bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arabidopsisspliceosome factor SmD3 modulates immunity toPseudomonas syringaeinfection
Authors: Golisz Anna , Krzyszton Michal , Stepien Monika , Dolata Jakub , Piotrowska Justyna , Szweykowska-Kulinska Zofia , Jarmolowski Artur , Kufel Joanna 
Published: August 2021

AbstractSmD3 is a core component of the small nuclear ribonucleoprotein (snRNP) that is essential for pre-mRNA splicing. The role ofArabidopsisSmD3 in plant immunity was assessed by testing sensitivity ofsmd3aandsmd3bmutants toPseudomonas syringaepv.tomato(Pst) DC3000 infection and its pathogenesis effectors flagellin (flg22), EF-Tu (elf18) and coronatine (COR). Bothsmd3mutants exhibited enhanced susceptibility toPstaccompanied by marked changes in the expression of key pathogenesis markers. mRNA levels of these factors were also altered upon treatment withPseudomonaseffectors. We showed that SmD3-b dysfunction impairs mainly stomatal immunity as a result of defects in stomatal development. Our genome-wide transcriptome analysis of thesmd3b-1mutant infected withPstrevealed that lack of SmD3-b deregulates defense againstPstinfection at the transcriptional and posttranscriptional levels including defects in splicing and an altered pattern of alternative splicing. Other changes in thesmd3b-1mutant involved enhanced elf18- and flg22-induced callose deposition, reduction of flg22-triggered production of early ROS and boost of secondary ROS caused byPstinfection. Together, our data indicate that SmD3 contributes to the plant immune response possibly via regulation of mRNA splicing of key pathogenesis factors.
Genome sequences ofAegilopsspecies of section Sitopsis reveal phylogenetic relationships and provide resources for wheat improvement
Authors: Avni Raz , Lux Thomas , Minz-Dub Anna , Millet Eitan , Sela Hanan , Distelfeld Assaf , Deek Jasline , Yu Guotai , Steuernagel Burkhard , Pozniak Curtis , Ens Jennifer , Gundlach Heidrun , Mayer Klaus F. X. , Himmelbach Axel , Stein Nils , Mascher Martin , Spannagl Manuel , Wulff Brande B. H. , Sharon Amir 
Published: August 2021

AbstractAegilopsis a close relative of wheat (Triticumspp.), andAegilopsspecies in the section Sitopsis represent a rich reservoir of genetic diversity for improvement of wheat. To understand their diversity and advance their utilization, we produced whole-genome assemblies ofAe. longissimaandAe. speltoides. Whole-genome comparative analysis, along with the recently sequencedAe. sharonensisgenome, showed that theAe. longissimaandAe. sharonensisgenomes are highly similar and most closely related to the wheat D subgenome. By contrast, theAe. speltoidesgenome is more closely related to the B subgenome. Haplotype block analysis supported the idea thatAe. speltoidesis the closest ancestor of the wheat B subgenome and highlighted variable and similar genomic regions between the threeAegilopsspecies and wheat. Genome-wide analysis of nucleotide-binding site leucine-rich repeat (NLR) genes revealed species-specific and lineage-specific NLR genes and variants, demonstrating the potential ofAegilopsgenomes for wheat improvement.TeaserGenome sequences of Aegilops species provides a key for efficient exploitation of this rich genetic resource in wheat improvement.
The miR-430 locus with extreme promoter density is a transcription body organizer, which facilitates long range regulation in zygotic genome activation
Authors: Hadzhiev Yavor , Wheatley Lucy , Cooper Ledean , Ansaloni Federico , Whalley Celina , Chen Zelin , Gustincich Stefano , Sanges Remo , Burgess Shawn , Beggs Andrew , Müller Ferenc 
Published: August 2021

