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  • Structural basis for transcription complex disruption by the Mfd translocase
    eLife (IF 7.08) Pub Date : 2021-01-22
    Brian T Chait; Elizabeth A Campbell; Eliza Llewellyn; James Chen; Jin Young Kang; Joshua Brewer; Paul D B Olinares; Seth A Darst

    Transcription-coupled repair (TCR) is a sub-pathway of nucleotide excision repair (NER) that preferentially removes lesions from the template-strand (t-strand) that stall RNA polymerase (RNAP) elongation complexes (EC). Mfd mediates TCR in bacteria by removing the stalled RNAP concealing the lesion and recruiting Uvr(A)BC. We used cryo-electron microscopy to visualize Mfd engaging with a stalled EC

    更新日期:2021-01-22
  • Telomeric double-strand DNA-binding proteins DTN-1 and DTN-2 ensure germline immortality in Caenorhabditis elegans
    eLife (IF 7.08) Pub Date : 2021-01-21
    Egor Vorontsov; Hiroki Shibuya; Io Yamamoto; Jingjing Zhang; Kexin Zhang

    Telomeres are nucleoprotein complexes at the ends of chromosomes and are indispensable for the protection and lengthening of terminal DNA. Despite the evolutionarily conserved roles of telomeres, the telomeric double-strand DNA (dsDNA)-binding proteins have evolved rapidly. Here, we identified double-strand telomeric DNA-binding proteins (DTN-1 and DTN-2) in Caenorhabditis elegans as non-canonical

    更新日期:2021-01-22
  • Reciprocal interaction between mesenchymal stem cells and transit amplifying cells regulates tissue homeostasis
    eLife (IF 7.08) Pub Date : 2021-01-22
    Hu Zhao; Jiahui Du; Jifan Feng; Jingyuan Li; Jinzhi He; Junjun Jing; Mark Urata; Paul Sharpe; Thach-Vu Ho; Tingwei Guo; Yang Chai; Yuan Yuan

    Interaction between adult stem cells and their progeny is critical for tissue homeostasis and regeneration. In multiple organs, mesenchymal stem cells (MSCs) give rise to transit amplifying cells (TACs), which then differentiate into different cell types. However, whether and how MSCs interact with TACs remains unknown. Using the adult mouse incisor as a model, we present in vivo evidence that TACs

    更新日期:2021-01-22
  • Survival of the glycosylated
    eLife (IF 7.08) Pub Date : 2021-01-22
    Harry C Blair; Paul H Schlesinger

    Osteocalcin is a bone matrix protein that acts like a hormone when it reaches the blood, and has different effects in mice and humans.

    更新日期:2021-01-22
  • Optogenetic control of PRC1 reveals its role in chromosome alignment on the spindle by overlap length-dependent forces
    eLife (IF 7.08) Pub Date : 2021-01-22
    Ana Milas; Iva M Tolić; Jelena Martinčić; Mihaela Jagrić; Patrik Risteski

    During metaphase, chromosome position at the spindle equator is regulated by the forces exerted by kinetochore microtubules and polar ejection forces. However, the role of forces arising from mechanical coupling of sister kinetochore fibers with bridging fibers in chromosome alignment is unknown. Here we develop an optogenetic approach for acute removal of PRC1 to partially disassemble bridging fibers

    更新日期:2021-01-22
  • Properdin oligomers adopt rigid extended conformations supporting function
    eLife (IF 7.08) Pub Date : 2021-01-22
    Dennis V Pedersen; Gregers R Andersen; Kresten Lindorff-Larsen; Lise Arleth; Martin N Pedersen; Sofia M Mazarakis; Yong Wang

    Properdin stabilizes convertases formed upon activation of the complement cascade within the immune system. The biological activity of properdin depends on the oligomerization state, but whether properdin oligomers are rigid and how their structure links to function remains unknown. We show by combining electron microscopy and solution scattering, that properdin oligomers adopt extended rigid and well-defined

    更新日期:2021-01-22
  • Scleraxis-lineage cell depletion improves tendon healing and disrupts adult tendon homeostasis
    eLife (IF 7.08) Pub Date : 2021-01-22
    Alayna E Loiselle; Anne EC Nichols; Antonion Korcari; Emma Knapp; Katherine T Best; Keshia E Mora; Mark R Buckley; Samantha N Muscat

    Despite the requirement for Scleraxis-lineage (ScxLin) cells during tendon development, the function of ScxLin cells during adult tendon repair, post-natal growth, and adult homeostasis have not been defined. Therefore, we inducibly depleted ScxLin cells (ScxLinDTR) prior to tendon injury and repair surgery and hypothesized that ScxLinDTR mice would exhibit functionally deficient healing compared to

    更新日期:2021-01-22
  • Chemical genetics and proteome-wide site mapping reveal cysteine MARylation by PARP-7 on immune-relevant protein targets
    eLife (IF 7.08) Pub Date : 2021-01-21
    David Hutin; Denis M Grant; Ilsa T Kirby; Ivan Siordia; Jason Matthews; Kelsie M Rodriguez; Larry L David; Marit Rasmussen; Michael Lund Nielsen; Michael S Cohen; Sara C Buch-Larsen

    Poly(ADP-ribose) polymerase 7 (PARP-7) has emerged as a critically important member of a large enzyme family that catalyzes ADP-ribosylation in mammalian cells. PARP-7 is a critical regulator of the innate immune response. What remains unclear is the mechanism by which PARP-7 regulates this process, namely because the protein targets of PARP-7 mono-ADP-ribosylation (MARylation) are largely unknown

