bluuebunny/crossref_metadata_2025_split huggingface dataset:
A ripening-associated ethylene response factor ERF.D7 activates ARF2 orthologs to regulate tomato fruit ripening
Authors: Gambhir Priya , Parida Adwaita Prasad , Singh Vijendra , Raghuvanshi Utkarsh , Kumar Rahul , Sharma Arun Kumar 
Published: July 2022

AbstractDespite the obligatory nature of ethylene to climacteric fruit ripening and the identification of 77 Ethylene Response Factors (ERFs) in the tomato genome, the role of only limited ERFs has been validated in the ripening process. Here, using a comprehensive morpho-physiological, molecular and biochemical approach, we demonstrate the regulatory role of SlERF.D7 in tomato fruit ripening. The expression of SlERF.D7 positively responds to exogenous ethylene and auxin treatments, most likely in a RIN-independent manner. Overexpression of SlERF.D7 promotes ripening and its silencing has the opposite effects. Alterations in its expression modulated ethylene production, pigment accumulation, and fruit firmness. Consistently, genes involved in ethylene biosynthesis and signalling, lycopene biosynthesis, and cell wall loosening were upregulated in the overexpression lines and downregulated in RNAi lines. These transgenic lines also accumulated altered levels of IAA at late-breaker stages. A positive correlation between ARF2 orthologs transcripts and SlERF.D7 mRNA levels and the fact that ARF2A and ARF2B are direct targets of SlERF.D7 underpinned the perturbed auxin-ethylene crosstalk for the altered ripening program observed in the transgenic fruits. Overall, this study uncovers that SlERF.D7 positively regulates SlARF2A/B abundance to amalgamate auxin and ethylene signalling pathways for controlling tomato fruit ripening.HighlightThe present study identifies a new ripening regulator, SlERF.D7, that controls tomato fruit ripening by activating other known-ripening regulators, SlARF2A and SlARF2B.
An RNAi screen reveals common host-virus gene signatures: implication for anti-viral drug discovery
Authors: Shum David , Bhinder Bhavneet , Mahida Jeni , Radu Constantin , Calder Paul A. , Djaballah Hakim 
Published: July 2022

AbstractDengue is the most common mosquito-borne viral disease that in recent years has become a major international public health concern. Dengue is a tropical neglected disease with increasing global incidences, affecting millions of people worldwide, and without the availability of specific treatments to combat it. The identification of host-target genes essential for the virus life cycle, for which effective modulators may already exist, would provide an alternative path to a rapid drug development of the much needed anti-Dengue agents. For this purpose, we performed the first genome-wide RNAi screen, combining two high content readouts for DENV infection (FLUO) and host cell toxicity (NUCL), against an arrayed lentiviral based shRNA library covering 16,000 genes with a redundancy of at least 5 hairpins per gene. The screen identified 1,924 gene candidates in total; of which, 1,730 gene candidates abrogated Dengue infection, while 194 gene candidates were found to enhance its infectivity in HEK293 cells. A first pass clustering analysis of hits revealed a well orchestrated gene-network dependency on host cell homeostasis and physiology triggering distinct cellular pathways for infectivity, replication, trafficking and egress; a second analysis revealed a comprehensive gene signature of 331 genes common to hits identified in 28 published RNAi host-viral interactions screens. Taken together, our findings provide novel antiviral molecular targets with the potential for drug discovery and development.
SAMHD1 controls innate immunity by regulating condensation of immunogenic self RNA
Authors: Maharana Shovamayee , Kretschmer Stefanie , Hunger Susan , Yan Xiao , Kuster David , Traikov Sofia , Zillinger Thomas , Gentzel Marc , Chappidi Nagaraja , Lucas Nadja , Maser Katharina Isabell , Maatz Henrike , Rapp Alexander , Marchand Virginie , Iyer K. Venkatesan , Chhabra Akshita , Chang Young-Tae , Motorin Yuri , Hubner Norbert , Hartmann Gunther , Hyman Anthony , Alberti Simon , Lee-Kirsch Min Ae 
Published: July 2022

