bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new sugar for an old phage: A c-di-GMP dependent polysaccharide pathway sensitizes E. coli for bacteriophage infection
Authors: Sellner Benjamin , Prakapaitė Rūta , van Berkum Margo , Heinemann Matthias , Harms Alexander , Jenal Urs 
Published: September 2021

AbstractBacteriophages are ubiquitous parasites of bacteria and major drivers of bacterial ecology and evolution. Despite an ever-growing interest in their biotechnological and therapeutic applications, detailed knowledge of the molecular mechanisms underlying phage-host interactions remains scarce. Here, we show that bacteriophage N4 exploits a novel surface glycan, NGR, as a receptor to infect its host Escherichia coli. We demonstrate that this process is regulated by the second messenger c-di-GMP and that N4 infection is specifically stimulated by the diguanylate cyclase DgcJ while the phosphodiesterase PdeL effectively protects E. coli from N4-mediated killing. PdeL-mediated protection requires its catalytic activity to reduce c-di-GMP and includes a secondary role as a transcriptional repressor. We demonstrate that PdeL binds to and represses the promoter of the wec operon, which encodes components of the ECA exopolysaccharide pathway. However, only the acetylglucosamine epimerase WecB but none of the other ECA components is required for N4 infection. Based on this, we postulate that NGR is an N-acetylmannosamine-based carbohydrate polymer that is produced and exported to the cell surface of E. coli in a c-di-GMP dependent manner where it serves as a receptor for N4. This novel carbohydrate pathway is conserved in E. coli and other bacterial pathogens, serves as the primary receptor for a range of N4-like bacteriophages, and is induced at elevated temperature and by specific amino acid-based nutrients. These studies provide an entry point into understanding how bacteria use specific regulatory mechanisms to balance costs and benefits of highly conserved surface structures.ImportanceBecause bacterial surface glycans are in direct contact with the environment they can provide essential protective functions during infections or against competing bacteria. But such structures are also ‘Achilles heels’ as they can serve as primary receptors for bacteriophages. Bacteria thus need to carefully control the exposure of conserved surface glycans to balance costs and benefits. Here, we identify a novel exopolysaccharide that is widely conserved in E. coli and is used by N4 and related bacteriophages as primary receptor. We demonstrate that the synthesis of NGR (N4 glycan receptor) is tightly controlled by the second messenger c-di-GMP in a highly specific manner and by a single diguanylate cyclase. These studies provide an example of how bacteria can alleviate the strong selective pressure imposed on them by bacteriophages entering through conserved surface structures by carefully regulating their synthesis and secretion.
BMP7 increases UCP1-dependent and independent thermogenesis with a unique gene expression program in human neck area derived adipocytes
Authors: Shaw Abhirup , Tóth Beáta B , Arianti Rini , Csomós István , Póliska Szilárd , Vámos Attila , Bacso Zsolt , Győry Ferenc , Fésüs László , Kristóf Endre 
Published: September 2021

AbstractWhite adipocytes contribute to energy storage accumulating lipid droplets, whereas brown and beige adipocytes mainly function in dissipating energy as heat primarily via the action of uncoupling protein 1 (UCP1). Bone morphogenic protein 7 (BMP7) has been shown to drive brown adipocyte differentiation in mice. In this study, we have performed global RNA-sequencing and functional assays on adipocytes obtained from subcutaneous (SC) and deep-neck (DN) depots of human neck and differentiated with or without BMP7. We found that BMP7 did not influence differentiation but upregulated browning markers, including UCP1 mRNA and protein. BMP7 also enhanced mitochondrial DNA content, fragmentation, and levels of oxidative phosphorylation complex subunits along with PGC1α and p-CREB upregulation. Furthermore, both UCP1-dependent proton leak and UCP1-independent, creatine driven substrate cycle coupled thermogenesis were augmented upon BMP7 treatment in SC and DN derived adipocytes. The gene expression analysis shed light also on possible role of genes unrelated to thermogenesis so far, including ACAN, CRYAB, and ID1, which were amongst the highest upregulated ones by BMP7 treatment in both types of adipocytes. Together, our study shows that BMP7 strongly upregulates thermogenesis in human neck area derived adipocytes, along with genes, which might have a supporting role in energy expenditure.
The transcriptomic signature of cyclical parthenogenesis
Authors: Huynh Trung Viet , Hall Alexander S. , Xu Sen 
Published: September 2021

