34,435 results on '"biology"'
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102. Memories Are Made of This.
- Author
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Fox, Jeffrey L.
- Abstract
Provides comments on research studies related to memory systems, considering those exploring the nature of memory traces. One researcher suggests that memory trace circuits are extremely localized (as opposed to being diffuse), such that a lesion in a rabbit's brain can completely destroy the trace for a particular learned response. (JN)
- Published
- 1983
103. MCAT to Stress Thinking, Writing.
- Author
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Holden, Constance
- Abstract
Cites changes to occur on the Medical College Admissions Test to include: a reduction from six to four sections, biology and physics content-specific sections to absorb chemistry, elimination of multiple-choice questions to a problem-solving format, and the inclusion of graded essay questions. (RT)
- Published
- 1989
104. New Creationism Bill Already Drafted.
- Author
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Lewin, Roger
- Abstract
Reviews the major points of the American Civil Liberties Union (ACLU) challenge to the Arkansas bill "Unbiased Presentation of Creation Science and Evolution Science Bill." (SK)
- Published
- 1981
105. Who's Who in Biology.
- Author
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Norman, Colin
- Abstract
Provides top-rated programs (by university) in biochemistry, botany, cellular/molecular biology, microbiology, physiology, and zoology. Overall scores included with each program were obtained from 1,848 biologists who were asked to rate programs in terms of faculty quality and their effectiveness in educating graduate students. (Author/JN)
- Published
- 1983
106. A Blind Spot in Biology
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Epstein, Emanuel
- Abstract
Laments the neglect of discussion of active transport of plant nutrients from soil to root in general biology textbooks. (AL)
- Published
- 1972
107. World Ethics Body Proposed
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Holden, Constance
- Abstract
Outlines the main features and areas of responsibility of an international, non-governmental body proposed by the Council for International Organizations of Medical Sciences to explore the moral and social issues raised by recent and impending developments in biology and medicine. (AL)
- Published
- 1972
108. Two Cooks for the Same Kitchen?
- Author
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Bevan, William
- Abstract
Considers the implications of the apparently impending California requirement that all science textbooks to be considered for adoption include a serious treatment of creation theory. (AL)
- Published
- 1972
109. Learning biology to understand longevity.
- Author
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Brenner, Charles
- Subjects
- *
LONGEVITY , *BIOLOGY , *SOMATOTROPIN receptors , *MOLECULAR biology - Published
- 2024
- Full Text
- View/download PDF
110. RESEARCH.
- Author
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M. N., L. M. Z., J. S., J. S. Y., D. J., K. T. S., V. V., R. D., Y .Y., Y. N., P. N. K., Y. S., and B. W.
- Subjects
- *
BIODIVERSITY , *NATURE , *BIOLOGY , *SCIENCE , *GENOMES - Abstract
The article discusses about Genetic modifications of organisms can create artificial, synthetic genomes. Such changes are forecast to be useful for understanding the principles of how genomic context affects cellular function. However, the effects of most drastic genomic movements are unknown, never having been observed in nature. Brooks et al. examined a line of yeast that are easily induced to move genes within the genome.
- Published
- 2022
111. Evolution and antiviral activity of a human protein of retroviral origin
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John A. Frank, Manvendra Singh, Harrison B. Cullen, Raphael A. Kirou, Meriem Benkaddour-Boumzaouad, Jose L. Cortes, Jose Garcia Pérez, Carolyn B. Coyne, and Cédric Feschotte
- Subjects
Genetics ,Natural selection ,Multidisciplinary ,biology ,Zoonotic Infection ,Genome, Human ,Placenta ,Gene Products, env ,Genomics ,Pregnancy Proteins ,biology.organism_classification ,Genome ,Betaretrovirus ,Placentation ,Transcriptome ,Evolution, Molecular ,Retrovirus ,Pregnancy ,Animals ,Humans ,Human genome ,Female ,Gene - Abstract
Summary Viruses circulating in wild and domestic animals pose a constant threat to human health1. Identifying human genetic factors that protect against zoonotic infections is a health priority. The RD-114 and Type-D retrovirus (RDR) interference group includes infectious viruses that circulate in domestic cats and various Old World monkeys (OWM), and utilize ASCT2 as a common target cell receptor2. While human ASCT2 can mediate RDR infection in cell culture, it is unknown whether humans and other hominoids encode factors that restrict RDR infection in nature2,3. Here we test the hypothesis that Suppressyn, a truncated envelope protein that binds ASCT2 and is derived from a human endogenous retrovirus4,5, restricts RDR infection. Transcriptomics and regulatory genomics reveal that Suppressyn expression initiates in the preimplantation embryo. Loss and gain of function experiments in cell culture show Suppressyn expression is necessary and sufficient to restrict RDR infection. Evolutionary analyses show Suppressyn was acquired in the genome of a common ancestor of hominoids and OWMs, but preserved by natural selection only in hominoids. Restriction assays using modern primate orthologs and reconstructed ancestral genes indicate that Suppressyn antiviral activity has been conserved in hominoids, but lost in most OWM. Thus in humans and other hominoids, Suppressyn acts as a restriction factor against retroviruses with zoonotic capacity. Transcriptomics data predict that other virus-derived proteins with potential antiviral activity lay hidden in the human genome.