    更新日期:2021-01-21
  • Failures of nerve regeneration caused by aging or chronic denervation are rescued by restoring Schwann cell c-Jun
    eLife (IF 7.08) Pub Date : 2021-01-21
    Alastair M Kilpatrick; Cristina Benito; Georg W Otto; Hugo Cabedo; John Svaren; Jose A Gomez-Sanchez; Ki H Ma; Kirolos Michael; Kristjan R Jessen; Laura J Wagstaff; Liam YN Wong; Mark Turmaine; Peter Arthur-Farraj; Rhona Mirsky; Sergio Velasco-Aviles; Shaline V Fazal; Tessa Gordon

    After nerve injury, myelin and Remak Schwann cells reprogram to repair cells specialized for regeneration. Normally providing strong regenerative support, these cells fail in aging animals, and during chronic denervation that results from slow axon growth. This impairs axonal regeneration and causes significant clinical problems. In mice, we find that repair cells express reduced c-Jun protein as regenerative

    更新日期:2021-01-21
  • The RNA-binding protein SFPQ preserves long-intron splicing and regulates circRNA biogenesis in mammals
    eLife (IF 7.08) Pub Date : 2021-01-21
    Eoghan Thomas O'Leary; Karoline Kragh Ebbesen; Lotte Victoria Winther Stagsted; Thomas Birkballe Hansen

    Circular RNAs (circRNAs) represent an abundant and conserved entity of non-coding RNAs; however, the principles of biogenesis are currently not fully understood. Here, we identify two factors, splicing factor proline/glutamine rich (SFPQ) and non-POU domain-containing octamer-binding protein (NONO), to be enriched around circRNA loci. We observe a subclass of circRNAs, coined DALI circRNAs, with distal

    更新日期:2021-01-21
  • Activation of MAP3K DLK and LZK in Purkinje cells causes rapid and slow degeneration depending on signaling strength
    eLife (IF 7.08) Pub Date : 2021-01-21
    Binhai Zheng; Cai Qi; Christopher L Steinke; Erin M Ritchie; Lizhen Chen; Yishi Jin; Yunbo Li

    The conserved MAP3K Dual leucine zipper kinases can activate JNK via MKK4 or MKK7. Vertebrate DLK and LZK share similar biochemical activities and undergo auto-activation upon increased expression. Depending on cell-type and nature of insults DLK and LZK can induce pro-regenerative, pro-apoptotic or pro-degenerative responses, although the mechanistic basis of their action is not well understood. Here

    更新日期:2021-01-21
  • Identification of PARP-7 substrates reveals a role for MARylation in microtubule control in ovarian cancer cells
    eLife (IF 7.08) Pub Date : 2021-01-21
    Bryan A Gibson; Dan Huang; Jayanthi S Lea; Lavanya H Palavalli Parsons; MiKayla S Stokes; Sridevi Challa; Tulip Nandu; W Lee Kraus

    PARP-7 (TiPARP) is a mono(ADP-ribosyl) transferase whose proteins substrates and biological activities are poorly understood. We observed that PARP7 mRNA levels are lower in ovarian cancer patient samples compared to non-cancerous tissue, but PARP-7 protein nonetheless contributes to several cancer-related biological endpoints in ovarian cancer cells (e.g., growth, migration). Global gene expression

    更新日期:2021-01-21
  • The Arabidopsis active demethylase ROS1 cis-regulates defense genes by erasing DNA methylation at promoter-regulatory regions
    eLife (IF 7.08) Pub Date : 2021-01-20
    Delase Amesefe; Emmanuelle Lastrucci; Jingyu Wang; Lionel Navarro; Magali Charvin; Meenu Singla Rastogi; Thierry Halter

    Active DNA demethylation has emerged as an important regulatory process of plant and mammalian immunity. However, very little is known about the mechanisms by which active demethylation controls transcriptional immune reprogramming and disease resistance. Here, we first show that the Arabidopsis active demethylase ROS1 promotes basal resistance towards Pseudomonas syringae by antagonizing RNA-directed

    更新日期:2021-01-20
  • Comparison of induced neurons reveals slower structural and functional maturation in humans than in apes
    eLife (IF 7.08) Pub Date : 2021-01-20
    Anne Weigert; Barbara Treutlein; Benjamin Marco Peter; Elena Taverna; Luise Fast; Maria Schörnig; Nael Nadif Kasri; Sabina Kanton; Sebastian Ebert; Theresa Schaffer; Wulf Hevers; Xiangchun Ju

    We generated induced excitatory neurons (iNeurons, iNs) from chimpanzee, bonobo and human stem cells by expressing the transcription factor neurogenin‑2 (NGN2). Single cell RNA sequencing (scRNAseq) showed that genes involved in dendrite and synapse development are expressed earlier during iNs maturation in the chimpanzee and bonobo than the human cells. In accordance, during the first two weeks of

    更新日期:2021-01-20
  • Metabolomic profiling of rare cell populations isolated by flow cytometry from tissues
    eLife (IF 7.08) Pub Date : 2021-01-20
    Alpaslan Tasdogan; Andrew W DeVilbiss; Jessalyn M Ubellacker; Michalis Agathocleous; Misty S Martin-Sandoval; Sean J Morrison; Thomas P Mathews; Zhiyu Zhao