AbstractRecognition of pathogen-derived foreign nucleic acids is central to innate immune defense. This requires discrimination between structurally highly similar self and nonself nucleic acids to avoid aberrant inflammatory responses as in the autoinflammatory disorder Aicardi-Goutières syndrome (AGS). How vast amounts of self RNA are shielded from immune recognition to prevent autoinflammation is not fully understood. Here we show that SAM domain and HD domain-containing protein 1 (SAMHD1), one of the AGS-causing genes, functions as a single-stranded RNA (ssRNA) 3’exonuclease, the lack of which causes cellular RNA accumulation. Increased ssRNA in cells leads to dissolution of RNA-protein condensates, which sequester immunogenic double-stranded RNA (dsRNA). Release of sequestered dsRNA from condensates triggers activation of antiviral type I interferon via retinoic acid-inducible gene I-like receptors. Our results establish SAMHD1 as a key regulator of cellular RNA homeostasis and demonstrate that buffering of immunogenic self RNA by condensates regulates innate immune responses.
A universal dynamical metabolic model representing mixotrophic growth of Chlorella sp
Authors: Pessi Bruno Assis , Baroukh Caroline , Bacquet Anais , Bernard Olivier 
Published: July 2022

AbstractAn emerging idea is to couple wastewater treatment and biofuel production using microalgae to achieve higher productivities and lower costs. This paper proposes a metabolic modelling of Chlorella sp. growing on wastes in mixotrophic conditions, accounting also for the possible inhibitory substrates. A metabolic model considering several possible carbon substrates was developed and run. The addition of several organic carbon substrates such as acetate, butyrate or glucose were tested, along with glycerol, a more realistic substrate from an economical point of view. The metabolic model was built using DRUM framework and consists of 188 reactions and 176 metabolites. After a calibration phase, the model was successfully challenged with data from 122 experiments collected from scientific literature in autotrophic, heterotrophic and mixotrophic conditions. The optimal feeding strategy estimated with the model reduces the time to consume the volatile fatty acids from 16 days to 2 days. The high prediction capability of this model opens new routes for enhancing design and operation in waste valorisation using microalgae.Author SummaryWaste valorisation is one of the current envisaged strategies to make renewable processes more economically advantageous. For example, wastewater treatment can be used to produce biohydrogen from bacteria, through a process called dark fermentation, and to cultivate microalgae for biofuel production. Dark fermentation has, as by-products, organic acids that have inhibitory effects on the growth of microalgae, increasing the time to completely treat the waste. Advances in metabolic knowledge and techniques allow for the deployment of new strategies to improve the efficiency of bioprocesses. In this work, we validate a mathematical model of the metabolism of the microalgae genus Chlorella using the DRUM framework for 122 experiments from the scientific literature. This model enables us to apply control and optimisation techniques to provide a strategy to treat wastes coming from dark fermentation processes, overcoming the inhibition of some organic acids. The strategy is able to reduce the time to treat the waste from 16 days to only 2 days. The high prediction capability of this model opens new routes for enhancing design and operation in waste valorisation using microalgae.
Virus-like transposons cross the species barrier and drive the evolution of genetic incompatibilities
Authors: Widen Sonya A. , Bes Israel Campo , Koreshova Alevtina , Krogull Daniel , Burga Alejandro 
Published: July 2022

AbstractHorizontal gene transfer—the movement of genetic material between different species—has been reported across all major eukaryotic lineages, including vertebrates. However, the underlying mechanisms of transfer and their impact on genome evolution are still poorly understood. While studying the evolutionary origin of a selfish element in the nematode C. briggsae, we discovered that Mavericks, ancient viral-like transposons related to giant viruses and virophages, are one of the long-sought vectors of horizontal gene transfer. We found that Mavericks gained a novel herpesvirus-like fusogen in nematodes, leading to the widespread exchange of cargo genes between extremely divergent species, bypassing sexual and genetic barriers spanning hundreds of millions of years. Our results show how the union between viruses and transposons—nature’s melting pot—causes horizontal gene transfer and ultimately genetic incompatibilities in natural populations.
Spatiotemporal properties of glutamate input support direction selectivity in the dendrites of retinal starburst amacrine cells
Authors: Srivastava Prerna , deRosenroll Geoff , Murphy-Baum Benjamin , Michaels Tracy , Matsumoto Akihiro , Yonehara Keisuke , Awatramani Gautam B. 
Published: July 2022

