bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative Dynamic Analysis ofde novoSphingolipid Biosynthesis inArabidopsis thaliana
Authors: Osinuga Abraham , Solis Ariadna Gonzalez , Cahoon Rebecca E. , Al-Siyabi Adil , Cahoon Edgar B. , Saha Rajib 
Published: December 2023

SummarySphingolipids are pivotal for plant development and stress responses. Growing interest has been directed towards fully comprehending the regulatory mechanisms of the sphingolipid pathway. We explore itsde novobiosynthesis and homeostasis inArabidopsis thalianacell cultures, shedding light on fundamental metabolic mechanisms. Employing15N isotope labeling and quantitative dynamic modeling approach, we developed aregularized and constraint-basedDynamicMetabolicFluxAnalysis (r-DMFA) framework to predict metabolic shifts due to enzymatic changes. Our analysis revealed key enzymes such as sphingoid-base hydroxylase (SBH) and long-chain-base kinase (LCBK) to be critical for maintaining sphingolipid homeostasis. Disruptions in these enzymes were found to affect cellular viability and increase the potential for programmed cell death (PCD). Thus, this work enhances our understanding of sphingolipid metabolism and demonstrates the utility of dynamic modeling in analyzing complex metabolic pathways.
Comparative transcriptomics provides insight into molecular mechanisms of zinc tolerance in the ectomycorrhizal fungusSuillus luteus
Authors: Smith Alexander , Swinnen Janne , Jonckheere Karl , Bazzicalupo Anna , Liao Hui-Ling , Ragland Greg , Colpaert Jan , Lipzen Anna , Tejomurthula Sravanthi , Barry Kerrie , Grigoriev Igor , Ruytinx Joske , Branco Sara 
Published: December 2023

AbstractZinc is a major soil contaminant and high zinc levels can disrupt growth, survival, and reproduction of fungi. Some fungal species have evolved zinc tolerance through cell processes mitigating zinc toxicity, though the genes and detailed mechanisms underlying fungal zinc tolerance remain unexplored. To fill this gap in knowledge, we investigated the gene expression of zinc tolerance in the mycorrhizal fungusSuillus luteus. We found that zinc tolerance in this species is both a constitutive and environmentally dependent trait. Highly differentially expressed genes were predicted to be involved in transmembrane transport, metal chelation, oxidoreductase activity, and signal transduction. Some of these genes were previously reported as candidates forS. luteuszinc tolerance, while others are reported here for the first time. Overall, we foundS. luteuszinc tolerance is associated with differences in expression of genes involved in metal exclusion and immobilization, as well as recognition and mitigation of metal-induced oxidative stress. Our results contribute to understanding the mechanisms of fungal metal tolerance and pave the way for further research on the role of metal tolerance in mycorrhizal associations.
WITHDRAWN: Release of extracellular DNA byPseudomonasspecies as a major determinant for biofilm switching and an early indicator for cell population control
Authors: Kakahi Fatemeh Bajoul , Martinez Juan Andres , Avitia Fabian Moreno , Telek Samuel , Volke Daniel C. , Wirth Nicolas T. , Nikel Pablo I. , Delvigne Frank 
Published: December 2023

Withdrawal StatementThe authors have withdrawn this manuscript due to a duplicate posting of manuscript number BIORXIV/2021/430776. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author. The correct preprint can be found at doi: 10.1101/2021.02.11.430776
SIRPα controls CD47-dependent platelet clearance in mice and humans
Authors: Shoham Maia , Yiu Ying Ying , Hansen Paige S. , Subramaniam Aanya , Broberg Martin , Gars Eric , Raveh Tal ,   FinnGen, Weissman Irving L. , Sinnott-Armstrong Nasa , Krishnan Anandi , Ollila Hanna M. , Tal Michal Caspi 
Published: December 2023