ABSTRACTIn anamniote embryos the major wave of zygotic genome activation (ZGA) starts during the mid-blastula transition. This major wave of ZGA is facilitated by several mechanisms, including dilution of repressive maternal factors and accumulation of activating transcription factors during the fast cell division cycles preceding the mid-blastula transition. However, a set of genes escape global genome repression and are activated substantially earlier, during what is called, the minor wave of genome activation. While the mechanisms underlying the major wave of genome activation have been studied extensively, the minor wave of genome activation is little understood. In zebrafish the earliest expressed RNA polymerase II (Pol II) transcribed genes are activated in a pair of large transcription bodies depleted of chromatin, abundant in elongating Pol II and nascent RNAs (Hadzhiev et al., 2019; Hilbert et al., 2021). This transcription body includes the miR-430 gene cluster required for maternal mRNA clearance. Here we explored the genomic, chromatin organisation and cis-regulatory mechanisms of the minor wave of genome activation occurring in the transcription body. By long read genome sequencing we identified a remarkable cluster of miR-430 genes with over 300 promoters and spanning 0.6 Mb, which represent the highest promoter density of the genome. We demonstrate that the miR-430 gene cluster is required for the formation of the transcription body and acts as a transcription organiser for minor wave activation of a set of zinc finger genes scattered on the same chromosome arm, which share promoter features with the miR-430 cluster. These promoter features are shared among minor wave genes overall and include the TATA-box and sharp transcription start site profile. Single copy miR-430 promoter transgene reporter experiments indicate the importance of promoter-autonomous mechanisms regulating escape from global repression of the early embryo. These results together suggest that formation of the transcription body in the early embryo is the result of high promoter density coupled to a minor wave-specific core promoter code for transcribing key minor wave ZGA genes, which are required for the overhaul of the transcriptome during early embryonic development.
Blocking cell fusion inhibits age-induced polyploidy and maintains epithelial organization in Drosophila
Authors: Dehn Ari S. , Gogna Navdeep , Nishina Patsy M. , Losick Vicki P. 
Published: August 2021

SummaryA characteristic of normal aging and age-related diseases is the remodeling of a tissue’s cellular organization through polyploid cell growth. Polyploidy arises from an increase in nuclear ploidy or the number of nuclei per cell. However, it is not known whether age-induced polyploidy is an adaption to stressors or a precursor to degeneration. Here, we find that the adult fruit fly’s abdominal epithelium becomes polyploid with age through generation of large multinucleated cells that make up more than 40% of the tissue area. The syncytia arise by cell fusion, not endomitosis. Epithelial multinucleation is also a characteristic of macular degeneration, including Ctnna1tvrm5, a mouse model for pattern dystrophy. Similarly, we find that the knockdown of alpha-catenin enhances multinucleation in the fly epithelium. We further show that age-induced polyploidy can be suppressed by inhibiting cell fusion revealing a means to maintain tissue organization in older animals.
piRNAs regulate a Hedgehog germline-to-soma pro-aging signal
Authors: Shi Cheng , Murphy Coleen T. 
Published: August 2021

AbstractThe reproductive system regulates the aging of the soma through competing anti- and pro-aging signals. Germline removal extends somatic lifespan through conserved pathways including Insulin, mTOR, and steroid signaling, while germline hyperactivity cuts lifespan short through mechanisms that remain elusive. Here, we show that mating-induced germline hyperactivity leads to the dramatic downregulation of piRNAs, which in turn releases silencing of their targets, including the Hedgehog-like ligand encoding genes wrt-1 and wrt-10, ultimately causing somatic collapse and early death. Germline-produced Hedgehog signals require PTR-6 and PTR-16 receptors for mating-induced body shrinking and lifespan shortening. Our results reveal an unconventional role of the piRNA pathway in transcriptional regulation of Hedgehog signaling, as well as a new role of Hedgehog signaling in the regulation of longevity and somatic maintenance. Our data suggest that Hedgehog signaling is controlled by the tunable piRNA pathway to encode the previously unknown germline-to-soma pro-aging signal. Mating-induced downregulation of piRNAs in the germline and subsequent signaling to the soma via the Hedgehog pathway enables the animal to tune its somatic resource allocation in response to germline needs to optimize reproductive timing and survival.
The human inactive X chromosome modulates expression of the active X chromosome
Authors: San Roman Adrianna K. , Godfrey Alexander K. , Skaletsky Helen , Bellott Daniel W. , Groff Abigail F. , Harris Hannah L. , Blanton Laura V. , Hughes Jennifer F. , Brown Laura , Phou Sidaly , Buscetta Ashley , Kruszka Paul , Banks Nicole , Dutra Amalia , Pak Evgenia , Lasutschinkow Patricia C. , Keen Colleen , Davis Shanlee M. , Tartaglia Nicole R. , Samango-Sprouse Carole , Muenke Maximilian , Page David C. 
Published: August 2021

