perception of light including visual function, light adaptation, and control of genes regulating circadian light entrainment. Despite extensive work on retinal miRNAs in different model organisms, light-regulated miRNAs in human retina are not known. Here, we aim to characterize these miRNAs. We generated light responsive human retinal organoids that express miRNA families and clusters typically found in the retina. Using in-house-developed photostimulation device, we found that 51 miRNAs are up- or downregulated upon brief photostimulation periods. Clustering analysis revealed that only two miRNA families and three clusters are upregulated, while eight families and ten cluster are downregulated upon photostimulation. Additionally, we found that the light-regulated miRNAs have rapid turnover, and their expression is differentially regulated by distinct wavelengths of light. This study demonstrates that only a small subset of miRNAs is light-responsive in human retinal tissue and the generated human retinal organoids are a valuable model for studying the molecular mechanisms of light perception in the retina.
Sulcal variability in anterior lateral prefrontal cortex contributes to variability in reasoning performance among young adults
Authors: Willbrand Ethan H. , Jackson Samantha , Chen Szeshuen , Hathaway Catherine B. , Voorhies Willa I. , Bunge Silvia A. , Weiner Kevin S. 
Published: February 2023

AbstractIdentifying structure-function correspondences is a major goal among biologists, cognitive neuroscientists, and brain mappers. Recent studies have identified relationships between performance on cognitive tasks and the presence or absence of small, shallow indentations, or sulci, of the human brain. Building on the previous finding that the presence of one such sulcus in the left anterior lateral prefrontal cortex (aLPFC) was related to reasoning task performance in children and adolescents, we tested whether this relationship extended to a different sample, age group, and reasoning task. As predicted, the presence of this aLPFC sulcus—the ventral para-intermediate frontal sulcus—was also associated with higher reasoning scores in young adults (ages 22-36). These findings have not only direct developmental, but also evolutionary relevance—as recent work shows that the pimfs-v is exceedingly rare in chimpanzees. Thus, the pimfs-v is a novel developmental, cognitive, and evolutionarily relevant feature that should be considered in future studies examining how the complex relationships among multiscale anatomical and functional features of the brain give rise to abstract thought.
STAT3 protects HSCs from intrinsic interferon signaling and loss of long-term blood-forming activity
Authors: Patel Bhakti , Zhou Yifan , Babcock Rachel L. , Ma Feiyang , Zal Malgorzata A. , Kumar Dhiraj , Medik Yusra B. , Kahn Laura M. , Pineda Josué E. , Park Elizabeth M. , Tang Ximing , Raso Maria Gabriela , Zal Tomasz , Clise-Dwyer Karen , Giancotti Filippo G. , Colla Simona , Watowich Stephanie S. 
Published: February 2023

AbstractSTAT3 function in hematopoietic stem and progenitor cells (HSPCs) has been difficult to discern asStat3deficiency in the hematopoietic system induces systemic inflammation, which can impact HSPC activity. To address this, we established mixed bone marrow (BM) chimeric mice with CreER-mediatedStat3deletion in 20% of the hematopoietic compartment.Stat3-deficient HSPCs had impaired hematopoietic activity and failed to undergo expansion in BM in contrast toStat3-sufficient (CreER) controls. Single-cell RNA sequencing of Lin−ckit+Sca1+BM cells revealed altered transcriptional responses inStat3-deficient hematopoietic stem cells (HSCs) and multipotent progenitors, including intrinsic activation of cell cycle, stress response, and interferon signaling pathways. Consistent with their deregulation,Stat3-deficient Lin−ckit+Sca1+cells accumulated γH2AX over time. Following secondary BM transplantation,Stat3-deficient HSPCs failed to reconstitute peripheral blood effectively, indicating a severe functional defect in the HSC compartment. Our results reveal essential roles for STAT3 in HSCs and suggest the potential for using targeted synthetic lethal approaches with STAT3 inhibition to remove defective or diseased HSPCs.Key PointsSTAT3 is critical for hematopoietic activity and hematopoietic stem cell maintenance in non-inflammatory conditionsSTAT3 has a cell-intrinsic role in the suppression of interferon signaling and myeloid-skewed transcription in hematopoietic stem cells
The balance of acidic and hydrophobic residues predicts acidic transcriptional activation domains from protein sequence
Authors: Kotha Sanjana R. , Staller Max Valentín 
Published: February 2023