AbstractOver the last decade, more data has revealed that increased surface expression of the “don’t eat me” CD47 protein on cancer cells plays a role in immune evasion and tumor progression, with CD47 blockade emerging as a new therapy in immuno-oncology. CD47 is critical in regulating cell homeostasis and clearance, as binding of CD47 to the inhibitory receptor SIRPα can prevent phagocytosis and macrophage-mediated cell clearance. The purpose of this study was to examine the role of the CD47-SIRPα signal in platelet homeostasis and clearance. Therapeutic reagents targeting the CD47-SIRPα axis are very promising for treatment of hematologic malignancies and solid tumors, but lead to transient anemia or thrombocytopenia in a subset of patients. We found that platelet homeostatic clearance is regulated through the CD47-SIRPα axis and that therapeutic blockade to disrupt this interaction in mice and in humans has a significant impact on platelet levels. Furthermore, we identified genetic variations at theSIRPAlocus that impact platelet levels in humans such that higherSIRPAgene expression is associated with higher platelet levels.SIRPAexpression at either end of the normal range may affect clinical outcomes of treatment with anti-CD47 therapy.Key pointsPlatelet homeostasis is regulated through the CD47-SIRPα axis and therapeutic blockade to disrupt this interaction impacts platelet levelsCommon genetic variants atSIRPAlocus associate with platelet levels
A non-canonical role of somatic CYCLIN D/CYD-1 in oogenesis and reproductive aging, dependent on the FOXO/DAF-16 activation state
Authors: Rautela Umanshi , Sarkar Gautam Chandra , Chaudhary Ayushi , Chatterjee Debalina , Rosh Mohtashim , Arimbasseri Aneeshkumar G. , Mukhopadhyay Arnab 
Published: December 2023

AbstractFor the optimal survival of a species, an organism coordinates its reproductive decisions with the nutrient availability of its niche. Thus, nutrient-sensing pathways like insulin-IGF-1 signaling (IIS) play an important role in modulating cell division, oogenesis, and reproductive aging. Lowering of the IIS leads to the activation of the downstream FOXO transcription factor (TF) DAF-16 inCaenorhabditis eleganswhich promotes oocyte quality and delays reproductive aging. However, less is known about how the IIS axis responds to changes in cell cycle proteins, particularly in the somatic tissues. Here, we show a new aspect of the regulation of the germline by this nutrient- sensing axis. First, we show that the canonical G1-S cyclin,cyclin D/cyd-1, regulates reproductive aging from the uterine tissue of wild-type worms. Then, we show that knocking downcyd-1in the uterine tissue of an IIS receptor mutant arrests oogenesis at the pachytene stage of meiosis-1 in a FOXO/DAF-16-dependent manner. We find that activated FOXO/DAF-16 destroys the somatic gonad tissues like the sheath cells, and transcriptionally prevents the spermatogenesis-to- oogenesis switch to orchestrate this arrest. Deleting FOXO/DAF-16 releases the arrest and restores the somatic gonad but leads to the production of poor-quality oocytes. Together, our study reveals the unrecognized cell non-autonomous interaction of CYD-1 and FOXO/DAF-16 in reproductive aging and the regulation of oogenesis.
Rethinking Dormancy: Antibiotic Persisters are Metabolically Active, Non-Growing Cells
Authors: Rahman K M Taufiqur , Amaratunga Ruqayyah , Butzin Xuan Yi , Singh Abhyudai , Hossain Tahmina , Butzin Nicholas C. 
Published: December 2023

AbstractBacterial persisters are a subpopulation of multidrug-tolerant cells capable of surviving and resuming activity after exposure to bactericidal antibiotic concentrations, contributing to relapsing infections and the development of antibiotic resistance. We challenge the conventional view that persisters are metabolically dormant by providing compelling evidence that an isogenic population ofEscherichia coliremains metabolically active in persistence. Our transcriptomic analysis, conducted at various time points following exposure to bactericidal concentrations of ampicillin (Amp), revealed a number of genes with differential expression over time. Some genes were consistently upregulated in Amp treated persisters compared to the untreated controls, a change that can only occur in metabolically active cells capable of increasing RNA levels. Some of these genes have been previously linked to persister cells, while others have not been associated with them before. If persister cells were metabolically dormant, we would expect minimal changes in the gene network across different time points of Amp treatment. However, network analysis revealed major shifts in gene network activity at various time points of antibiotic exposure. These findings reveal that persisters are metabolically active, non-dividing cells, thereby challenging the notion that they are dormant.Significance statementBacterial persisters are a subpopulation renowned for their multidrug tolerance and remarkable ability to survive bactericidal antibiotic treatments; understanding their formation and long-term survival presents significant challenges. These persisters play a critical role in driving antibiotic resistance, underscoring the urgency of deepening our knowledge about them as the threat of resistance continues to escalate. Our study challenges the long-held assumption that persisters are metabolically inactive and that persisters are not as dormant as previously thought.
Prevalence and characteristics ofPlasmodium vivaxGametocytes in Duffy-positive and Duffy-negative populations across Ethiopia
Authors: Little Ebony , Shenkutie Tassew T. , Negash Meshesha Tsigie , Abagero Beka R. , Abebe Abnet , Popovici Jean , Mekasha Sindew , Lo Eugenia 
Published: December 2023