SummaryResearchers have presumed that the “inactive” X chromosome (Xi) has little impact, in trans, on the “active” X (Xa). To test this, we quantified Xi and Xa gene expression in individuals with one Xa and zero to three Xi’s. Our linear modeling revealed modular Xi and Xa transcriptomes and significant Xi-driven expression changes for 38% (162/423) of expressed X-chromosome genes. By integrating allele-specific analyses, we found that modulation of Xa transcript levels by Xi contributes to many of these Xi-driven changes (≥ 121 genes). By incorporating metrics of evolutionary constraint, we identified 10 X-chromosome genes most likely to drive sex differences in common disease, and sex chromosome aneuploidy syndromes. We conclude that human X chromosomes are regulated both in cis, through Xi-wide transcriptional attenuation, and in trans, through positive or negative modulation of individual Xa genes by Xi. The sum of cis and trans effects differs widely among genes.
The Mismatch Between Neuroscience Graduate Training and Professional Skill Sets
Authors: Shah S. , Juavinett A.L. 
Published: August 2021

AbstractUnderstanding the skill sets required for career paths is a prerequisite for preparing students for those careers. Neuroscience career paths are rapidly changing as the field expands and increasingly overlaps with computational and data-heavy job sectors. With the steady growth in neuroscience trainees and the diversification of jobs for those trainees, it is important to assess whether or not our training is matching the skill sets required in the workforce. Here, we surveyed hundreds of neuroscience professionals and graduate students to assess their use and valuation of a range of skills, from bench skills to communication and management. We find that professionals with neuroscience degrees can be clustered into three main groups based on their skill sets: academic research, industry research and technical work, and non-research. Further, we find that while graduate students do not use or highly value management and communication skills, almost all neuroscience professionals report strongly needing those skills. Finally, coding and data analysis skills are widely used in academic and industry research and predict higher salaries. Our findings can help trainees assess their own skill sets as well as encourage educational leaders to offer training in management and communication–skills which may help catapult trainees into the next stages of their careers.
Transcriptome profiling of Candidatus Liberibacter asiaticus in citrus and psyllids
Authors: De Francesco Agustina , Lovelace Amelia H. , Shaw Dipan , Qiu Min , Wang Yuanchao , Gurung Fatta , Ancona Veronica , Wang Chunxia , Levy Amit , Jiang Tao , Ma Wenbo 
Published: August 2021

AbstractCandidatus Liberibacter asiaticus (Las) is an emergent bacterial pathogen that is associated with the devastating citrus Huanglongbing (HLB). Vectored by the Asian citrus psyllid, Las colonizes the phloem tissue of citrus, causing severe damage to infected trees. So far, cultivating pure Las culture in axenic media has not been successful and dual-transcriptome analyses aiming to profile gene expression in both Las and its host(s) have a low coverage of the Las genome due to the low abundance of bacterial RNA in total RNA extracts from infected tissues. Therefore, the lack of a Las transcriptome remains as a significant knowledge gap. Here, we used a bacterial cell enrichment procedure and confidently determined the expression profiles of approximately 84% of the Las genes. Genes that exhibited the highest expression levels in citrus include ion transporters, ferritin, outer membrane porins, and genes involved in phage-related functions, pilus formation, cell wall modification, and stress responses. One hundred and six genes were found to be differentially expressed in citrus vs psyllids. Genes related to transcription/translation and resilience to host defense response were upregulated in citrus; whereas genes involved in energy generation and the flagella system were expressed to higher levels in psyllids. We also determined the relative expression levels of potential Sec-dependent effectors, which are considered as key virulence factors of Las. This work advances our understanding of HLB biology and offers novel insight into the interactions of Las with its plant host and insect vector.
H3-K27M-Mutant Nucleosomes Interact with MLL1 to Shape the Glioma Epigenetic Landscape
Authors: Furth Noa , Algranati Danielle , Dassa Bareket , Beresh Olga , Fedyuk Vadim , Morris Natasha , Kasper Lawryn H. , Jones Dan , Monje Michelle , Baker Suzanne J. , Shema Efrat 
Published: August 2021