- Published
- 2022
112. A keystone gene underlies the persistence of an experimental food web
- Author
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Barbour, Matthew A, Kliebenstein, Daniel J, Bascompte, Jordi, and University of Zurich
- Subjects
Food Chain ,Insecta ,Multidisciplinary ,Arabidopsis Proteins ,UFSP13-8 Global Change and Biodiversity ,Arabidopsis ,Genes, Plant ,Evolution, Molecular ,10127 Institute of Evolutionary Biology and Environmental Studies ,Gene Frequency ,Loss of Function Mutation ,Animals ,570 Life sciences ,biology ,590 Animals (Zoology) ,Herbivory - Abstract
Genes encode information that determines an organism’s fitness. Yet we know little about whether genes of one species influence the persistence of interacting species in an ecological community. Here, we experimentally tested the effect of three plant defense genes on the persistence of an insect food web and found that a single allele at a single gene promoted coexistence by increasing plant growth rate, which in turn increased the intrinsic growth rates of species across multiple trophic levels. Our discovery of a “keystone gene” illustrates the need to bridge between biological scales, from genes to ecosystems, to understand community persistence.
- Published
- 2022
113. Multiple causal variants underlie genetic associations in humans
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Nathan S. Abell, Stephen B. Montgomery, Emily Greenwald, Kevin S. Smith, Michael J. Gloudemans, Marianne K. DeGorter, and Zihuai S He
- Subjects
Linkage disequilibrium ,Multifactorial Inheritance ,Multiple Sclerosis ,Quantitative Trait Loci ,Disease ,Quantitative trait locus ,Biology ,Linkage Disequilibrium ,Untranslated Regions ,Genetic variation ,Humans ,Genetic Predisposition to Disease ,Allele ,Alleles ,Genetics ,Multidisciplinary ,Genome, Human ,Platelet Count ,Genetic Variation ,Inflammatory Bowel Diseases ,Asthma ,Chromatin ,Histone Code ,Phenotype ,Haplotypes ,Expression quantitative trait loci ,Trait ,Genome-Wide Association Study ,Transcription Factors - Abstract
The majority of associations between genetic variation and human traits and diseases are non-coding and in strong linkage disequilibrium (LD) with surrounding genetic variation. In these cases, a single causal variant is often assumed to underlie the association, however no systematic assessment of the number of causal variants has been performed. In this study, we applied a massively parallel reporter assay (MPRA) in lymphoblastoid cells to functionally evaluate 49,256 allelic pairs, representing 30,893 genetic variants in high, local linkage disequilibrium for 744 independent cis-expression quantitative trait loci (eQTL) and assessed each for colocalization across 114 traits. We identified 8,502 allele-independent regulatory regions containing 1,264 allele-specific regulatory variants, and found that 17.7% of eQTL contained more than one significant allelic effect. We show that detected regulatory variants are highly and specifically enriched for activating chromatin structures and allelic transcription factor binding, for which ETS-domain family members are a large driver. Integration of MPRA profiles with eQTL/complex trait colocalizations identified causal variant sets for associations with blood cell measurements, Asthma, Multiple Sclerosis, Inflammatory Bowel Disease, and Crohn’s Disease. These results demonstrate that a sizable number of association signals are manifest through multiple, tightly-linked causal variants requiring high-throughput functional assays for fine-mapping.
- Published
- 2022
114. Bacterial gasdermins reveal an ancient mechanism of cell death
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Yaara Oppenheimer-Shaanan, Tanita Wein, Megan L. Mayer, Erez Yirmiya, Alex G. Johnson, Rotem Sorek, Philip J. Kranzusch, Brianna Duncan-Lowey, and Gil Amitai
- Subjects
Models, Molecular ,Protein Conformation, alpha-Helical ,Programmed cell death ,Proteases ,Protein Conformation ,Cytophagaceae ,Cleavage (embryo) ,Crystallography, X-Ray ,Article ,Immune system ,Bacterial Proteins ,Protein Domains ,medicine ,Pyroptosis ,Bacteriophages ,Bradyrhizobium ,Myxococcales ,Multidisciplinary ,biology ,Bacteria ,Chemistry ,Cell Membrane ,Eukaryota ,Inflammasome ,biology.organism_classification ,Peptide Fragments ,Cell biology ,Neoplasm Proteins ,Lytic cycle ,Lipid modification ,Apoptosis Regulatory Proteins ,medicine.drug ,Peptide Hydrolases - Abstract
Gasdermin proteins form large membrane pores in human cells that release immune cytokines and induce lytic cell death. Gasdermin pore formation is triggered by caspase-mediated cleavage during inflammasome signaling and is critical for defense against pathogens and cancer. Here we discover gasdermin homologs encoded in bacteria that execute prokaryotic cell death. Structures of bacterial gasdermins reveal a conserved pore-forming domain that is stabilized in the inactive state with a buried lipid modification. We demonstrate that bacterial gasdermins are activated by dedicated caspase-like proteases that catalyze site-specific cleavage and removal of an inhibitory C-terminal peptide. Release of autoinhibition induces the assembly of >200 Å pores that form a mesh-like structure and disrupt membrane integrity. These results demonstrate that caspase-mediated activation of gasdermins is an ancient form of regulated cell death shared between bacteria and animals.