AbstractThe asymmetric summation of kinetically distinct glutamate inputs across the dendrites of retinal “starburst” amacrine cells is proposed to underlie their direction selective properties, but experimentally verifying input kinetics has been a challenge. Here, we used two-photon glutamate sensor (iGluSnFR) imaging to directly measure the input kinetics across individual starburst dendrites. We found that signals measured from proximal dendrites were relatively sustained compared to those measured from distal dendrites. These differences were observed across a range of stimulus sizes and appeared to be shaped mainly by excitatory rather than inhibitory network interactions. Temporal deconvolution analysis suggests that the steady-state vesicle release rate was ∼ 3 times larger at proximal sites compared to distal sites. Using a connectomics-inspired computational model, we demonstrate that input kinetics play an important role in shaping direction selectivity at low stimulus velocities. Together, these results provide direct support for the ‘space-time wiring’ model for direction selectivity.
Bacterial pattern recognition in C. elegans by a nuclear hormone receptor
Authors: Peterson Nicholas D. , Tse Samantha Y. , Huang Qiuyu Judy , Schiffer Celia A. , Pukkila-Worley Read 
Published: July 2022

SUMMARYPattern recognition of bacterial products by host receptors is essential for innate immunity in many metazoans. Curiously, the nematode lineage lost canonical mechanisms of bacterial pattern recognition. Whether other immune receptors evolved in their place is not known. Here, we characterize the first bacterial pattern recognition receptor and its natural ligand in the nematode Caenorhabditis elegans. We show that the C. elegans nuclear hormone receptor NHR-86/HNF4 senses phenazine-1-carboxamide (PCN), a metabolite produced by pathogenic strains of Pseudomonas aeruginosa. PCN binds to the ligand-binding domain of NHR-86/HNF4, a ligand-gated transcription factor, and activates an anti-pathogen transcriptional program in intestinal epithelial cells that provides protection against P. aeruginosa. These data de-orphan a nuclear hormone receptor and demonstrate that surveillance of metabolite signals from bacteria allows nematodes to identify virulent pathogens in their environment that are poised to cause disease.
The CoQ biosynthetic di-iron carboxylate hydroxylase COQ7 is inhibited by in vivo metalation with manganese but remains function by metalation with cobalt
Authors: Wang Ying , Hekimi Siegfried 
Published: July 2022

ABSTRACTCOQ7 is a mitochondrial hydroxylase that catalyzes the penultimate step of the biosynthesis of coenzyme Q (CoQ; ubiquinone). CoQ is an obligate component of the mitochondrial electron transport chain and an antioxidant. CoQ deficiencies due to mutations in CoQ biosynthetic enzymes are severe genetic disorders often manifesting as mitochondrial disease syndrome. COQ7 is part of the relatively rare class of di-iron carboxylate enzymes, which carry out a wide range of reactions. In a previous study we described how COQ7 activity is inhibited in mammalian cells after treatment with iron chelating agents. Here, we report that manganese exposure of mouse cells leads to decreased COQ7 activity and resulting CoQ deficiency, which might participate in manganese toxicity. We find that the presence of cobalt can interfere with the inhibition of COQ7 by manganese. We present evidence that both manganese inhibition and cobalt interference are the result of metal exchange at the di-iron active site of COQ7. We present findings that suggest that 1) cobalt has greater affinity for the active site of COQ7 than both iron and manganese and, 2) that iron replacement by cobalt at the active site preserves catalytic activity.
Evolution of the regulation of developmental gene expression in blind Mexican cavefish
Authors: Leclercq Julien , Torres-Paz Jorge , Policarpo Maxime , Agnès François , Rétaux Sylvie 
Published: July 2022