    Little is known about the metabolic regulation of rare cell populations because most metabolites are hard to detect in small numbers of cells. We previously described a method for metabolomic profiling of flow cytometrically-isolated hematopoietic stem cells (HSCs) that detects 60 metabolites in 10,000 cells (Agathocleous et al., 2017). Here we describe a new method involving hydrophilic liquid interaction

    更新日期:2021-01-20
  • Collateral sensitivity associated with antibiotic resistance plasmids
    eLife (IF 7.08) Pub Date : 2021-01-20
    Aida Alonso-del Valle; Álvaro San Millán; Cristina Herencias; Jana Palkovičová; Jerónimo Rodríguez-Beltrán; Rafael Cantón; Ricardo León-Sampedro

    Collateral sensitivity (CS) is a promising alternative approach to counteract the rising problem of antibiotic resistance (ABR). CS occurs when the acquisition of resistance to one antibiotic produces increased susceptibility to a second antibiotic. Recent studies have focused on CS strategies designed against ABR mediated by chromosomal mutations. However, one of the main drivers of ABR in clinically

    更新日期:2021-01-20
  • Regulatory roles of Escherichia coli 5' UTR and ORF-internal RNAs detected by 3' end mapping
    eLife (IF 7.08) Pub Date : 2021-01-18
    Caroline Esnault; Gabriele Baniulyte; Gisela Storz; Joseph T Wade; Kavya Chegireddy; Molly Monge; Navjot Singh; Philip P Adams; Ryan K Dale

    Many bacterial genes are regulated by RNA elements in their 5´ untranslated regions (UTRs). However, the full complement of these elements is not known even in the model bacterium Escherichia coli. Using complementary RNA-sequencing approaches, we detected large numbers of 3´ ends in 5´ UTRs and open reading frames (ORFs), suggesting extensive regulation by premature transcription termination. We documented

    更新日期:2021-01-19
  • Freshwater monitoring by nanopore sequencing
    eLife (IF 7.08) Pub Date : 2021-01-19
    Andre Holzer; Daniel E Martin-Herranz; Daniel J Kunz; Edward T Tipper; J Jotautas Baronas; Lara Urban; Maximilian R Stammnitz; Michael B Hall; Michael J Scherm; Philipp Braeuninger-Weimer; Surangi N Perera; Susannah J Salter

    While traditional microbiological freshwater tests focus on the detection of specific bacterial indicator species, including pathogens, direct tracing of all aquatic DNA through metagenomics poses a profound alternative. Yet, in situ metagenomic water surveys face substantial challenges in cost and logistics. Here, we present a simple, fast, cost-effective and remotely accessible freshwater diagnostics

    更新日期:2021-01-19
  • Phenotypic and molecular evolution across 10,000 generations in laboratory budding yeast populations
    eLife (IF 7.08) Pub Date : 2021-01-19
    Alex N Nguyen Ba; Alief Moulana; Angela M Phillips; Artur Rego-Costa; Christopher W Bakerlee; Elizabeth R Jerison; Jiseon Min; Juhee Goyal; Julia C Piper; Katherine R Lawrence; Katya Kosheleva; Megan E Dillingham; Michael J McDonald; Michael M Desai; Milo S Johnson; Parris T Humphrey; Ramya Purkanti; Shreyas Gopalakrishnan; Tanush Jagdish

    Laboratory experimental evolution provides a window into the details of the evolutionary process. To investigate the consequences of long-term adaptation, we evolved 205 Saccharomyces cerevisiae populations (124 haploid and 81 diploid) for ~10,000,000 generations in three environments. We measured the dynamics of fitness changes over time, finding repeatable patterns of declining adaptability. Sequencing

    更新日期:2021-01-19
  • The two roles of complex III in plants
    eLife (IF 7.08) Pub Date : 2021-01-19
    Hans-Peter Braun

    Atomic structures of mitochondrial enzyme complexes in plants are shedding light on their multiple functions.

    更新日期:2021-01-19
  • Climate-driven deoxygenation elevates fishing vulnerability for the ocean's widest ranging shark
    eLife (IF 7.08) Pub Date : 2021-01-19
    Ana Couto; António dos Santos; David W Sims; Frederic Vandeperre; Gonzalo Mucientes; Ivo da Costa; Jorge Fontes; Marisa Vedor; Nicolas E Humphries; Nuno Queiroz; Pedro Afonso; Rui Rosa

    Climate-driven expansions of ocean hypoxic zones are predicted to concentrate pelagic fish in oxygenated surface layers, but how expanding hypoxia and fisheries will interact to affect threatened pelagic sharks remains unknown. Here, analysis of satellite-tracked blue sharks and environmental modelling in the eastern tropical Atlantic oxygen minimum zone (OMZ) shows shark maximum dive depths decreased

    更新日期:2021-01-19
  • Highly redundant neuropeptide volume co-transmission underlying episodic activation of the GnRH neuron dendron
    eLife (IF 7.08) Pub Date : 2021-01-19
    Allan Edward Herbison; H James McQuillan; Isaiah Cheong; Michel K Herde; Robert Porteous; Sabine Hessler; Shel-Hwa Yeo; Xinhuai Liu

    The necessity and functional significance of neurotransmitter co-transmission remains unclear. The glutamatergic 'KNDy' neurons co-express kisspeptin, neurokinin B (NKB) and dynorphin and exhibit a highly stereotyped synchronized behavior that reads out to the gonadotropin-releasing hormone (GnRH) neuron dendrons to drive episodic hormone secretion. Using expansion microscopy, we show that KNDy neurons