- Published
- 2022
115. Rapid assessment of SARS-CoV-2–evolved variants using virus-like particles
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Abdullah M. Syed, Irene P. Chen, Jennifer M. Hayashi, Mir M. Khalid, Katarzyna M. Soczek, Jennifer A. Doudna, Taha Y. Taha, Melanie Ott, Alison Ciling, Takako Tabata, Bharath Sreekumar, and Pei-Yi Chen
- Subjects
2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,viruses ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Genome, Viral ,Biology ,Virus ,Cell Line ,Evolution, Molecular ,Viral Matrix Proteins ,Coronavirus Envelope Proteins ,Animals ,Coronavirus Nucleocapsid Proteins ,Humans ,RNA, Messenger ,Multidisciplinary ,SARS-CoV-2 ,Viral Genome Packaging ,Virus Internalization ,Phosphoproteins ,Virology ,Rapid assessment ,Mutation ,Spike Glycoprotein, Coronavirus ,Artificial Virus-Like Particles ,Spike (software development) ,Plasmids - Abstract
A tool to probe SARS-CoV-2 biology To develop therapies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and emerging variants, it is important to understand the viral biology and the effect of mutations. However, this is challenging because live virus can only be studied in a few laboratories that meet stringent safety standards. Syed et al . describe a virus-like particle (VLP) that comprises the four SARS-CoV-2 structural proteins, but instead of packaging viral RNA, it packages messenger RNA (mRNA) that expresses a reporter protein (see the Perspective by Johnson and Menachery). The amount of reporter expressed in receiver cells depends on the efficiency of packaging and assembly in the producer cells and the efficiency of entry into receiver cells. Mutations in the nucleocapsid protein that are found in more transmissible variants increase mRNA packaging and expression. The VLPs provide a platform for studying the effect of mutations in the structural proteins and for screening therapeutics. —VV
- Published
- 2021
116. Membrane fusion and immune evasion by the spike protein of SARS-CoV-2 Delta variant
- Author
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Pei Tong, Yongfei Cai, Avneesh Gautam, Bing Chen, Sophia Rits-Volloch, Jun Zhang, Megan L. Mayer, Duane R. Wesemann, Wei Yang, Haisun Zhu, Michael S. Seaman, Christy L. Lavine, Hanqin Peng, Richard M. Walsh, Jianming Lu, Krishna Anand, and Tianshu Xiao
- Subjects
Models, Molecular ,Delta ,Antigenicity ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Protein Conformation ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Antibody Affinity ,Alpha (ethology) ,Biology ,Antibodies, Viral ,Membrane Fusion ,Article ,In Brief ,Cell Line ,Epitopes ,Immune system ,Protein Domains ,Antigen ,Humans ,Beta (finance) ,Antigens, Viral ,Immune Evasion ,Multidisciplinary ,SARS-CoV-2 ,Lipid bilayer fusion ,Spike Protein ,Evasion (ethics) ,Virology ,Mutation ,Spike Glycoprotein, Coronavirus ,biology.protein ,Angiotensin-Converting Enzyme 2 ,Protein Multimerization ,Antibody ,Function (biology) ,Receptors, Coronavirus - Abstract
Delta’s spike Understanding the molecular mechanisms of the increased transmissibility and immune evasion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is critical to guiding current and future intervention strategies. Zhang et al . determined cryo–electron microscopy structures of the full-length spike protein trimers of the Delta, Kappa, and Gamma variants of SARS-CoV-2 and studied their function and antigenic properties. The Delta spike protein fused membranes more efficiently at low levels of the cellular receptor ACE2, and its pseudotyped viruses infected target cells substantially more rapidly than all other variants tested, possibly at least partly accounting for its heightened transmissibility. Mutations of each variant rearranged the antigenic surface of the N-terminal domain of the spike protein but only caused local changes in the receptor-binding domain, consistent with greater resistance to neutralizing antibodies. These findings elucidate the molecular events that have led these viruses to adapt in human communities and to evade host immunity. —VV
- Published
- 2021
117. Ground tissue circuitry regulates organ complexity in maize and Setaria
- Author
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Carlos Ortiz-Ramírez, Ramin Rahni, Sanqiang Zhang, Kenneth D. Birnbaum, Thomas R. Gingeras, Laura Lee, Bruno Guillotin, Poliana Coqueiro Dias Araujo, Zhe Yan, Edgar Demesa-Arevalo, Joyce Van Eck, David A. Jackson, Xiaosa Xu, and Kimberly L. Gallagher
- Subjects
Setaria ,Multidisciplinary ,Transcription, Genetic ,Plant roots ,Setaria Plant ,food and beverages ,Biology ,Flow Cytometry ,biology.organism_classification ,Plant Roots ,Zea mays ,Article ,Ground tissue ,medicine.anatomical_structure ,Symbiosis ,Cortex (anatomy) ,Botany ,medicine ,RNA-Seq ,Single-Cell Analysis ,Genome, Plant ,Plant Proteins ,Transcription Factors - Abstract
Most plant roots have multiple cortex layers that make up the bulk of the organ and play key roles in physiology, such as flood tolerance and symbiosis. However, little is known about the formation of cortical layers outside of the highly reduced anatomy of Arabidopsis. Here we use single-cell RNAseq to rapidly generate a cell resolution map of the maize root, revealing an alternative configuration of the tissue formative transcription factor SHORT-ROOT (SHR) adjacent to an expanded cortex. We show that maize SHR protein is hypermobile, moving at least eight cell layers into the cortex. Higher-order SHR mutants in both maize and Setaria have reduced numbers of cortical layers, showing that the SHR pathway controls expansion of cortical tissue to elaborate anatomical complexity.