AbstractPlasmodiumparasites replicate asexually in the human host. The proportion of infections that carries gametocytes is a proxy for human-to-mosquito transmissibility. It is unclear what proportion ofP. vivaxinfections in Duffy-negatives carries gametocytes. This study aims to determine the prevalence ofP. vivaxin Duffy-negatives across broad regions of Ethiopia and characterize parasite stages. Finger-prick blood samples were collected for microscopic and molecular screening ofPlasmodiumparasites and Duffy status of individuals. Molecular screening of plasmodium species and Duffy blood group genotyping was done using SYBR green and Taqman qPCR method. Among the total 447 samples, 414 (92.6%) wereP.vivaxconfirmed and, 16 (3.9%) of them were from Duffy-negatives. Of these, 5/16 (31.3%) Duffy-negativeP.vivax-infected samples were detected with gametocytes. Of the 398 Duffy-positiveP.vivax-infected samples, 150 (37.7%) were detected with gametocytes, slightly higher than that in Duffy-negatives. This study highlights the presence ofP. vivaxgametocytes in Duffy-negative infections, suggestive of human-to-mosquito transmissibility. AlthoughP. vivaxinfections in Duffy-negatives are commonly associated with low parasitemia, some of these infections were shown with relatively high parasitemia and may represent better erythrocyte invasion capability ofP. vivaxand hidden reservoirs that can contribute to transmission. A better understanding ofP. vivaxtransmission biology and gametocyte function particularly in Duffy-negative populations would aid future treatment and management of vivax malaria in Africa
The gut commensalBlautiamaintains colonic mucus function under low fiber consumption through short-chain fatty acid-mediated activation of Ffar2
Authors: Holmberg Sandra M. , Feeney Rachel H. , Prasoodanan P.K. Vishnu , Puértolas-Balint Fabiola , Singh Dhirendra K. , Wongkuna Supapit , Zandbergen Lotte , Hauner Hans , Brandl Beate , Nieminen Anni I. , Skurk Thomas , Schroeder Bjoern O. 
Published: December 2023

AbstractBeneficial gut bacteria are indispensable for developing colonic mucus and fully establishing its protective function against intestinal microorganisms. Low-fiber diet consumption alters the gut bacterial configuration and disturbs this microbe-mucus interaction, but the specific bacteria and microbial metabolites responsible for maintaining mucus function remain poorly understood. By using human-to-mouse microbiota transplantation andex vivoanalysis of colonic mucus function, our proof-of-concept study demonstrates that individuals who increase their daily dietary fiber intake can improve the capacity of their gut microbiota to prevent diet-mediated mucus defects. Mucus growth, a critical feature of intact colonic mucus, correlated with the abundance of the gut commensalBlautia, and supplementation ofBlautia coccoidesto mice confirmed its mucus-stimulating capacity. Mechanistically,B. coccoidesstimulated mucus growth through the production of the short-chain fatty acids propionate and acetate via activation of the short-chain fatty acid receptor Ffar2, which could serve as a new target to restore mucus growth during mucus-associated lifestyle diseases.
A Mutation-driven oncofetal regression fuels phenotypic plasticity in colorectal cancer
Authors: Mzoughi Slim , Schwarz Megan , Wang Xuedi , Demircioglu Deniz , Ulukaya Gulay , Mohammed Kevin , Tullio Federico Di , Company Carlos , Dramaretska Yuliia , Leushacke Marc , Giotti Bruno , Lannagan Tamsin , Lozano-Ojalvo Daniel , Hasson Dan , Tsankov Alexander M. , Sansom Owen J , Marine Jean-Christophe , Barker Nick , Gargiulo Gaetano , Guccione Ernesto 
Published: December 2023