    更新日期:2021-01-19
  • Behavioral role of PACAP reflects its selective distribution in glutamatergic and GABAergic neuronal subpopulations
    eLife (IF 7.08) Pub Date : 2021-01-19
    Charles R Gerfen; Lee E Eiden; Lilian Zavala; Limei Zhang; Rafael A Barrio; Sunny Z Jiang; Vito S Hernandez

    The neuropeptide PACAP, acting as a co-transmitter, increases neuronal excitability, which may enhance anxiety and arousal associated with threat conveyed by multiple sensory modalities. The distribution of neurons expressing PACAP and its receptor, PAC1, throughout the mouse nervous system was determined, in register with expression of glutamatergic and GABAergic neuronal markers, to develop a coherent

    更新日期:2021-01-19
  • Atomic structures of respiratory complex III2, complex IV, and supercomplex III2-IV from vascular plants
    eLife (IF 7.08) Pub Date : 2021-01-19
    Fei Guo; James A Letts; Maria Maldonado

    Mitochondrial complex III (CIII2) and complex IV (CIV), which can associate into a higher-order supercomplex (SC III2+IV), play key roles in respiration. However, structures of these plant complexes remain unknown. We present atomic models of CIII2, CIV, and SC III2+IV from Vigna radiata determined by single-particle cryoEM. The structures reveal plant-specific differences in the MPP domain of CIII2

    更新日期:2021-01-19
  • Serotonin 2A receptor signaling coordinates central metabolic processes to modulate aging in response to nutrient choice
    eLife (IF 7.08) Pub Date : 2021-01-19
    Daniel EL Promislow; Humza A Shaukat; Kristina J Weaver; Maria Tjilos; Marta L Plumoff; Scott D Pletcher; Yang Lyu

    It has been recognized for nearly a century that diet modulates aging. Despite early experiments suggesting that reduced caloric intake augmented lifespan, accumulating evidence indicates that other characteristics of the diet may be equally or more influential in modulating aging. We demonstrate that behavior, metabolism, and lifespan in Drosophila are affected by whether flies are provided a choice

    更新日期:2021-01-19
  • Evidence for adaptive evolution in the receptor-binding domain of seasonal coronaviruses OC43 and 229E
    eLife (IF 7.08) Pub Date : 2021-01-19
    Kathryn E Kistler; Trevor Bedford

    Seasonal coronaviruses (OC43, 229E, NL63 and HKU1) are endemic to the human population, regularly infecting and reinfecting humans while typically causing asymptomatic to mild respiratory infections. It is not known to what extent reinfection by these viruses is due to waning immune memory or antigenic drift of the viruses. Here, we address the influence of antigenic drift on immune evasion of seasonal

    更新日期:2021-01-19
  • fruitless tunes functional flexibility of courtship circuitry during development
    eLife (IF 7.08) Pub Date : 2021-01-19
    Dandan Chen; Jie Cao; Jie Chen; Qionglin Peng; Sihui Jin; Xiaoxiao Ji; Yufeng Pan

    Drosophila male courtship is controlled by the male-specific products of the fruitless (fruM) gene and its expressing neuronal circuitry. fruM is considered a master gene that controls all aspects of male courtship. By temporally and spatially manipulating fruM expression, we found that fruM is required during a critical developmental period for innate courtship towards females, while its function

    更新日期:2021-01-19
  • Endothelial cell type-specific molecular requirements for angiogenesis drive fenestrated vessel development in the brain
    eLife (IF 7.08) Pub Date : 2021-01-18
    Rachael E Quick; Ryota L Matsuoka; Sweta Parab

    Vascular endothelial cells (vECs) in the brain exhibit structural and functional heterogeneity. Fenestrated, permeable brain vasculature mediates neuroendocrine function, body-fluid regulation, and neural immune responses, however its vascular formation remains poorly understood. Here we show that specific combinations of vascular endothelial growth factors (Vegfs) are required to selectively drive

    更新日期:2021-01-18
  • Antagonism between Germ cell-less and Torso regulates transcriptional quiescence underlying germline/soma distinction
    eLife (IF 7.08) Pub Date : 2021-01-18
    Dorothy A Lerit; Elias A Castro; Girish Deshpande; Gretchen Kappes; Lauren R Lym; Lillian Wilkins; Megan M Colonnetta; Paul Schedl; Pearl Ryder

    Transcriptional quiescence, an evolutionarily conserved trait, distinguishes the embryonic primordial germ cells
(PGCs) from their somatic neighbors. In Drosophila melanogaster, PGCs from embryos maternally compromised for germ cell-less (gcl) misexpress somatic genes, possibly resulting in PGC loss. Recent studies documented a requirement for Gcl during proteolytic degradation of the terminal patterning

    更新日期:2021-01-18
  • Equity, Diversity and Inclusion: Racial inequity in grant funding from the US National Institutes of Health
    eLife (IF 7.08) Pub Date : 2021-01-18
    Michael A Taffe; Nicholas W Gilpin

    Biomedical science and federal funding for scientific research are not immune to the systemic racism that pervades American society. A groundbreaking analysis of NIH grant success revealed in 2011 that grant applications submitted to the National Institutes of Health in the US by African-American or Black Principal Investigators (PIs) are less likely to be funded than applications submitted by white