- Published
- 2021
118. Error-prone, stress-induced 3′ flap–based Okazaki fragment maturation supports cell survival
- Author
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Amanpreet Singh, Judith L. Campbell, Jinhui Wang, Li Zheng, Zhaohui Gu, Xiwei Wu, Binghui Shen, Zhaoning Lu, Mian Zhou, Haitao Sun, Yajing Zhou, Eric Zheng, and Zunsong Hu
- Subjects
DNA Replication ,Saccharomyces cerevisiae Proteins ,Multidisciplinary ,Okazaki fragments ,Cell Survival ,Flap Endonucleases ,Stress induced ,Temperature ,DNA replication ,Cell Cycle Proteins ,DNA ,Saccharomyces cerevisiae ,Protein Serine-Threonine Kinases ,Biology ,Environmental stress ,Article ,Cell biology ,Stress, Physiological ,Apoptosis ,Nucleic Acid Conformation ,DNA, Fungal ,Cell survival ,DNA Polymerase III ,Signal Transduction - Abstract
How cells with DNA replication defects acquire mutations that allow them to escape apoptosis under environmental stress is a long-standing question. Here, we report that an error-prone Okazaki fragment maturation (OFM) pathway is activated at restrictive temperatures in rad27Δ yeast cells. Restrictive temperature stress activated Dun1, facilitating transformation of unprocessed 5′ flaps into 3′ flaps, which were removed by 3′ nucleases, including DNA polymerase δ (Polδ). However, at certain regions, 3′ flaps formed secondary structures that facilitated 3′ end extension rather than degradation, producing alternative duplications with short spacer sequences, such as pol3 internal tandem duplications. Consequently, little 5′ flap was formed, suppressing rad27Δ-induced lethality at restrictive temperatures. We define a stress-induced, error-prone OFM pathway that generates mutations that counteract replication defects and drive cellular evolution and survival.
- Published
- 2021
119. Genetic ancestry effects on the response to viral infection are pervasive but cell type specific
- Author
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Beth K Thielen, Jessica K. Fiege, Mari Shiratori, Clayton K. Mickelson, Ryan A. Langlois, Luis B. Barreiro, João Barroso-Batista, and Haley E. Randolph
- Subjects
Genetics ,Titer ,Multidisciplinary ,Immune system ,Infectious disease (medical specialty) ,Interferon ,Genetic genealogy ,medicine ,Quantitative trait locus ,Biology ,Gene ,Peripheral blood mononuclear cell ,medicine.drug - Abstract
Humans differ in their susceptibility to infectious disease, partly owing to variation in the immune response after infection. We used single-cell RNA sequencing to quantify variation in the response to influenza infection in peripheral blood mononuclear cells from European- and African-ancestry males. Genetic ancestry effects are common but highly cell type specific. Higher levels of European ancestry are associated with increased type I interferon pathway activity in early infection, which predicts reduced viral titers at later time points. Substantial population-associated variation is explained by cis-expression quantitative trait loci that are differentiated by genetic ancestry. Furthermore, genetic ancestryÐassociated genes are enriched among genes correlated with COVID-19 disease severity, suggesting that the early immune response contributes to ancestry-associated differences for multiple viral infection outcomes. [ FROM AUTHOR] Copyright of Science is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)
- Published
- 2021
120. Mechanism of siRNA production by a plant Dicer-RNA complex in dicing-competent conformation
- Author
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Laixing Zhang, Steven E. Jacobsen, Jiamu Du, Zhe Wu, C. Jake Harris, Sisi Li, Zhenhui Zhong, Qian Wang, Maojun Yang, Changshi Wang, Zhenlin Yang, Suhua Feng, Jixian Zhai, Yan Xue, and Lifan Xiao
- Subjects
Models, Molecular ,Ribonuclease III ,Protein Conformation ,Arabidopsis ,Article ,Protein Domains ,Phosphorylation ,RNA, Small Interfering ,Multidisciplinary ,biology ,Arabidopsis Proteins ,Chemistry ,Mechanism (biology) ,Cryoelectron Microscopy ,RNA ,Cell biology ,enzymes and coenzymes (carbohydrates) ,Mutagenesis ,RNA, Plant ,Transfer RNA ,biology.protein ,Nucleic Acid Conformation ,Wafer dicing ,Biogenesis ,Protein Binding ,Dicer - Abstract
In eukaryotes, small RNAs (sRNAs) play critical roles in multiple biological processes. Dicer endonucleases are a central part of sRNA biogenesis. In plants, DICER-LIKE PROTEIN 3 (DCL3) produces 24-nucleotide (nt) small interfering RNAs (siRNAs) that determine the specificity of the RNA-directed DNA methylation pathway. Here, we determined the structure of a DCL3–pre-siRNA complex in an active dicing-competent state. The 5′-phosphorylated A1 of the guide strand and the 1-nt 3′ overhang of the complementary strand are specifically recognized by a positively charged pocket and an aromatic cap, respectively. The 24-nt siRNA length dependence relies on the separation between the 5′-phosphorylated end of the guide RNA and dual cleavage sites formed by the paired ribonuclease III domains. These structural studies, complemented by functional data, provide insight into the dicing principle for Dicers in general.
- Published
- 2021
121. A viral RNA hijacks host machinery using dynamic conformational changes of a tRNA-like structure
- Author
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Madeline E. Sherlock, Jeffrey S. Kieft, Steve Bonilla, and Andrea MacFadden
- Subjects
Models, Molecular ,Phaseolus ,Multidisciplinary ,Protein Conformation ,Host (biology) ,Extramural ,viruses ,Cryoelectron Microscopy ,Molecular Mimicry ,food and beverages ,RNA ,Genome, Viral ,Computational biology ,Biology ,Virus Replication ,Bromovirus ,Article ,RNA, Transfer ,Tyrosine-tRNA Ligase ,Transfer RNA ,Nucleic Acid Conformation ,RNA, Viral ,Viral rna ,Transfer RNA Aminoacylation ,Protein Binding - Abstract
Viruses require multifunctional structured RNAs to hijack their host’s biochemistry, but their mechanisms can be obscured by the difficulty of solving conformationally dynamic RNA structures. Using cryo–electron microscopy (cryo-EM), we visualized the structure of the mysterious viral transfer RNA (tRNA)–like structure (TLS) from the brome mosaic virus, which affects replication, translation, and genome encapsidation. Structures in isolation and those bound to tyrosyl-tRNA synthetase (TyrRS) show that this ~55-kilodalton purported tRNA mimic undergoes large conformational rearrangements to bind TyrRS in a form that differs substantially from that of tRNA. Our study reveals how viral RNAs can use a combination of static and dynamic RNA structures to bind host machinery through highly noncanonical interactions, and we highlight the utility of cryo-EM for visualizing small, conformationally dynamic structured RNAs.