SummaryTargeting cancer stem cells (CSCs) is crucial for effective cancer treatment1. However, the molecular mechanisms underlying resistance to LGR5+CSCs depletion in colorectal cancer (CRC)2,3remain largely elusive. Here, we unveil the existence of a primitive cell state dubbed the oncofetal (OnF) state, which works in tandem with the LGR5+stem cells (SCs) to fuel tumor evolution in CRC. OnF cells emerge early during intestinal tumorigenesis and exhibit features of lineage plasticity. Normally suppressed by the Retinoid X Receptor (RXR) in mature SCs, the OnF program is triggered by genetic deletion of the gatekeeper APC. We demonstrate that diminished RXR activity unlocks an epigenetic circuity governed by the cooperative action of YAP and AP1, leading to OnF reprogramming. This high-plasticity state is inherently resistant to conventional chemotherapies and its adoption by LGR5+CSCs enables them to enter a drug-tolerant state. Furthermore, through phenotypic tracing and ablation experiments, we uncover a functional redundancy between the OnF and stem cell (SC) states and show that targeting both cellular states is essential for sustained tumor regressionin vivo. Collectively, these findings establish a mechanistic foundation for developing effective combination therapies with enduring impact on CRC treatment.
Highly efficient transgenic mouse production using piggyBac and its application to rapid phenotyping at the founder generation
Authors: Okamura Eiichi , Mizuno Seiya , Matsumoto Shoma , Murata Kazuya , Tanimoto Yoko , Tra Dinh Thi Huong , Suzuki Hayate , Kang Woojin , Ema Tomoka , Morimoto Kento , Kato Kanako , Matsumoto Tomoko , Masuyama Nanami , Kijima Yusuke , Morimura Toshifumi , Sugiyama Fumihiro , Takahashi Satoru , Mizutani Eiji , Woltjen Knut , Yachie Nozomu , Ema Masatsugu 
Published: December 2023

AbstractPronuclear microinjection is the most popular method for producing transgenic (Tg) animals. Because the production efficiency is typically less than 20%, phenotypic characterization of Tg animals is generally performed on the next generation (F1) onwards. However, apart from in rodents, in many animal species with long generation times, it is desirable to perform phenotyping in the founder (F0) generation. In this study, we attempted to optimize a method of Tg mouse production to achieve higher Tg production efficiency using piggyBac transposon systems and established optimal conditions under which almost all individuals in the F0 generation were Tg. We also succeeded in generating bacterial artificial chromosome Tg mice with efficiency of approximately 70%. By combining this method with genome editing technology, we established a new strategy to perform phenotyping of mice with tissue-specific knockout using the F0 generation. Taking the obtained findings together, by using this method, experimental research using Tg animals can be carried out more efficiently.
E3 ligase ASB3 downregulates antiviral innate immunity by targeting MAVS for ubiquitin-proteasomal degradation
Authors: Cheng Mingyang , Lu Yiyuan , Wang Jiarui , Wang Haixu , Sun Yu , Zhao Wenhui , Wang Junhong , Shi Chunwei , Luo Jiawei , Gao Ming , Yu Tianxin , Wang Jianzhong , Guan Jiayao , Wang Nan , Yang Wentao , Jiang Yanlong , Huang Haibin , Yang Guilian , Cao Xin , Yang Dongqin , Wang Chunfeng , Zeng Yan 
Published: December 2023

ABSTRACTE3 ubiquitin ligases are very important to regulate antiviral immunity during viral infection. Here, we discovered that Ankyrin repeat and SOCS box-containing protein 3 (ASB3), an E3 ligase, are upregulated in the presence of RNA viruses, particularly Influenza A virus (IAV). Notably, overexpression of ASB3 inhibits type I IFN (IFN-I) responses induced by Sendai virus (SeV) and H9N2, and ablation of ASB3 restores SeV and H9N2 infection-mediated transcription of IFN-β and its downstream interferon-stimulated genes (ISGs). Interestingly, animals lacking ASB3 showed a decreased susceptibility to H9N2 and PR8 infections. Mechanistically, ASB3 interacts with MAVS and directly mediates K48-linked polyubiquitination and degradation of MAVS at K297, thereby inhibiting the phosphorylation levels of TBK1 and IRF3, downregulating downstream antiviral signaling. These findings establish ASB3 as a critical negative regulator in controlling the activation of antiviral signaling and describe a novel function of ASB3 that has not been previously reported.IMPORTANCEIAV is a significant zoonotic pathogen that causes infections of the respiratory system. Hosts have evolved multiple strategies to defend against IAV infection. However, not all host proteins play an active defense role. In this study, we found that the E3 ligase ASB3 regulates antiviral immunity by manipulating MAVS stability. Briefly, overexpression of ASB3 degrades MAVS, thereby promoting viral replication. In contrast, ASB3 deletion restores MAVS expression, upregulating IFN-I responses. Additional research revealed that ASB3 mediates the K48-linked polyubiquitination of MAVS at K297, resulting in ASB3 being degraded via the ubiquitin-proteasome pathway. These findings reveal, for the first time, a novel mechanism by which ASB3 negatively regulates antiviral immunity and provides a potential target for anti-IAV drug development.
Early Embryonic Establishment of Constitutive Heterochromatin Involves H3K14ac-mediated Recruitment of Eggless/SetDB1
Authors: Tang Ruijun , Zhou Mengqi , Chen Yuwei , Jiang Zhenghui , Fan Xunan , Zhang Jingheng , Dong Aiping , Lv Lu , Mao Song , Chen Fang , Min Jinrong , Liu Ke , Yuan Kai 
Published: December 2023