AbstractCyclical parthenogenesis, where females can engage in sexual or asexual reproduction depending on environmental conditions, represents a novel reproductive phenotype that emerged during eukaryotic evolution. The fact that environmental conditions can trigger cyclically parthenogens to engage in distinct reproductive modes strongly suggests that gene expression plays a key role in the origin of cyclical parthenogenesis. However, the genetic basis underlying cyclical parthenogenesis remains understudied. In this study we characterize the female transcriptomic signature of sexual vs. asexual reproduction in the cyclically parthenogenetic microcrustacean Daphnia pulex and D. pulicaria. Our analyses of differentially expressed genes, pathway enrichment, and GO term enrichment clearly show that compared to sexual reproduction the asexual reproductive stage is characterized by both the under-regulation of meiosis and cell-cycle genes and the up-regulation of metabolic genes. We suggest that the under-regulation of meiosis and cell-cycle genes is responsible for the origin of parthenogenesis from meiosis, whereas differentially expressed metabolic genes may mediate choice of asexual vs. sexual reproductive pathway. Furthermore, our analyses identify some cases of divergent expression among gene family members (e.g., doublesex, NOTCH2) associated with asexual or sexual reproductive stage, suggesting potential functional divergence among gene family members.
Temporal Changes in Transcripts of MITE Transposable Elements during Rice Endosperm Development
Authors: Nagata Hiroki , Ono Akemi , Tonosaki Kaoru , Kawakatsu Taiji , Yano Kentaro , Kishima Yuji , Kinoshita Tetsu 
Published: September 2021

ABSTRACTThe repression of transcription from transposable elements (TEs) by DNA methylation is necessary to maintain genome integrity and prevent harmful mutations. However, under certain circumstances, TEs are thought to escape from the host defense system and reactivate their transcription. In Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa), DNA demethylases target the sequences derived from TEs in the central cell, the progenitor cell for the endosperm in the female gametophyte. This genome-wide DNA demethylation is also observed in the endosperm after fertilization. In this study, we used a custom microarray to survey the transcripts generated from TEs during the rice endosperm development and at selected timepoints in the embryo as a control. The expression patterns of TE transcripts are dynamically up- and downregulated during endosperm development, especially for miniature inverted-repeat transposable elements (MITEs). Surprisingly, some TE transcripts were directionally controlled, while the other DNA transposons and retrotransposons were not. We also discovered the NF-Y binding motif, CCAAT, in the region near the 5′ terminal inverted repeat of Youren, one of the transcribed MITEs in the endosperm. Our results uncover dynamic changes in TE activity during endosperm development in rice.
miPEP858/miR858-MYB3-PSK4 module regulates growth and development in Arabidopsis
Authors: Badola Poorwa Kamal , Sharma Ashish , Gautam Himanshi , Trivedi Prabodh Kumar 
Published: September 2021

ABSTRACTSmall molecules, peptides and miRNAs, are the crucial regulators of plant growth. Here, we show the importance of cross-talk between miPEP858a/miR858a and Phytosulfokine (PSK4) in regulating plant growth and development in Arabidopsis. Genome-wide expression analysis suggested modulated expression of PSK4 in miR858 mutant and overexpression, miR858OX, plants. The silencing of PSK4 in miR858OX plants compromised the growth, whereas over-expression of PSK4 in miR858 mutant rescued the developmental defects. The exogenous application of synthetic PSK4 further complemented the plant development in mutant plants. Exogenous treatment of synthetic miPEP858a in PSK4 mutant led to clathrin-mediated internalization of the peptide however did not enhance growth as in the case of wild-type plants. We also demonstrate that the MYB3 is an important molecular component participating in miPEP858a/miR858a-PSK4 module. Finally, our work highlights the signalling between miR858/miPEP858-MYB3-PSK4 in modulating the expression of key elements involved in auxin responses leading to the regulation of growth.One-sentence summarySignaling network between small molecules, miPEP858a/miR858a and phytosulfokine, regulates plant growth in Arabidopsis.
Distinct cell adhesion signature defines glioblastoma myeloid-derived suppressor cell subsets
Authors: Bayik Defne , Bartels Cynthia F. , Lovrenert Katreya , Watson Dionysios C. , Zhang Duo , Kay Kristen , Lauko Adam , Johnson Sadie , Lo Alice , McGraw Mary , Grabowski Matthew , Mohammadi Alireza M. , Veglia Filippo , Fan Yi , Vogelbaum Michael A. , Scacheri Peter , Lathia Justin D. 
Published: September 2021