    更新日期:2021-01-18
  • Ablation of STAT3 in Purkinje cells reorganizes cerebellar synaptic plasticity in long-term fear memory network
    eLife (IF 7.08) Pub Date : 2021-01-18
    Jaeyong Choi; Jeong-Kyu Han; Jong-Il Kim; Sang Jeong Kim; Sang-Kyu Ye; Sun-Ho Kwon; Yong Gyu Kim; Yong-Seok Lee

    Emotional memory processing engages a large neuronal network of brain regions including the cerebellum. However, the molecular and cellular mechanisms of the cerebellar cortex modulating the fear memory network are unclear. Here, we illustrate that synaptic signaling in cerebellar Purkinje cells (PCs) via STAT3 regulates long-term fear memory. Transcriptome analyses revealed that PC-specific STAT3

    更新日期:2021-01-18
  • Loss of FLCN-FNIP1/2 induces a non-canonical interferon response in human renal tubular epithelial cells
    eLife (IF 7.08) Pub Date : 2021-01-18
    Arjan C Houweling; Connie R Jimenez; Denise Westland; Franziska Böttger; Fried JT Zwartkruis; Hanne EJ Meijers-Heijboer; Iris E Glykofridis; Irma van de Beek; Jaco C Knol; Jarno Drost; Jesper A Balk; Martin A Rooimans; Pino J Poddighe; Puck Veen; Renee X de Menezes; Rob MF Wolthuis; Sander R Piersma; Saskia E van Mil; Sepide Derakhshan; Sinéad M Lougheed; Thang V Pham

    Germline inactivating mutations in Folliculin (FLCN) cause Birt–Hogg–Dubé (BHD) syndrome, a rare autosomal dominant disorder predisposing to kidney tumors. FLCN is a conserved, essential gene linked to diverse cellular processes but the mechanisms by which FLCN prevents kidney cancer remain unknown. Here we show that deleting FLCN activates TFE3, upregulating its downstream E-box genes in human renal

    更新日期:2021-01-18
  • Repeated outbreaks drive the evolution of bacteriophage communication
    eLife (IF 7.08) Pub Date : 2021-01-18
    Glenn A Mulder; Hilje M Doekes; Rutger Hermsen

    Recently, a small-molecule communication mechanism was discovered in a range of Bacillus-infecting bacteriophages, which these temperate phages use to inform their lysis-lysogeny decision. We present a mathematical model of the ecological and evolutionary dynamics of such viral communication, and show that a communication strategy in which phages use the lytic cycle early in an outbreak (when susceptible

    更新日期:2021-01-18
  • Biological constraints on GWAS SNPs at suggestive significance thresholds reveal additional BMI loci
    eLife (IF 7.08) Pub Date : 2021-01-18
    Alessandra Chesi; Andrew D Wells; Chiara Lasconi; Chun Su; Claudia A Doege; Diana L Cousminer; James A Pippin; Kenyaita M Hodge; Kurt D Hankenson; Matthew C Pahl; Matthew E Johnson; Michelle E Leonard; Reza K Hammond; Rudolph L Leibel; Struan FA Grant; Sumei Lu; Yadav Wagley

    To uncover novel significant association signals (P<5x10-8), GWAS requires increasingly larger sample sizes to overcome statistical correction for multiple testing. As an alternative, we aimed to identify associations among suggestive signals (5x10-8 ≤ P < 5x10-4) in increasingly powered GWAS efforts using chromatin accessibility and direct contact with gene promoters as biological constraints. We

    更新日期:2021-01-18
  • Bi-channel Image Registration and Deep-learning Segmentation (BIRDS) for efficient, versatile 3D mapping of mouse brain
    eLife (IF 7.08) Pub Date : 2021-01-18
    Chunyu Fang; Peng Fei; Weilin Zeng; Xiaodan Yang; Xuechun Wang; Yunyun Han

    We have developed an open-source software called BIRDS (bi-channel image registration and deep-learning segmentation) for the mapping and analysis of 3D microscopy data and applied this to the mouse brain. The BIRDS pipeline includes image pre-processing, bi-channel registration, automatic annotation, creation of a 3D digital frame, high-resolution visualization, and expandable quantitative analysis

    更新日期:2021-01-18
  • Global and local tension measurements in biomimetic skeletal muscle tissues reveals early mechanical homeostasis
    eLife (IF 7.08) Pub Date : 2021-01-18
    Alejandro Jurado; Arne D Hofemeier; Bernhard Wallmeyer; Jörg Enderlein; Majid Ebrahimi; Mohammad Ebrahim Afshar; Nazar Oleksiievets; Penney M Gilbert; Roman Tsukanov; Tamara Limón; Till Moritz Muenker; Timo Betz

    Tension and mechanical properties of muscle tissue are tightly related to proper skeletal muscle function, which makes experimental access to the biomechanics of muscle tissue formation a key requirement to advance our understanding of muscle function and development. Recently developed elastic in vitro culture chambers allow for raising 3D muscle tissue under controlled conditions and to measure global

    更新日期:2021-01-18
  • Cytomegalovirus restricts ICOSL expression on antigen presenting cells disabling T cell co-stimulation and contributing to immune evasion
    eLife (IF 7.08) Pub Date : 2021-01-18
    Ana Angulo; Annette Oxenius; Astrid Krmpotic; Guillem Angulo; Hartmut Hengel; Jelena Zeleznjak; Joan Puñet-Ortiz; Martin Messerle; Pablo Engel; Pablo Martínez-Vicente; Stipan Jonjic