SUMMARYConstitutive heterochromatin, built on various types of repetitive DNA, is a fundamental feature of eukaryotic nucleus essential for transposon silencing and genome stability. However, the molecular programs driving itsde novoestablishment during early embryogenesis remain poorly understood. Here, we show that histone H3 lysine 14 acetylation (H3K14ac) is maternally inherited and partially colocalizes with hallmarks of constitutive heterochromatin, H3 lysine 9 trimethylation (H3K9me3) and its methyltransferase Eggless/SetDB1, around the mid-blastula transition inDrosophilaearly embryos. Concealing H3K14ac by either antibody injection or maternal knockdown of Gcn5 diminishes Eggless/SetDB1 nuclear foci and reduces the deposition of H3K9me3. Structural analysis reveals that Eggless/SetDB1 recognizes H3K14ac via its tandem Tudor domains, and disrupting the binding interface causes defects in Eggless/SetDB1 distribution and derepression of a subset of transposons. Therefore, H3K14ac, a histone modification associated with active transcription, is a crucial piece of the maternal programs that introduce constitutive heterochromatic features to the newly formed zygotic genome.
Alka(e)nes contribute to membrane lipid homeostasis and resilience of photosynthesis to high light in cyanobacteria
Authors: Miao Rui , Légeret Bertrand , Cuine Stéphan , Burlacot Adrien , Lindblad Peter , Li-Beisson Yonghua , Beisson Frédéric , Peltier Gilles 
Published: December 2023

AbstractAlka(e)nes are produced by many living organisms and exhibit diverse physiological roles, reflecting a high functional versatility. Alka(e)nes serve as water proof wax in plants, communicating pheromones for insects, and microbial signaling molecules in some bacteria. Although alka(e)nes have been found in cyanobacteria and algal chloroplasts, a possible role in photosynthesis and chloroplast function remains elusive. In this study, we investigated the consequences of the absence of alka(e)nes on membrane lipid remodeling and photosynthesis using the cyanobacteriaSynechocystisPCC6803 as a model organism. By following the dynamics of membrane lipids and the photosynthetic performance in strains defected and altered in alka(e)ne biosynthesis, we show that a profound remodeling of the membrane lipidome and carotenoid content occur in the absence of alka(e)nes, including a decrease in the membrane carotenoid content, a decrease in some digalactosyldiacylglycerol (DGDG) species and a parallel increase in monogalactosyldiacylglycerol (MGDG) species. Under high light, this effect is accompanied in alka(e)ne deficient strains by a higher susceptibility of photosynthesis and growth, the effect being reversed by expressing an algal photoenzyme producing alka(e)nes from fatty acids. We conclude that alka(e)nes play a crucial role in maintaining lipid homeostasis of photosynthetic membranes, thereby contributing to the proper functioning of photosynthesis, particularly under elevated light intensities.Significance statementWe used cyanobacteria as a model organism to explore the role of alka(e)nes related to photosynthesis. Our findings reveal that the absence of alka(e)nes induces alterations in the composition of membrane lipids and carotenoid content, resulting in an increased susceptibility of photosynthesis. By introducing a fatty acid photodecarboxylase to produce alkanes, we could reverse these effects, highlighting the critical role of alka(e)nes in maintaining lipid balance in photosynthetic membranes and ensuring efficient photosynthesis. Uncovering the physiological role of alka(e)nes provides insights to a better understanding of the widespread presence of genes encoding alka(e)nes-synthesizing enzymes in cyanobacteria and microalgae, organisms of major ecological and evolutionary importance in the global CO2assimilation.