AbstractTranscription factors activate gene expression in development, homeostasis, and stress with DNA binding domains and activation domains. Although there exist excellent computational models for predicting DNA binding domains from protein sequence (Stormo, 2013), models for predicting activation domains from protein sequence have lagged behind (Erijman et al., 2020; Ravarani et al., 2018; Sanborn et al., 2021), particularly in metazoans. We recently developed a simple and accurate predictor of acidic activation domains on human transcription factors (Staller et al., 2022). Here, we show how the accuracy of this human predictor arises from the balance between hydrophobic and acidic residues, which together are necessary for acidic activation domain function. When we combine our predictor with the predictions of neural network models trained in yeast, the intersection is more predictive than individual models, emphasizing that each approach carries orthogonal information. We synthesize these findings into a new set of activation domain predictions on human transcription factors.
Inferring a directed acyclic graph of phenotypes from GWAS summary statistics
Authors: Zilinskas Rachel , Li Chunlin , Shen Xiaotong , Pan Wei , Yang Tianzhong 
Published: February 2023

SummaryEstimating phenotype networks is a growing field in computational biology. It deepens the understanding of disease etiology and is useful in many applications. In this study, we present a method that constructs a phenotype network by assuming a Gaussian linear structure model embedding a directed acyclic graph (DAG). We utilize genetic variants as instrumental variables and show how our method only requires access to summary statistics from a genome-wide association study (GWAS) and a reference panel of genotype data. Besides estimation, a distinct feature of the method is its summary statistics-based likelihood ratio test on directed edges. We applied our method to estimate a causal network of 29 cardiovascular-related proteins and linked the estimated network to Alzheimer’s disease (AD). A simulation study was conducted to demonstrate the effectiveness of this method. An R package sumdag implementing the proposed method, all relevant code, and a Shiny application are available athttps://github.com/chunlinli/sumdag.
Defining the structure, signals, and cellular elements of the gastric mesenchymal niche
Authors: Manieri Elisa , Tie Guodong , Seruggia Davide , Madha Shariq , Maglieri Adrianna , Huang Kun , Fujiwara Yuko , Zhang Kevin , Orkin Stuart H. , He Ruiyang , McCarthy Neil , Shivdasani Ramesh A. 
Published: February 2023

SUMMARYPDGFRA-expressing mesenchyme provides a niche for intestinal stem cells. Corresponding compartments are unknown in the stomach, where corpus and antral glandular epithelia have similar niche dependencies but are structurally distinct from the intestine and from each other. Previous studies considered antrum and corpus as a whole and did not assess niche functions. Using high-resolution imaging and sequencing, we identify regional subpopulations and niche properties of purified mouse corpus and antral PDGFRA+cells. PDGFRAHisub-epithelial myofibroblasts are principal sources of BMP ligands in both gastric segments; two molecularly distinct groups distribute asymmetrically along antral glands but together fail to support epithelial organoidsin vitro. In contrast, strategically positioned PDGFRALocells that express CD55 enable corpus and antral organoid growth in the absence of other cellular or soluble factors. Our study provides detailed insights into spatial, molecular, and functional organization of gastric mesenchyme and the spectrum of signaling sources for stem cell support.
Unique Amphipathicα-helix Drives Membrane Insertion and Enzymatic Activity of ATG3
Authors: Nishimura Taki , Lazzeri Gianmarco , Mizushima Noboru , Covino Roberto , Tooze Sharon A. 
Published: February 2023