- Published
- 2021
122. Biosynthesis of fluopsin C, a copper-containing antibiotic from Pseudomonas aeruginosa
- Author
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R. David Britt, L. Henry Bryant, Lizhi Tao, Jon B. Patteson, Andrew T. Putz, William C. Simke, and Bo Li
- Subjects
Multidisciplinary ,biology ,Chemistry ,medicine.drug_class ,Pseudomonas aeruginosa ,Pseudomonas ,Antibiotics ,chemistry.chemical_element ,biology.organism_classification ,medicine.disease_cause ,Copper ,Microbiology ,Fight-or-flight response ,chemistry.chemical_compound ,Biosynthesis ,Bacterial virulence ,medicine - Abstract
A copper-containing antibiotic Bacteria require transition metal ions for biological processes and must also protect themselves against excess metal, which is toxic. Patteson et al . explored how the environmental bacterium Pseudomonas aeruginosa uses a five-enzyme pathway to synthesize a small-molecule complex, fluopsin C, which is built from cysteine and contains a copper ion. The biosynthesis involves unusual enzymatic transformations that convert cysteine to a thiohydroximate, two of which chelate a copper ion in the final natural product. Fluopsin C protects P. aeruginosa from excess copper and also acts as a broad-spectrum antibiotic against other bacteria. —VV
- Published
- 2021
123. Structural basis of Integrator-mediated transcription regulation
- Author
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Christian Dienemann, Isaac Fianu, Olexandr Dybkov, Henning Urlaub, Ying Chen, Patrick Cramer, and Andreas Linden
- Subjects
Models, Molecular ,Transcription, Genetic ,Protein Conformation ,RNA polymerase II ,03 medical and health sciences ,0302 clinical medicine ,Protein Domains ,Transcription (biology) ,Endoribonucleases ,Transcriptional regulation ,Humans ,Protein Phosphatase 2 ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,biology ,Chemistry ,Cryoelectron Microscopy ,RNA ,Protein phosphatase 2 ,Cell biology ,DNA-Binding Proteins ,Protein Subunits ,Gene Expression Regulation ,Multiprotein Complexes ,Integrator ,biology.protein ,RNA Polymerase II ,030217 neurology & neurosurgery ,Protein Binding - Abstract
Integrator and protein phosphatase 2A (PP2A) form a complex that dephosphorylates paused RNA polymerase II (Pol II), cleaves the nascent RNA, and terminates transcription. We report the structure of the pretermination complex containing the human Integrator-PP2A complex bound to paused Pol II. Integrator binds Pol II and the pausing factors DSIF and NELF to exclude binding of the elongation factors SPT6 and PAF1 complex. Integrator also binds the C-terminal domain of Pol II and positions PP2A to counteract Pol II phosphorylation and elongation. The Integrator endonuclease docks to the RNA exit site and opens to cleave nascent RNA about 20 nucleotides from the Pol II active site. Integrator does not bind the DNA clamps formed by Pol II and DSIF, enabling release of DNA and transcription termination.
- Published
- 2021
124. CD4 + T cells contribute to neurodegeneration in Lewy body dementia
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Douglas Galasko, Hamilton Oh, Andreas Keller, Tobias Fehlmann, Tony Wyss-Coray, Kathleen L. Poston, Michael S. Unger, Emma Tapp, David Gate, Tim J. Nonninger, Katharina Strempfl, Divya Channappa, Victor W. Henderson, Andrew C. Yang, Ludwig Aigner, Olivia Leventhal, Mark M. Davis, and Marian Shahid
- Subjects
Multidisciplinary ,Lewy body ,Mechanism (biology) ,T cell ,Neurodegeneration ,Biology ,medicine.disease ,Acquired immune system ,medicine.anatomical_structure ,medicine ,Dementia ,Neuroscience ,hormones, hormone substitutes, and hormone antagonists ,Homing (hematopoietic) - Abstract
Autoimmunity in Lewy body dementia Lewy body dementia (LBD) is a brain disease that leads to progressive decline in thinking, movement, and independent function. It results from the build-up of microscopic deposits called Lewy bodies, which develop from the aggregation of a misfolded protein called α-synuclein. Gate et al . observed immune cells known as T cells in the brains of LBD patients (see the Perspective by Krot and Rolls). Genomics analysis revealed that T cells traffic to the LBD brain and are associated with neuronal damage. When stimulated with α-synuclein, LBD patient T cells secrete an inflammatory protein known to damage neurons. These findings suggest an unexpected detrimental role of the immune system in LBD. —SMH
- Published
- 2021
125. Stepwise synaptic plasticity events drive the early phase of memory consolidation
- Author
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Yasunori Hayashi, Masanori Murayama, Suzune Tsukamoto, Akihiro Goto, Thomas J. McHugh, Ayaka Bota, Daichi Hirai, Tomoki Matsuda, Takeharu Nagai, Ken Miya, Xinzhi Jiang, and Jingbo Wang
- Subjects
Male ,Long-Term Potentiation ,Hippocampus ,Mice, Transgenic ,Biology ,Optogenetics ,Mice ,Cortex (anatomy) ,Neuroplasticity ,medicine ,Animals ,CA1 Region, Hippocampal ,Memory Consolidation ,Neuronal Plasticity ,Multidisciplinary ,Pyramidal Cells ,Excitatory Postsynaptic Potentials ,Long-term potentiation ,Rats ,Mice, Inbred C57BL ,Chromophore-Assisted Light Inactivation ,medicine.anatomical_structure ,Synapses ,Synaptic plasticity ,Excitatory postsynaptic potential ,Memory consolidation ,Sleep ,Neuroscience - Abstract