    Viral infections are controlled, and very often cleared, by activated T lymphocytes. The inducible co-stimulator (ICOS) mediates its functions by binding to its ligand ICOSL, enhancing T-cell activation and optimal germinal center (GC) formation. Here, we show that ICOSL is heavily downmodulated during infection of antigen presenting cells by different herpesviruses. We found that, in murine cytomegalovirus

    更新日期:2021-01-18
  • Modeling transfer of vaginal microbiota from mother to infant in early life
    eLife (IF 7.08) Pub Date : 2021-01-15
    Asker Daniel Brejnrod; Christina Balle; Hans Bisgaard; Jakob Stokholm; Jonathan Thorsen; Karen Angeliki Krogfelt; Martin Steen Mortensen; Morten Arendt Rasmussen; Søren Johannes Sørensen

    Early-life microbiota has been linked to the development of chronic inflammatory diseases. It has been hypothesized that maternal vaginal microbiota is an important initial seeding source and therefore might have lifelong effects on disease risk. To understand maternal vaginal microbiota’s role in seeding the child’s microbiota and the extent of delivery mode-dependent transmission, we studied 665

    更新日期:2021-01-15
  • Female-biased upregulation of insulin pathway activity mediates the sex difference in Drosophila body size plasticity
    eLife (IF 7.08) Pub Date : 2021-01-15
    Bruno Hudry; Charlotte Chao; Elizabeth J Rideout; George P Brownrigg; Irene Miguel-Aliaga; Jason W Millington; Lianna W Wat; Paige J Basner-Collins; Ziwei Sun

    Nutrient-dependent body size plasticity differs between the sexes in most species, including mammals. Previous work in Drosophila showed that body size plasticity was higher in females, yet the mechanisms underlying increased female body size plasticity remain unclear. Here, we discover that a protein-rich diet augments body size in females and not males because of a female-biased increase in activity

    更新日期:2021-01-15
  • Bi-fated tendon-to-bone attachment cells are regulated by shared enhancers and KLF transcription factors
    eLife (IF 7.08) Pub Date : 2021-01-15
    Axel Visel; Dena Leshkowitz; Elazar Zelzer; Hadas Keren-Shaul; Ido Amit; Lydia Farack; Marco Osterwalder; Ronnie Blecher-Gonen; Shalev Itzkovitz; Shani Ben-Moshe; Sharon Krief; Shiri Kult; Svetalana Markman; Terence D Capellini; Tomer-Meir Salame; Tsviya Olender

    The mechanical challenge of attaching elastic tendons to stiff bones is solved by the formation of a unique transitional tissue. Here, we show that murine tendon-to-bone attachment cells are bi-fated, activating a mixture of chondrocyte and tenocyte transcriptomes, under regulation of shared regulatory elements and Krüppel-like factors (KLFs) transcription factors. High-throughput bulk and single-cell

    更新日期:2021-01-15
  • A flagellate-to-amoeboid switch in the closest living relatives of animals
    eLife (IF 7.08) Pub Date : 2021-01-15
    Danielle C Spitzer; Marvin Albert; Maxwell C Coyle; Nicole King; Thibaut Brunet; William Roman

    Amoeboid cells are fundamental to animal biology and broadly distributed across animal diversity, but their evolutionary origin is unclear. The closest living relatives of animals, the choanoflagellates, display a polarized cell architecture (with an apical flagellum encircled by microvilli) that closely resembles that of epithelial cells and suggests homology, but this architecture differs strikingly

    更新日期:2021-01-15
  • The orchestrated cellular and molecular responses of the kidney to endotoxin define a precise sepsis timeline
    eLife (IF 7.08) Pub Date : 2021-01-15
    Amy Zollman; Bernhard Maier; Danielle Janosevic; Farooq Syed; Hongyu Gao; Jered Myslinski; Kimberly S Collins; Michael T Eadon; Pierre C Dagher; Ricardo Melo Ferreira; Seth Winfree; Takashi Hato; Tarek M El-Achkar; Thomas W McCarthy; Xiaoling Xuei; Ying-Hua Cheng; Yun-Long Liu

    Sepsis is a dynamic state that progresses at variable rates and has life-threatening consequences. Staging patients along the sepsis timeline requires a thorough knowledge of the evolution of cellular and molecular events at the tissue level. Here, we investigated the kidney, an organ central to the pathophysiology of sepsis. Single-cell RNA-sequencing in a murine endotoxemia model revealed the involvement

    更新日期:2021-01-15
  • Evolutionary conflicts and adverse effects of antiviral factors
    eLife (IF 7.08) Pub Date : 2021-01-15
    Daniel Sauter; Frank Kirchhoff

    Human cells are equipped with a plethora of antiviral proteins protecting them against invading viral pathogens. In contrast to apoptotic or pyroptotic cell death, which serves as ultima ratio to combat viral infections, these cell-intrinsic restriction factors may prevent or at least slow down viral spread while allowing the host cell to survive. Nevertheless, their antiviral activity may also have

    更新日期:2021-01-15
  • An interbacterial DNA deaminase toxin directly mutagenizes surviving target populations
    eLife (IF 7.08) Pub Date : 2021-01-15
    Dean Huang; Dustin E Bosch; FoSheng Hsu; Hannah E Ledvina; Jacob P Frick; Joseph D Mougous; Jun Zeng; Marcos H de Moraes; Matthew C Radey; Noah Simon; Paul A Wiggins; S Brook Peterson