AbstractAutophagosome biogenesis requires a localized perturbation of lipid membrane dynamics and a unique protein-lipid conjugate. Autophagy-related (ATG) proteins catalyze this biogenesis on cellular membranes, but the underlying molecular mechanism remains unclear. Focusing on the final step of the protein-lipid conjugation reaction, ATG8/LC3 lipidation, we show how membrane association of the conjugation machinery is organized and fine-tuned at the atomistic level. Amphipathicα-helices in ATG3 proteins (AHATG3) are found to have low hydrophobicity and to be less bulky. Molecular dynamics simulations reveal that AHATG3regulates the dynamics and accessibility of the thioester bond of the ATG3∼LC3 conjugate to lipids, allowing covalent lipidation of LC3. Live cell imaging shows that the transient membrane association of ATG3 with autophagic membranes is governed by the less bulky- hydrophobic feature of AHATG3. Collectively, the unique properties of AHATG3facilitate protein- lipid bilayer association leading to the remodeling of the lipid bilayer required for the formation of autophagosomes.TeaserWe uncover the unique biophysical property of amphipathicα-helix essential for autophagy
Thrombin activation of the factor XI dimer is a multi-staged process for each subunit
Authors: Barroeta Awital Bar , Albanese Pascal , Marquart J. Arnoud , Meijers Joost C.M. , Scheltema Richard A. 
Published: February 2023

AbstractFactor XI (FXI), a protein in the intrinsic coagulation pathway, can be activated by two enzymes. In hemostasis, FXI is activated by thrombin, while FXIIa-mediated activation is prothrombotic. The interactions between FXI and its activating enzymes are poorly understood due to their transient nature. Here, we applied structural proteomics, molecular dynamics simulations and binding assays to investigate the interface between thrombin and FXI including the dynamics underlying FXI activation. We demonstrate that activation of FXI is a multi-staged process, where thrombin first binds to Pro520 on FXI, after which it migrates towards the activation site by engaging the apple 1 domain and finally Arg378. We validated with known mutation sites and additionally found that Pro520 is conserved in prekallikrein (PK). This enables binding of thrombin even though it cannot activate PK. Understanding the exact binding of thrombin to FXI points a way for future interventions for bleeding or thrombosis.
Cooperation and cheating orchestrateVibrioassemblages and polymicrobial synergy in oysters infected with OsHV-1 virus
Authors: Oyanedel Daniel , Lagorce Arnaud , Bruto Maxime , Haffner Philippe , Morot Amandine , Dorant Yann , de La Forest Divonne Sébastien , Delavat François , Inguimbert Nicolas , Montagnani Caroline , Morga Benjamin , Toulza Eve , Chaparro Cristian , Escoubas Jean-Michel , Labreuche Yannick , Gueguen Yannick , Vidal-Dupiol Jeremie , de Lorgeril Julien , Petton Bruno , Degremont Lionel , Tourbiez Delphine , Pimparé Léa-Lou , Leroy Marc , Romatif Océane , Pouzadoux Juliette , Mitta Guillaume , Roux Frédérique Le , Charrière Guillaume M. , Travers Marie-Agnès , Destoumieux-Garzón Delphine 
Published: February 2023

AbstractPolymicrobial diseases significantly impact the health of humans and animals but remain understudied in natural systems. We recently described the Pacific Oyster Mortality Syndrome (POMS), a polymicrobial disease that impacts oyster production and is prevalent worldwide. Analysis of POMS-infected oysters on the French North Atlantic coast revealed that the disease involves co-infection with the endemic ostreid herpesvirus 1 (OsHV-1) and virulent bacterial species such asVibrio crassostreae. However, it is unknown whether consistentVibriopopulations are associated with POMS in different regions, howVibriocontribute to POMS, and how they interact with the OsHV-1 virus during pathogenesis.We resolved theVibriopopulation structure in oysters from a Mediterranean ecosystem and investigated their functions in POMS development. We find thatVibrio harveyiandVibrio rotiferianusare the predominant species found in OsHV-1-diseased oysters and show that OsHV-1 is necessary to reproduce the partition of theVibriocommunity observed in the field. By characterizing the interspecific interactions between OsHV-1,V. harveyiandV. rotiferianus, we find that onlyV. harveyisynergizes with OsHV-1. When co-infected, OsHV-1 andV. harveyibehave cooperatively by promoting mutual growth and accelerating oyster death.V. harveyishowed high virulence potential in oysters and dampened host cellular defenses, making oysters a more favorable niche for microbe colonization. We next investigated the interactions underlying the co-occurrence of diverseVibriospecies in diseased oysters. We found thatV. harveyiharbors genes responsible for the biosynthesis and uptake of a key siderophore called vibrioferrin. This important resource promotes the growth ofV. rotiferianus, a cheater that efficiently colonizes oysters during POMS without costly investment in host manipulation nor metabolite sharing.By connecting field-based approaches, laboratory infection assays and functional genomics, we have uncovered a web of interdependencies that shape the structure and function of the POMS pathobiota. We showed that cooperative behaviors contribute to synergy between bacterial and viral co-infecting partners. Additional cheating behaviors further shape the polymicrobial consortium. Controlling such behaviors or countering their effects opens new avenues for mitigating polymicrobial diseases.
RNA-Seq reveals thatPseudomonas aeruginosamounts growth medium-dependent competitive responses when sensing diffusible cues fromBurkholderia cenocepacia
Authors: Leinweber Anne , Laffont Clémentine , Lardi Martina , Eberl Leo , Pessi Gabriella , Kümmerli Rolf 
Published: February 2023