ABSTRACTChanges in gene expression regulation during development are considered the main drivers of morphological evolution and diversification. Here, we analysed the embryonic transcriptomes of surface-dwelling and blind cave-adapted morphs of the species Astyanax mexicanus and their reciprocal F1 hybrids at tailbud stage. Comparing gene expression in parents and allelic expression ratios in hybrids, we found that ∼20% of the transcriptome is differentially expressed and that cis-regulatory changes are the main contributors to variations in early developmental gene expression in the two morphs. We provide a list of 108 cis-regulated genes that could contribute to cavefish developmental evolution, and further explore the regulatory mechanisms controlling the cellular and regional expression of rx3, a “master eye gene”. Using quantitative embryology approaches after fluorescent in situ hybridisation, cell transplantations and interference with signalling pathways, we show that rx3 cellular levels -controlling optic cell fates-are regulated in cis and in a cell-autonomous manner, whereas the size of rx3 domain -controlling eye size-depends on non-autonomous Wnt signalling. Altogether, we reveal how distinct mechanisms and regulatory modules can regulate developmental gene expression and shape developmental evolution, with negligible contribution of coding mutations.
NudC regulated Lis1 stability is essential for maintenance of dynamic microtubule ends in the axon terminal
Authors: Kawano Dane , Pinter Katherine , Chlebowski Madison , Petralia Ronald S. , Wang Ya-Xian , Nechiporuk Alex V. , Drerup Catherine M 
Published: July 2022

SummaryAxon terminal structure is critical for neuronal function. This cellular compartment houses synaptic terminals and is a site of high metabolic and functional demand. Axon terminals are also the site of a change in microtubule structure within the neuron. Microtubule stability is decreased relative to the axon shaft due to an enrichment of microtubule plus ends and increase in microtubule dynamics. These dynamic microtubule plus ends have many functions including serving as a docking site for the microtubule motor protein complex Cytoplasmic dynein. Here, we report an unexplored function of the dynein motor in axon terminals: regulation of microtubule stability. Using a forward genetic screen, we identified a mutant with abnormal axon terminal structure due to a loss of function mutation in the dynein interacting protein NudC. We show that the primary function of NudC in the axon terminal is as a chaperone for the protein Lis1. Loss of NudC results in decreased Lis1 protein in this neuronal compartment. Decreased Lis1 in nudc mutants causes dynein/dynactin accumulation and increased microtubule stability in axon terminals. Microtubules in the proximal axon are unaffected. Abnormal microtubule stability and structure can be suppressed by pharmacologically inhibiting dynein, implicating excess dynein motor activity as causal in the enhanced axon terminal microtubule stability. Together, our data support a model in which local NudC-Lis1 modulation of dynein motor activity is critical for regulation of microtubule stability in the axon terminal.
Emergence and influence of sequence bias in evolutionarily malleable, mammalian tandem arrays
Authors: Brovkina Margarita V , Chapman Margaret A. , Holding Matthew L. , Clowney E. Josephine 
Published: July 2022

AbstractThe radiation of mammals at the extinction of the dinosaurs produced a plethora of new forms—as diverse as bats, dolphins, and elephants—in only 10-20 million years. Behind the scenes, adaptation to new niches is accompanied by extensive innovation in large families of genes that allow animals to contact the environment, including chemosensors, xenobiotic enzymes, and immune and barrier proteins. Genes in these “outward-looking” families are allelically diverse among humans and exhibit tissue-specific and sometimes stochastic expression. Here, we show that outward-looking genes are clustered in tandem arrays, enriched in AT-biased isochores, and lack CpG islands in their promoters. Models of mammalian genome evolution have not incorporated the sharply different functions and transcriptional patterns of genes in AT-versus GC-biased regions. To examine the relationship between gene family expansion, sequence content, and functional diversification, we use population genetic data and comparative analysis. First, we find that AT bias can emerge with gene family expansionin cis. Second, human genes in AT-biased isochores or with GC-poor promoters experience relatively low rates ofde novopoint mutation today but are enriched for functional variants. Finally, we find that isochores containing gene clusters exhibit low rates of recombination. We hypothesize that the depletion of GC bases in outward-facing gene clusters results from tolerance of sequence variation and low recombination. In turn, high AT content exerts a profound effect on their chromatin organization and transcriptional regulation.
A Sterol-PI(4)P exchanger controls the Tel1/ATM axis of the DNA Damage Response
Authors: Ovejero Sara , Kumanski Sylvain , Soulet Caroline , Azarli Julie , Pardo Benjamin , Santt Olivier , Constantinou Angelos , Pasero Philippe , Moriel-Carretero María 
Published: July 2022