AbstractIncreased myeloid-derived suppressor cell (MDSC) frequency is associated with worse outcomes and poor therapeutic response in glioblastoma (GBM). Monocytic (m) MDSCs represent the predominant subset in the GBM microenvironment. However, the molecular basis of mMDSC enrichment in the tumor microenvironment compared to granulocytic (g) MDSCs has yet to be determined. Here, we report that mMDSCs and gMDSCs display differences in their tumoraccelerating ability, with mMDSCs driving tumor growth in GBM models. Epigenetic assessments indicate enhanced gene accessibility for cell adhesion programs in mMDSCs and higher cellsurface integrin expression in mouse and human mMDSCs. Integrin β1 blockage abrogated the tumor-promoting phenotype of mMDSCs and altered the immune profile in the tumor microenvironment. These findings suggest that integrin β1 expression underlies the enrichment of mMDSCs in tumors and represents a putative immunotherapy target to attenuate myeloid cell-driven immune suppression in GBM.SummaryMyeloid-derived suppressor cells (MDSCs) drive glioblastoma growth; however, the function of specific MDSCs subsets is unclear. Bayik et al. demonstrate that adhesion programs are enhanced in monocytic MDSCs and responsible for their GBM-promoting function.
LORE receptor homomerization is required for 3-hydroxydecanoic acid-induced immune signaling and determines the natural variation of immunosensitivity within the Arabidopsis genus
Authors: Eschrig Sabine , Schäffer Milena , Shu Lin-Jie , Illig Tina , Eibel Sonja , Fernandez Atiara , Ranf Stefanie 
Published: September 2021

SUMMARYThe S-domain-type receptor-like kinase (SD-RLK) LIPOOLIGOSACCHARIDE-SPECIFIC REDUCED ELICITATION (LORE) fromArabidopsis thalianais a pattern recognition receptor that senses medium-chain 3-hydroxy fatty acids, such as 3-hydroxydecanoic acid (3-OH-C10:0), to activate pattern-triggered immunity. Here, we show that LORE homomerization is required to activate 3-OH-C10:0-induced immune signaling.Fluorescence lifetime imaging inNicotiana benthamianademonstrated thatAtLORE homomerizes via the extracellular and transmembrane domains. Co-expression ofAtLORE truncations lacking the intracellular domain exerts a dominant negative effect onAtLORE signaling in bothN. benthamianaandA. thaliana, highlighting that homomerization is essential for signaling.Screening for 3-OH-C10:0-induced reactive oxygen species production revealed natural variation within the Arabidopsis genus.Arabidopsis lyrataandArabidopsis hallerido not respond to 3-OH-C10:0, although both possess a putative LORE orthologue. Both LORE orthologues have defective extracellular domains that bind 3-OH-C10:0 to a similar level but lack the ability to homomerize. Thus, ligand binding is independent of LORE homomerization. Analysis ofAtLORE andAlyrLORE chimera suggests that the loss ofAlyrLORE homomerization is caused by several amino acid polymorphisms across the extracellular domain.Our findings shed light on the activation mechanism of LORE and the loss of 3-OH-C10:0 perception within the Arabidopsis genus.
Temperature and nutrient conditions modify the effects of phenological shifts in predator-prey communities
Authors: Rudolf V.H.W. 
Published: September 2021