Where and when of memory consolidation Episodic memory is initially encoded in the hippocampus and later transferred to other brain regions for long-term storage. Synaptic plasticity underlies learning and plays a critical role in memory consolidation. However, it remains largely unknown where and when synaptic plasticity occurs and how it shapes the neuronal representation. Goto et al . developed a new tool for controlling early structural long-term potentiation (sLTP). By selectively manipulating sLTP, the authors showed that the local circuitry in hippocampal area CA1 is required for memory formation shortly after the encoding event. The local circuitry is also important for offline memory consolidation within 24 hours. The anterior cingulate cortex, another brain region directly connected with area CA1, is crucial for memory consolidation during sleep on the second night. —PRS
- Published
- 2021
126. The glial framework reveals white matter fiber architecture in human and primate brains
- Author
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Aviv Mezer and Roey Schurr
- Subjects
Physics ,Multidisciplinary ,Staining and Labeling ,biology ,Resolution (electron density) ,Brain ,Macaca mulatta ,White Matter ,Axons ,Corpus Callosum ,White matter ,Diffusion Magnetic Resonance Imaging ,medicine.anatomical_structure ,nervous system ,biology.animal ,Chlorocebus aethiops ,Image Processing, Computer-Assisted ,medicine ,Animals ,Humans ,Fiber architecture ,Primate ,Neuroglia ,Neuroscience - Abstract
How to quantify local axonal orientations Mapping the axonal trajectories of the brain’s white matter at cellular resolution is a long-standing goal of neuroscience. However, existing methods for mapping the axons are either limited to animal studies or require highly specialized equipment for data acquisition and processing. Nissl staining identifies cell nuclei and has been used extensively to investigate parcellations of the cortical gray matter, but the white matter has largely been neglected with this technique. Schurr and Mezer now show that Nissl staining, together with structure tensor analysis, can be used to study white matter architecture and the organization of the glial cell framework around axons over the whole brain. This technique greatly advances our knowledge regarding the organization of glial cells and the fine-grained organization of axonal projections in the brain. —PRS
- Published
- 2021
127. Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis
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Serine Avagyan, Margaret C. Weber, Jung-Ki Yoon, Meeta Mistry, Jessica L Moore, Jonathan E. Henninger, Song P. Yang, Leonard I. Zon, and W. P. Mannherz
- Subjects
Mutant ,Inflammation ,Biology ,Nuclear Receptor Subfamily 4, Group A, Member 1 ,medicine ,Animals ,Myeloid Cells ,DNA (Cytosine-5-)-Methyltransferases ,RNA-Seq ,Selection, Genetic ,Progenitor cell ,Frameshift Mutation ,Zebrafish ,Multidisciplinary ,Clonal hematopoiesis ,Zebrafish Proteins ,Genes, p53 ,Hematopoietic Stem Cells ,Cell biology ,Repressor Proteins ,Haematopoiesis ,Mutation ,Cytokines ,CRISPR-Cas Systems ,Clonal Hematopoiesis ,Single-Cell Analysis ,medicine.symptom - Abstract
Colorful clones in the blood Stem cells in regenerating tissues such as the blood can acquire mutations that enable a growth advantage, increasing the chance of developing cancer. It is unclear how such diverse mutations promote clonal fitness. Avagyan et al . generated a platform in zebrafish to label clones with unique hues while inducing mutations in genes implicated in human blood disorders. Mutations in some genes caused clones to expand over time, resulting in clonal dominance. Progenitors in the dominant clone expressed anti-inflammatory factors to resist the inflammatory environment produced by their own mature progeny, leading to a self-perpetuating cycle promoting clonal fitness. Targeting these resistance pathways may be used to abate clonal hematopoiesis and prevent its associated pathology. —BAP
- Published
- 2021
128. The simplest of slumbers
- Author
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Elizabeth Pennisi
- Subjects
2019-20 coronavirus outbreak ,Multidisciplinary ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Biology ,Virology - Abstract
Evidence from evolutionarily ancient creatures is revealing that sleep is not just for the brain
- Published
- 2021
129. Processing of NODULE INCEPTION controls the transition to nitrogen fixation in root nodules
- Author
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Katharina Schiessl, Tak H. Lee, Jian Feng, and Giles E. D. Oldroyd
- Subjects
Multidisciplinary ,Root nodule ,chemistry ,Botany ,medicine ,Nitrogen fixation ,Master regulator ,chemistry.chemical_element ,Nodule (medicine) ,medicine.symptom ,Biology ,Nitrogen ,Legume - Abstract
Nodulation regulation Legumes convert atmospheric nitrogen into biologically useful ammonium with the help of symbiotic bacteria housed in root nodules. Much of nodule development is controlled by the transcription factor NODULE INCEPTION (NIN). Feng et al . show that NIN is proteolytically processed to release a fragment that regulates the later stages of nodulation when the nodules acquire nitrogen-fixing capability. In related work, Jiang et al . identified members of the NIN-like protein (NLP) transcription factor family as being regulators of leghemoglobin expression acting through an unusual promotor motif shared across legumes. —PJH
- Published
- 2021
130. NIN-like protein transcription factors regulate leghemoglobin genes in legume nodules
- Author
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Qiujiu Li, Kirankumar S. Mysore, Ping Xu, Suyu Jiang, Jiangqi Wen, Yiting Ruan, Ertao Wang, Yann Pecrix, Pascal Gamas, Carmen Sánchez-Cañizares, Marie-Françoise Jardinaud, Meijun Zhu, Jinpeng Gao, Fuyu Li, Phillip S. Poole, Jeremy D. Murray, Laboratoire des Interactions Plantes Microbes Environnement (LIPME), and Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