    When bacterial cells come in contact, antagonism mediated by the delivery of toxins frequently ensues. The potential for such encounters to have long-term beneficial consequences in recipient cells has not been investigated. Here we examined the effects of intoxication by DddA, a cytosine deaminase delivered via the type VI secretion system (T6SS) of Burkholderia cenocepacia. Despite its killing potential

    更新日期:2021-01-15
  • Identification of distinct pH-and zeaxanthin-dependent quenching in LHCSR3 from Chlamydomonas reinhardtii
    eLife (IF 7.08) Pub Date : 2021-01-15
    EonSeon Jin; Federico Perozeni; Gabriela S Schlau-Cohen; Julianne M Troiano; Kwangyrul Baek; Luca Zuliani; Matteo Ballottari; Raymundo Moya; Stefano Cazzaniga

    Under high light, oxygenic photosynthetic organisms avoid photodamage by thermally dissipating absorbed energy, which is called non-photochemical quenching. In green algae, a chlorophyll and carotenoid-binding protein, light-harvesting complex stress-related (LHCSR3), detects excess energy via a pH drop and serves as a quenching site. Using a combined in vivo and in vitro approach, we investigated

    更新日期:2021-01-15
  • Oxytocin modulates human chemosensory decoding of sex in a dose-dependent manner
    eLife (IF 7.08) Pub Date : 2021-01-13
    Kepu Chen; Nikolaus F Troje; Wen Zhou; Yuting Ye

    There has been accumulating evidence of human social chemo-signaling, but the underlying mechanisms remain poorly understood. Considering the evolutionarily conserved roles of oxytocin and vasopressin in reproductive and social behaviors, we examined whether the two neuropeptides are involved in the subconscious processing of androsta-4,16,-dien-3-one and estra-1,3,5 (10),16-tetraen-3-ol, two human

    更新日期:2021-01-14
  • Reproducible analysis of disease space via principal components using the novel R package syndRomics
    eLife (IF 7.08) Pub Date : 2021-01-14
    Abel Torres Espín; Adam Ferguson; Austin Chou; Nikolaos Kyritsis; Pavan S Upadhyayula; Russell Huie

    Biomedical data are usually analyzed at the univariate level, focused on a single primary outcome measure to provide insight into systems biology, complex disease states, and precision medicine opportunities. More broadly, these complex biological and disease states can be detected as common factors emerging from the relationships among measured variables using multivariate approaches. 'Syndromics'

    更新日期:2021-01-14
  • Temperature-dependent fasciation mutants provide a link between mitochondrial RNA processing and lateral root morphogenesis
    eLife (IF 7.08) Pub Date : 2021-01-14
    Akihito Mamiya; Atsuko Kinoshita; Hiroaki Tamaki; Kayoko Yamamoto; Ko Noguchi; Kurataka Otsuka; Mamoru Nozaki; Masaki Arita; Masato Saito; Mineko Konishi; Munetaka Sugiyama; Takahiro Nakamura; Takashi Hirayama; Takashi Ueda; Takehito Kobayashi; Takushi Hachiya; Yasushi Sato; Yusuke Yagi

    Although mechanisms that activate organogenesis in plants are well established, much less is known about the subsequent fine-tuning of cell proliferation, which is crucial for creating properly structured and sized organs. Here we show, through analysis of temperature-dependent fasciation (TDF) mutants of Arabidopsis, root redifferentiation defective 1 (rrd1), rrd2, and root initiation defective 4

    更新日期:2021-01-14
  • A mechanistic model for long-term immunological outcomes in South African HIV-infected children and adults receiving ART
    eLife (IF 7.08) Pub Date : 2021-01-14
    Eva Liliane Ujeneza; Geoffrey Fatti; Julien Riou; Martin Nieuwoudt; Mary-Ann Davies; Shobna Shawry; Wilfred Ndifon

    Long-term effects of the growing population of HIV-treated people in Southern Africa on individuals and the public health sector at large are not yet understood. This study proposes a novel 'ratio' model that relates CD4+ T-cell counts of HIV-infected individuals to the CD4+ count reference values from healthy populations. We use mixed-effects regression to fit the model to data from 1,616 children

    更新日期:2021-01-14
  • Brain functional networks associated with social bonding in monogamous voles
    eLife (IF 7.08) Pub Date : 2021-01-14
    Francisco J Camacho; Juan J Ortiz; Larry J Young; María Fernanda López-Gutiérrez; Nestor F Diaz; Raúl G Paredes; Sarael Alcauter; Wendy Portillo; Zeus Gracia-Tabuenca

    Previous studies have related pair bonding in Microtus ochrogaster, the prairie vole, with plastic changes in several brain regions. However, the interactions between these socially-relevant regions have yet to be described. In this study, we used resting state magnetic resonance imaging to explore bonding behaviors and functional connectivity of brain regions previously associated with pair bonding

    更新日期:2021-01-14
  • Cytokine ranking via mutual information algorithm correlates cytokine profiles with presenting disease severity in patients infected with SARS-CoV-2
    eLife (IF 7.08) Pub Date : 2021-01-14
    Anna D Louie; Chun Geun Lee; Eric A Ross; Jack A Elias; Kelsey E Huntington; Wafik S El-Deiry

    Although the range of immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is variable, cytokine storm is observed in a subset of symptomatic individuals. To further understand the disease pathogenesis and, consequently, to develop an additional tool for clinicians to evaluate patients for presumptive intervention we sought to compare plasma cytokine levels between a range