AbstractWhile there is mounting evidence indicating that the relative timing of predator and prey phenologies shapes the outcome of trophic interactions, we still lack a comprehensive understanding of how important the environmental context (e.g. abiotic conditions) is for shaping this relationship. Environmental conditions not only frequently drive shifts in phenologies, but they can also affect the very same processes that mediate the effects of phenological shifts on species interactions. Thus, identifying how environmental conditions shape the effects of phenological shifts is key to predict community dynamics across a heterogenous landscape and how they will change with ongoing climate change in the future. Here I tested how environmental conditions shape effects of phenological shifts by experimentally manipulating temperature, nutrient availability, and relative phenologies in two predator-prey freshwater systems (mole salamander-bronze frog vs dragonfly larvae-leopard frog). This allowed me to (1) isolate the effect of phenological shifts and different environmental conditions, (2) determine how they interact, and (3) how consistent these patterns are across different species and environments. I found that delaying prey arrival dramatically increased predation rates, but these effects were contingent on environmental conditions and predator system. While both nutrient addition and warming significantly enhanced the effect of arrival time, their effect was qualitatively different: Nutrient addition enhanced the positive effect of early arrival while warming enhanced the negative effect of arriving late. Predator responses varied qualitatively across predator-prey systems. Only in the system with strong gape-limitation were predators (salamanders) significantly affected by prey arrival time and this effect varied with environmental context. Correlations between predator and prey demographic rates suggest that this was driven by shifts in initial predator-prey size ratios and a positive feedback between size-specific predation rates and predator growth rates. These results highlight the importance of accounting for temporal and spatial correlation of local environmental conditions and gape-limitation in predator-prey systems when predicting the effects of phenological shifts and climate change on predator-prey systems.
Deficiency of Irx5 protects mice from diet-induced obesity and associated metabolic abnormalities
Authors: Son Joe Eun , Kim Kyoung-Han , Hui Chi-chung 
Published: September 2021

AbstractObesity, a leading cause of several metabolic abnormalities, is mainly due to an imbalance of energy homeostasis. IRX3 and IRX5 have been suggested as determinants of obesity in connection with the intronic variants of FTO, the strongest genetic risk factor of polygenic obesity in humans. Although the causal effects of Irx3 on obesity and its related metabolic consequences have been demonstrated in vivo, the metabolic function of Irx5 remains unclear. In this study, using mice homozygous for an Irx5-knockout (Irx5KO) allele, we show a direct link between Irx5 expression and regulation of body mass/composition and energy homeostasis. Irx5KO mice are leaner and resistant to diet-induced obesity and associated metabolic abnormalities, primarily through the loss of adiposity with an increase in basal metabolic rate with adipose thermogenesis and lower food intake. Furthermore, our long-term feeding analysis found that Irx3 mutant mouse lines also have less food intake, indicating that lower caloric intake also contributes to their lean phenotype. Together, these results demonstrate that Irx5 is critical for energy homeostasis and regulation of body mass/composition and suggest that it likely acts in other tissues beyond adipocytes.
Convergent coding of recent and remote fear memory in the basolateral amygdala
Authors: Liu Jianfeng , Totty Michael S. , Melissari Laila , Bayer Hugo , Maren Stephen 
Published: September 2021

AbstractBackgroundIn both rodents and humans, the basolateral amygdala (BLA) is essential for encoding and retrieving conditioned fear memories. Although the BLA is a putative storage site for these memories, recent evidence suggests that they become independent of the BLA with the passage of time.MethodsWe systematically examined the role for the BLA in the retrieval of recent (1 day) and remote (2 weeks) fear memory using optogenetic, electrophysiological, and calcium imaging methods in male and female Long-Evans rats. Critically, we used a behavioral design that permits within-subjects comparison of recent and remote memory at the same time point; freezing behavior served as the index of learned fear.ResultsWe found that BLA c-Fos expression was similar after the retrieval of recent or remote fear memories. Extracellular single-unit recordings in awake, behaving animals revealed that single BLA neurons exhibit robust increases in spike firing to both recent and remote conditional stimuli (CSs). Fiber photometry recordings revealed that these patterns of activity emerge from principal neurons. Consistent with these results, optogenetic inhibition of BLA principal neurons impaired conditioned freezing to both recent and remote CSs. There were no sex differences in any of the measures or manipulations.ConclusionsThese data reveal that BLA neurons encode both recent and remote fear memories, suggesting substantial overlap in the allocation of temporally distinct events. This may underlie the broad generalization of fear memories across both space and time. Ultimately, these results provide evidence that the BLA is a long-term storage site for emotional memories.
Green light perception paved the way for the diversification of GAF domain photoreceptors
Authors: Priyadarshini Nibedita , Steube Niklas , Wiens Dennis , Narikawa Rei , Wilde Annegret , Hochberg Georg K. A. , Enomoto Gen 
Published: September 2021