- Subjects
Fixation de l'azote ,0106 biological sciences ,Root nodule ,[SDV]Life Sciences [q-bio] ,nodosité racinaire ,Biology ,Plant Root Nodulation ,01 natural sciences ,F30 - Génétique et amélioration des plantes ,03 medical and health sciences ,Symbiosis ,Gene Expression Regulation, Plant ,Nitrogen Fixation ,Medicago truncatula ,Légumineuse ,Promoter Regions, Genetic ,Leghemoglobin ,Gene ,Transcription factor ,ComputingMilieux_MISCELLANEOUS ,Legume ,Plant Proteins ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,Léghémoglobine ,food and beverages ,Fabaceae ,Facteur de transcription ,Cell biology ,Oxygen ,Nitrogen fixation ,Root Nodules, Plant ,Transcription ,Transcription Factors ,010606 plant biology & botany - Abstract
Leghemoglobins enable the endosymbiotic fixation of molecular nitrogen (N2) in legume nodules by channeling O2 for bacterial respiration while maintaining a micro-oxic environment to protect O2-sensitive nitrogenase. We found that the NIN-like protein (NLP) transcription factors NLP2 and NIN directly activate the expression of leghemoglobins through a promoter motif, resembling a “double” version of the nitrate-responsive elements (NREs) targeted by other NLPs, that has conserved orientation and position across legumes. CRISPR knockout of the NRE-like element resulted in strongly decreased expression of the associated leghemoglobin. Our findings indicate that the origins of the NLP-leghemoglobin module for O2 buffering in nodules can be traced to an ancient pairing of NLPs with nonsymbiotic hemoglobins that function in hypoxia.
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- 2021
131. G 1 cyclin–Cdk promotes cell cycle entry through localized phosphorylation of RNA polymerase II
- Author
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Georgi K. Marinov, Matthew P. Swaffer, Jonathan J. Turner, Mardo Kõivomägi, and Jan M. Skotheim
- Subjects
Multidisciplinary ,biology ,Cell division ,Chemistry ,Kinase ,Cyclin-dependent kinase ,Transcription (biology) ,biology.protein ,Promoter ,RNA polymerase II ,Cell cycle ,Transcription factor ,Cell biology - Abstract
Control by RNA polymerase II Evidence indicates that yeast cells initiate DNA synthesis and transition from the G 1 to the S phase of the cell cycle when cyclin 3 accumulates and causes phosphorylation of Whi5, a functional equivalent of the mammalian Rb (retinoblastoma) protein. Kõivomägi et al . now present evidence for a different cyclin-dependent kinase target (see the Perspective by Fisher). They found that the cyclin 3–cyclin-dependent kinase (Cdk) 1 complex in yeast promoted phosphorylation of RNA polymerase II and thus increased transcription at genes that control entry into the cell cycle. Cdks that regulate the cell cycle can thus act by similar mechanisms to so-called “transcriptional Cdks,” which are known to act as transcriptional regulators but not to function in control of cell division. —LBR
- Published
- 2021
132. The widespread IS200/IS605 transposon family encodes diverse programmable RNA-guided endonucleases
- Author
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Suchita P. Nety, Feng Zhang, Eugene V. Koonin, William P. Inskeep, Kira S. Makarova, Mensur Dlakić, Rachel Oshiro, Han Altae-Tran, Rhiannon K. Macrae, Soumya Kannan, Luke J. McKay, and F. Esra Demircioglu
- Subjects
Genetics ,Transposable element ,Endonuclease ,Multidisciplinary ,biology ,Extramural ,Cas9 ,Genetic variation ,biology.protein ,RNA ,Genetic code ,Conserved sequence - Abstract
Tracing the origin of CRISPR-Cas CRISPR-Cas systems have transformed genome editing and other biotechnologies; however, the broader origins and diversity of RNA-guided nucleases have largely remained unexplored. Altae-Tran et al . show that three distinct transposon-encoded proteins, IscB, IsrB, and TnpB, are naturally occurring, reprogrammable RNA-guided DNA nucleases (see the Perspective by Rousset and Sorek). In addition to identifying diverse guide-encoding mechanisms, the authors elucidate the evolutionary relationship between IsrB, IscB, and CRISPR-Cas9. Overall, these newly characterized systems, called OMEGA (for obligate mobile element–guided activity) systems, are found in all domains of life and may be harnessed for biotechnology development. —DJ
- Published
- 2021
133. Insights into human history from the first decade of ancient human genomics
- Author
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Yichen Liu, Qiaomei Fu, Xiaowei Mao, and Johannes Krause
- Subjects
Asia ,Human Migration ,Oceania ,Population Dynamics ,Human genomics ,Genomics ,Computational biology ,Biology ,Genome ,DNA sequencing ,chemistry.chemical_compound ,Animals ,Humans ,DNA, Ancient ,History, Ancient ,Neanderthals ,Multidisciplinary ,Scope (project management) ,Genome, Human ,Historical Article ,Biological Evolution ,Europe ,Siberia ,Ancient DNA ,chemistry ,Africa ,Americas ,DNA - Abstract
Recent advancements in DNA sequencing technologies and laboratory preparation protocols have rapidly expanded the scope of ancient DNA research over the past decade, both temporally and geographically. Discoveries include interactions between archaic and modern humans as well as modern human population dynamics, including those coinciding with the Last Glacial Maximum and the settlement history of most world regions. This new type of data allows us to examine the deep past of human population dynamics and sharpen the current understanding of our present. The continued development in the ancient DNA field has transformed our understanding of human genetic history and will keep uncovering the further mysteries of our recent evolutionary past.