AbstractMost habitats host diverse bacterial communities, offering opportunities for inter-species interactions. While competition might often dominate such interactions, little is known about whether bacteria can sense competitors and mount adequate responses. The competition-sensing hypothesis proposes that bacteria can use cues such as nutrient stress and cell damage to prepare for battle. Here, we tested this hypothesis by measuring transcriptome changes inPseudomonas aeruginosaexposed to the supernatant of its competitorBurkholderia cenocepacia. We found thatP. aeruginosaexhibited significant and growth-medium-dependent transcriptome changes in response to competition. In iron-rich medium,P. aeruginosaup-regulated genes encoding the type-VI secretion system and the siderophore pyoverdine, whereas genes encoding phenazine toxins and hydrogen cyanide were upregulated under iron-limited conditions. Moreover, general stress response and quorum-sensing regulators were upregulated upon supernatant exposure. Altogether, our results reveal nuanced competitive responses ofP. aeruginosawhen confronted withB. cenocepaciasupernatant, integrating both environmental and social cues.
Genome-wide screens for mitonuclear co-regulators uncover links between compartmentalized metabolism and mitochondrial gene expression
Authors: Kramer Nicholas J. , Prakash Gyan , Choquet Karine , Soto Iliana , Petrova Boryana , Merens Hope E. , Kanarek Naama , Churchman L. Stirling 
Published: February 2023

AbstractMitochondrial oxidative phosphorylation (OXPHOS) complexes are assembled from proteins encoded by both nuclear and mitochondrial DNA. These dual-origin enzymes pose a complex gene regulatory challenge for cells, in which gene expression must be coordinated across organelles using distinct pools of ribosomes. How cells produce and maintain the accurate subunit stoichiometries for these OXPHOS complexes remains largely unknown. To identify genes involved in dual-origin protein complex synthesis, we performed FACS-based genome-wide screens analyzing mutant cells with unbalanced levels of mitochondrial- and nuclear-encoded subunits of cytochromecoxidase (Complex IV). We identified novel genes involved in OXPHOS biogenesis, including two uncharacterized genes:PREPLandNME6. We found that PREPL specifically regulates Complex IV biogenesis by interacting with mitochondrial protein synthesis machinery, while NME6, an uncharacterized nucleoside diphosphate kinase (NDPK), controls OXPHOS complex biogenesis through multiple mechanisms reliant on its NDPK domain. First, NME6 maintains local mitochondrial pyrimidine triphosphate levels essential for mitochondrial RNA abundance. Second, through stabilizing interactions with RCC1L, NME6 modulates the activity of mitoribosome regulatory complexes, leading to disruptions in mitoribosome assembly and mitochondrial RNA pseudouridylation. Taken together, we propose that NME6 acts as a link between compartmentalized mitochondrial metabolites and mitochondrial gene expression. Finally, we present these screens as a resource, providing a catalog of genes involved in mitonuclear gene regulation and OXPHOS biogenesis.