AbstractPhotoreceptors are proteins that sense incident light and then trigger downstream signaling events. Phytochromes are linear tetrapyrrole-binding photoreceptors present in plants, algae, fungi, and various bacteria. Most phytochromes respond to red and far-red light signals. Among the phytochrome superfamily, cyanobacteria-specific cyanobacteriochromes show much more diverse optical properties covering the entire visible region. Both phytochromes and cyanobacteriochromes share the GAF domain scaffold to cradle the chromophore as the light-sensing region. It is unknown what physiological demands drove the evolution of cyanobacteriochromes in cyanobacteria. Here we utilize ancestral sequence reconstruction and report that the resurrected ancestral cyanobacteriochrome proteins reversibly respond to green and red light signals. pH titration analyses indicate that the deprotonation of the bound phycocyanobilin chromophore enables the photoreceptor to perceive green light. The ancestral cyanobacteriochromes show modest thermal reversion to the green light-absorbing form, suggesting that they evolved to sense green-rich irradiance rather than red light, which is preferentially utilized for photosynthesis. In contrast to plants and green algae, many cyanobacteria can utilize green light for photosynthesis with their special light-harvesting complexes, phycobilisomes. The evolution of green/red sensing cyanobacteriochromes may therefore have allowed ancient cyanobacteria to acclimate to different light environments by rearranging the absorption capacity of the cyanobacterial antenna complex by chromatic acclimation.Significance StatementLight serves as a crucial environmental stimulus affecting the physiology of organisms across all kingdoms of life. Photoreceptors serve as important players of light responses, absorbing light and actuating biological processes. Among a plethora of photoreceptors, cyanobacteriochromes arguably have the wealthiest palette of color sensing, largely contributing to the success of cyanobacteria in various illuminated habitats. Our ancestral sequence reconstruction and the analysis of the resurrected ancestral proteins suggest that the very first cyanobacteriochrome most probably responded to the incident green-to-red light ratio, in contrast to modern red/far-red absorbing plant phytochromes. The deprotonation of the light-absorbing pigment for green light-sensing was a crucial molecular event for the invention of the new class of photoreceptors with their huge color tuning capacity.
The DarTG toxin-antitoxin system provides phage defense by ADP-ribosylating viral DNA
Authors: LeRoux Michele , Srikant Sriram , Littlehale Megan H. , Teodoro Gabriella , Doron Shany , Badiee Mohsen , Leung Anthony K. L. , Sorek Rotem , Laub Michael T. 
Published: September 2021

AbstractToxin-antitoxin (TA) systems are broadly distributed, yet poorly conserved, genetic elements whose biological functions are unclear and controversial. Some TA systems may provide bacteria with immunity to infection by their ubiquitous viral predators, the bacteriophage. To identify TA systems that protect E. coli MG1655 against phage, we searched for those frequently encoded near known phage defense genes in bacterial genomes. Two of the systems tested provide strong protection against phage infection and are homologs of DarTG, a recently discovered family of TA systems whose biological functions and natural activating conditions were unclear. We demonstrate that phage infection triggers the release of DarT toxin, a DNA ADP-ribosyltransferase, to modify viral DNA and prevent replication, thereby blocking the production of mature virions. Phages can evolve to overcome DarTG defense either through mutations to their DNA polymerase or to an anti-DarT factor, gp61.2, encoded by many T-even phages. Collectively, our results indicate that phage defense may be a common function for TA systems and reveal the mechanism by which DarTG systems inhibit phage infection.