AbstractCancer-associated mutations in genes encoding histones dramatically reshape chromatin and support tumorigenesis. Lysine to methionine substitution of residue 27 on histone H3 (K27M) is a driver mutation in high-grade pediatric gliomas, known to abrogate Polycomb Repressive Complex 2 (PRC2) activity. We applied single-molecule systems to image individual nucleosomes and delineate the combinatorial epigenetic patterns associated with H3-K27M expression. We found that chromatin marks on H3-K27M-mutant nucleosomes are dictated both by their incorporation preferences and by intrinsic properties of the mutation. Mutant nucleosomes not only preferentially bind PRC2, but also directly interact with MLL1, thus leading to genome-wide redistribution of H3K4me3. H3-K27M-mediated deregulation of both repressive and active chromatin marks leads to unbalanced ‘bivalent’ chromatin, which may support a poorly differentiated cellular state. This study provides evidence for a direct effect of H3-K27M oncohistone on the MLL1-H3K4me3 pathway and highlights the capability of single-molecule tools to reveal mechanisms of chromatin deregulation in cancer.
The obesity-linked human lncRNA AATBC regulates adipocyte plasticity by stimulating mitochondrial dynamics and respiration
Authors: Giroud Maude , Kotschi Stefan , Kwon Yun , Le Thuc Ophélia , Hoffmann Anne , Gil-Lozano Manuel , Karbiener Michael , Higareda-Almaraz Juan Carlos , Khani Sajjad , Tews Daniel , Fischer-Posovszky Pamela , Sun Wenfei , Dong Hua , Ghosh Adhideb , Wolfrum Christian , Wabitsch Martin , Virtanen Kirsi A. , Blüher Matthias , Nielsen Søren , Zeigerer Anja , García-Cáceres Cristina , Scheideler Marcel , Herzig Stephan , Bartelt Alexander 
Published: August 2021

AbstractAdipocytes are critical regulators of metabolism and energy balance. While white adipocyte dysfunction is a hallmark of obesity-associated disorders, the activation of thermogenic brown and beige adipocytes is linked to improved cardiometabolic health. As adipocytes dynamically adapt to environmental cues by functionally switching between white and thermogenic phenotypes, a molecular understanding of this adipocyte plasticity could help improving energy balance and weight loss. Here, we show that the long non-coding RNA (lncRNA) Apoptosis associated transcript in bladder cancer (AATBC) is a human-specific regulator of adipocyte plasticity. Searching for new human lncRNAs implicated in adipocyte biology we compared transcriptional profiles of human adipose tissues and cultured adipocytes and discovered that AATBC was enriched in thermogenic conditions. Using primary human adipocytes and immortalized human adipocytes we found that gain-of-function of AATBC enhanced the thermogenic phenotype whereas loss-of-function diminished this effect. The AATBC-mediated increase in mitochondrial respiration was linked to a more fragmented mitochondrial network and vice versa. While we found that AATBC is predominantly located in the nucleus, its effect on global transcription was only marginal. As AATBC is specific to humans, we expressed AATBC in adipose tissue of mice to study its systemic impact, which led to lower plasma leptin levels. Interestingly, this association was also present in human subjects, as AATBC in adipose tissue was inversely correlated with plasma leptin levels, body mass index and other measures of metabolic health. In conclusion, AATBC is a novel obesity-linked regulator of adipocyte plasticity and mitochondrial function in humans.
Inhibiting retinoic acid mitigates vision loss in a mouse model of retinal degeneration
Authors: Telias Michael , Sit Kevin , Frozenfar Daniel , Smith Benjamin , Misra Arjit , Goard Michael J , Kramer Richard H 
Published: August 2021

AbstractIn degenerative retinal disorders, rod and cone photoreceptors die, causing vision impairment and blindness. Downstream neurons survive but undergo morphological and physiological remodeling, with some retinal ganglion cells (RGC) exhibiting heightened spontaneous firing. Retinoic acid (RA) has been implicated as the key signaling molecule that induces RGC hyperactivity, obscuring RGC light responses and reducing light avoidance behaviors triggered by residual rods and cones. However, evidence that RA-dependent remodeling corrupts image-forming vision has been lacking. Here we show that disulfiram, an FDA-approved drug that inhibits RA synthesis, and BMS 493, an RA receptor (RAR) inhibitor, reduce RGC hyperactivity and augment image detection in visually impaired mice. Functional imaging of visual cortical neurons shows that disulfiram and BMS 493 sharpen orientation-tuning and strengthen response fidelity to naturalistic scenes. These findings establish a causal link between RA-induced retinal hyperactivity and vision impairment and define molecular targets and candidate drugs for boosting image-forming vision in retinal degeneration.
Planar aggregation of the influenza viral fusion peptide alters membrane structure and hydration, promoting poration
Authors: Rice Amy , Haldar Sourav , Wang Eric , Blank Paul S. , Akimov Sergey A. , Galimzyanov Timur R. , Pastor Richard W. , Zimmerberg Joshua 
Published: August 2021