AbstractUpon DNA damage, cells activate the DNA Damage Response (DDR) to coordinate proliferation and DNA repair. Dietary, metabolic, and environmental inputs are emerging as modulators of how DNA surveillance and repair take place. Lipids hold potential to convey these cues, although little is known about how. We observed that lipid droplet (LD) number specifically increased in response to DNA breaks. We show that the selective storage of sterols into these LD concomitantly stabilizes phosphatidyl-4-inositol (PI(4)P) at the Golgi, where it binds the DDR kinase ATM. In turn, this titration attenuates the initial nuclear ATM-driven response to DNA breaks, thus allowing processive repair. Further, manipulating this loop impacts the kinetics of DNA damage signaling and repair in a predictable manner. Thus, our findings have major implications for tackling genetic instability pathologies through dietary and pharmacological interventions.
Size-dependent transition from steady contraction to waves in actomyosin networks with turnover
Authors: Krishna Ashwini , Savinov Mariya , Ierushalmi Niv , Mogilner Alex , Keren Kinneret 
Published: July 2022

AbstractActomyosin networks play essential roles in many cellular processes including intracellular transport, cell division, and cell motility, exhibiting a myriad of spatiotemporal patterns. Despite extensive research, how the interplay between network mechanics, turnover and geometry leads to these different patterns is not well understood. We focus on the size-dependent behavior of contracting actomyosin networks in the presence of turnover, using a reconstituted system based on cell extracts encapsulated in water-in-oil droplets. We find that the system can self-organize into different global contraction patterns, exhibiting persistent contractile flows in smaller droplets and periodic contractions in the form of waves or spirals in larger droplets. The transition between continuous and periodic contraction occurs at a characteristic length scale that is inversely dependent on the network contraction rate. These dynamics are recapitulated by a theoretical model, which considers the coexistence of different local density-dependent mechanical states with distinct rheological properties. The model shows how large-scale contractile behaviors emerge from the interplay between network percolation essential for long-range force transmission and rearrangements due to advection and turnover. Our findings thus demonstrate how varied contraction patterns can arise from the same microscopic constituents, without invoking specific biochemical regulation, merely by changing the system’s geometry.
Molecular evolution of the ependymin-related geneepdl2in African weakly electric fish
Authors: Losilla Mauricio , Gallant Jason R. 
Published: July 2022

AbstractGene duplication and subsequent molecular evolution can give rise to taxon-specific gene specializations. In a previous study, we found evidence that African weakly electric fish (Mormyridae) may have as many as three copies of theepdl2gene, and the expression of twoepdl2genes is correlated with electric signal divergence.Epdl2belongs to the ependymin-related family (EPDR), a functionally diverse family of secretory glycoproteins. In this study, we first describe vertebrate EPDR evolution and then present a detailed evolutionary history ofepdl2in Mormyridae with emphasis on the speciose genusParamormyrops. Using Sanger sequencing, we confirm three apparently functionalepdl2genes inP. kingsleyae. Next, we developed a nanopore-based amplicon sequencing strategy and bioinformatics pipeline to obtain and classify full-lengthepdl2gene sequences (N = 34) across Mormyridae. Our phylogenetic analysis proposes three or fourepdl2paralogs dating from earlyParamormyropsevolution. Finally, we conducted selection tests which detected positive selection around the duplication events and identified ten sites likely targeted by selection in the resulting paralogs. These sites’ locations in our modeled 3D protein structure involve four sites in ligand binding and six sites in homodimer formation. Together, these findings strongly imply thatepdl2genes display signatures of selection-driven functional specialization after tandem duplications in the rapidly speciatingParamormyrops. Considering previous evidence, we propose thatepdl2may contribute to electric signal diversification in mormyrids, an important aspect of species recognition during mating.