    更新日期:2021-01-14
  • Stable transplantation of human mitochondrial DNA by high-throughput, pressurized isolated mitochondrial delivery
    eLife (IF 7.08) Pub Date : 2021-01-13
    Alexander J Sercel; Alexander N Patananan; Amy K Yu; Garret W Guyot; Kayvan R Niazi; Michael A Teitell; Pei-Yu Chiou; Shahrooz Rabizadeh; Tianxing Man; Ting-Hsiang Wu

    Generating mammalian cells with specific mtDNA-nDNA combinations is desirable but difficult to achieve and would be enabling for studies of mitochondrial-nuclear communication and coordination in controlling cell fates and functions. We developed 'MitoPunch', a pressure-driven mitochondrial transfer device, to deliver isolated mitochondria into numerous target mammalian cells simultaneously. MitoPunch

    更新日期:2021-01-13
  • A transcriptomic taxonomy of Drosophila circadian neurons around the clock
    eLife (IF 7.08) Pub Date : 2021-01-13
    Dariusz Przybylski; Dingbang Ma; Katharine C Abruzzi; Matthias Schlichting; Michael Rosbash; Qunlong Li; Xi Long

    Many different functions are regulated by circadian rhythms, including those orchestrated by discrete clock neurons within animal brains. To comprehensively characterize and assign cell identity to the 75 pairs of Drosophila circadian neurons, we optimized a single cell RNA sequencing method and assayed clock neuron gene expression at different times of day. The data identify at least 17 clock neuron

    更新日期:2021-01-13
  • ARL3 activation requires the co-GEF BART and effector-mediated turnover
    eLife (IF 7.08) Pub Date : 2021-01-13
    Begoña Sot; Esther Garcia; Michael J McIlwraith; Shehab Ismail; Tamas Yelland; Yasmin ElMaghloob

    The ADP-ribosylation factor-like 3 (ARL3) is a ciliopathy G-protein which regulates the ciliary trafficking of several lipid-modified proteins. ARL3 is activated by its guanine exchange factor (GEF) ARL13B via an unresolved mechanism. BART is described as an ARL3 effector which has also been implicated in ciliopathies, although the role of its ARL3 interaction is unknown. Here we show that, at physiological

    更新日期:2021-01-13
  • High-resolution mapping of the neutralizing and binding specificities of polyclonal sera post HIV Env trimer vaccination
    eLife (IF 7.08) Pub Date : 2021-01-13
    Adam S Dingens; Andrew B Ward; Christopher A Cottrell; Jesse D Bloom; John P Moore; Julie M Overbaugh; Keara D Malone; Payal Pratap; P J Klasse; Sarah K Hilton; Thomas Ketas

    Mapping polyclonal serum responses is critical to rational vaccine design. However, most high-resolution mapping approaches involve isolating and characterizing individual antibodies, which incompletely defines the polyclonal response. Here we use two complementary approaches to directly map the specificities of the neutralizing and binding antibodies of polyclonal anti-HIV-1 sera from rabbits immunized

    更新日期:2021-01-13
  • Thymic stromal lymphopoietin limits primary and recall CD8+ T-cell anti-viral responses
    eLife (IF 7.08) Pub Date : 2021-01-13
    Daniel Gromer; Dorian B McGavern; Erin E West; Jangsuk Oh; Majid Kazemian; Ning Du; Peng Li; Phillip Swanson; Risa Ebina-Shibuya; Rosanne Spolski; Warren J Leonard

    Thymic stromal lymphopoietin (TSLP) is a cytokine that acts directly on CD4+ T cells and dendritic cells to promote progression of asthma, atopic dermatitis, and allergic inflammation. However, a direct role for TSLP in CD8+ T-cell primary responses remains controversial and its role in memory CD8+ T cell responses to secondary viral infection is unknown. Here, we investigate the role of TSLP in both

    更新日期:2021-01-13
  • MITF reprograms the extracellular matrix and focal adhesion in melanoma
    eLife (IF 7.08) Pub Date : 2021-01-13
    Berglind Ósk Einarsdottir; Colin Kenny; E Elizabeth Patton; Eirikur Steingrimsson; Erna Magnúsdóttir; Ilse Gerritsen; Jana Travnickova; Katrin Möller; Kritika Kirty; Lionel Larue; Margrét Helga Ögmundsdóttir; Marie de Tayrac; Mitchell Levesque; Ossia Margarita Eichhoff; Phil F Cheng; Philipp Cerny; Ramile Dilshat; Robert A Cornell; Romain Maurice Jacques Lasseur; Sara Sigurbjörnsdóttir; Valerie Fock

    The microphthalmia associated transcription factor (MITF) is a critical regulator of melanocyte development and differentiation. It also plays an important role in melanoma where it has been described as a molecular rheostat that, depending on activity levels, allows reversible switching between different cellular states. Here we show that MITF directly represses the expression of genes associated

    更新日期:2021-01-13
  • A retrospective analysis of the peer review of more than 75,000 Marie Curie proposals between 2007 and 2018
    eLife (IF 7.08) Pub Date : 2021-01-13
    Ana Marušić; Darko Hren; David G Pina; Ivan Buljan

    Most funding agencies rely on peer review to evaluate grant applications and proposals, but research into the use of this process by funding agencies has been limited. Here we explore if two changes to the organization of peer review for proposals submitted to various funding actions by the European Union has an influence on the outcome of the peer review process. Based on an analysis of more than

    更新日期:2021-01-13