AbstractTo infect, enveloped viruses employ spike protein, spearheaded by its amphipathic fusion peptide (FP), that upon activation extends out from the viral surface to embed into the target cellular membrane. Here we report that synthesized influenza virus FP are membrane active, generating pores in giant unilamellar vesicles (GUV), and thus potentially explain both influenza virus’ hemolytic activity and the liposome poration seen in cryo-electron tomography. Experimentally, FP were heterogeneously distributed on the GUV at the time of poration. Consistent with this heterogeneous distribution, molecular dynamics (MD) simulations of asymmetric bilayers with different numbers of FP in one leaflet show FP aggregation. At the center of FP aggregates, a profound change in the membrane structure results in thinning, higher water permeability, and curvature. Ultimately, a hybrid bilayer nanodomain can form with one lipidic leaflet and one peptidic leaflet. Membrane elastic theory predicts a reduced barrier to water pore formation when even a dimer of FP thins the membrane as above, and the FP of that dimer tilts, to continue the leaflet bending initiated by the hydrophobic mismatch between the FP dimer and the surrounding lipid.
TNFa and IL-6 promote ex-vivo proliferation of lineage-committed human regulatory T cells
Authors: Skartsis Nikolaos , Peng Yani , Ferreira Leonardo M.R. , Nguyen Vinh , Muller Yannick , Vincenti Flavio , Tang Qizhi 
Published: August 2021

AbstractTreg therapy is being tested in clinical trials in transplantation and autoimmune diseases, however, the impact of inflammation on Tregs is unclear. In this study, we challenged human Tregs ex-vivo with pro-inflammatory cytokines, TNFα and IL-6. These cytokines enhanced Treg proliferation induced by anti-CD3 and anti-CD28 or CD28 superagonist (CD28SA) while maintaining high expression of FOXP3 and HELIOS, demethylated FOXP3 enhancer, and low expression of cytokines IFNg, IL-4 and IL-17. Blocking TNF receptor signaling using etanercept or deletion of TNF receptor 2 using CRISPR/Cas9 blunted Treg proliferation and attenuated FOXP3 and HELIOS expression, revealing the importance of TNFR2 signaling in Treg proliferation and lineage stability. The robust proliferation induced by CD28SA with IL-6 and TNFα may be adopted for the expansion of therapeutic Tregs. Metabolomics analysis showed that Tregs expanded with CD28SA plus cytokines had more active glycolysis and oxidative phosphorylation, increased energy production, and higher antioxidant potential. Finally, CD28SA plus cytokine-expanded Tregs had comparable suppressive activity in vitro and in vivo in a humanized mouse model of graft-versus-host-disease when compared to Tregs expanded using the conventional protocol. These results demonstrate that human Tregs positively respond to proinflammatory cytokines with enhanced proliferation without compromising their lineage identity or function.
NAD kinase promotes Staphylococcus aureus pathogenesis by supporting production of virulence factors and protective enzymes
Authors: Leseigneur Clarisse , Boucontet Laurent , Duchateau Magalie , Pizarro-Cerda Javier , Matondo Mariette , Colucci-Guyon Emma , Dussurget Olivier 
Published: August 2021

AbstractNicotinamide adenine dinucleotide phosphate (NADPH) is the primary electron donor for reductive reactions that are essential for the biosynthesis of major cell components in all organisms. Nicotinamide adenine dinucleotide kinase (NADK) is the only enzyme that catalyzes synthesis of NADP(H) from NAD(H). While the enzymatic properties and physiological functions of NADK have been thoroughly studied, the role of NADK in bacterial pathogenesis remains unknown. Here, we used CRISPR interference to knockdown NADK gene expression to address the role of this enzyme in Staphylococcus aureus pathogenic potential. We find that NADK inhibition drastically decreases mortality of zebrafish infected with S. aureus. Further, we show that NADK promotes S. aureus survival in infected macrophages by protecting bacteria from antimicrobial defense mechanisms. Proteome-wide data analysis revealed that production of major virulence associated factors is sustained by NADK. We demonstrate that NADK is required for expression of the quorum-sensing response regulator AgrA, which controls critical S. aureus virulence determinants. These findings support a key role for NADK in bacteria survival within innate immune cells and the host during infection.