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- 2021
134. The adaptive immune system is a major driver of selection for tumor suppressor gene inactivation
- Author
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Stephen J. Elledge, Rupesh S. Patel, Anthony C. Liang, Mamie Z. Li, Danielle R. Cook, Kevin M. Haigis, Timothy D. Martin, Ajinkya Patil, and Mei Yuk Choi
- Subjects
Tumor microenvironment ,Multidisciplinary ,Immune system ,Antigen processing ,Cancer research ,medicine ,Gene silencing ,Biology ,Acquired immune system ,Carcinogenesis ,medicine.disease_cause ,Gene ,Immune checkpoint - Abstract
Defining tumor cell immune evasion Mouse models used to study cancer often lack a full immune system, allowing implantation of human tumors into the mice. By contrast, naturally evolving tumors must contend with a fully functional immune system and its destruction of some of the cells (see the Perspective by Ho and Wood). Two groups now report studies on mouse models with a fully intact immune system. Martin et al . started with preexisting murine tumor cell lines and examined their continued evolution in vivo, whereas Del Poggetto et al . examined the development of new pancreatic tumors in the context of inflammation, as is often seen in human patients. In each study, the authors found that the immune system exerted a selective pressure on cells that would give rise to tumors, promoting the survival of those that had lost expression of tumor suppressor genes or activated a specific oncogene. The findings suggest a major role for the immune system in driving tumor evolution across multiple types of cancer. —YN
- Published
- 2021
135. Silver nanoparticles boost charge-extraction efficiency in Shewanella microbial fuel cells
- Author
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Kenneth H. Nealson, Xun Guan, Gerard C. L. Wong, Zipeng Zhao, Jin Huang, Calvin K. Lee, Bocheng Cao, Xiaoyang Fu, Xiangfeng Duan, Dan Zhu, Chong Liu, Mengning Ding, Lele Peng, Frank Song, Yu Huang, Paul S. Weiss, and Hui-Ying Shiu
- Subjects
chemistry.chemical_classification ,Multidisciplinary ,Microbial fuel cell ,biology ,biology.organism_classification ,Shewanella ,Silver nanoparticle ,Chemical energy ,Electricity generation ,chemistry ,Chemical engineering ,Organic matter ,Sewage treatment ,Bioelectric Energy Sources - Abstract
Silver in the linings The bacterium Shewanella oneidensis is well known to use extracellular electron sinks, metal oxides and ions in nature or electrodes when cultured in a fuel cell, to power the catabolism of organic material. However, the power density of microbial fuel cells has been limited by various factors that are mostly related to connecting the microbes to the anode. Cao et al . found that a reduced graphene oxide–silver nanoparticle anode circumvents some of these issues, providing a substantial increase in current and power density (see the Perspective by Gaffney and Minteer). Electron microscopy revealed silver nanoparticles embedded or attached to the outer cell membrane, possibly facilitating electron transfer from internal electron carriers to the anode. —MAF
- Published
- 2021
136. MIC-Drop: A platform for large-scale in vivo CRISPR screens
- Author
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Calum A. MacRae, Korak Chakraborti, H. Joseph Yost, Zachary P. Harmer, Manu Beerens, Jing-Ruey J. Yeh, Chelsea Herdman, Randall T. Peterson, and Saba Parvez
- Subjects
Multidisciplinary ,biology ,ved/biology ,ved/biology.organism_classification_rank.species ,Mutant ,Cell Culture Techniques ,High-Throughput Nucleotide Sequencing ,Computational biology ,Microfluidic Analytical Techniques ,biology.organism_classification ,Cardiovascular System ,Article ,Animals ,CRISPR ,Genetic Testing ,CRISPR-Cas Systems ,Model organism ,Gene ,Zebrafish ,Function (biology) ,Ribonucleoprotein ,Genetic screen - Abstract
Screen time for CRISPR CRISPR-Cas9 has been used to edit the genomes of organisms ranging from fruit flies to primates, but it has not been used in large-scale genetic screens in animals because generating, validating, and keeping track of large numbers of mutant animals is prohibitively laborious. Parvez et al . have developed Multiplexed Intermixed CRISPR Droplets, or MIC-Drop, a platform combining droplet microfluidics, en masse CRISPR injections, and barcoding, to enable large-scale genetic screens. In pilot phenotypic screens in zebrafish, MIC-Drop enabled rapid identification of the target of a small molecule and discovery of several new genes governing cardiovascular development. MIC-Drop is potentially scalable to thousands of targets and adaptable to diverse organisms and experiments. —DJ
- Published
- 2021
137. Chimeric spike mRNA vaccines protect against Sarbecovirus challenge in mice
- Author
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Elena N. Atochina-Vasserman, Ande West, Sarah R. Leist, Lisa C. Lindesmith, Alexandra Schäfer, Dapeng Li, Robert Parks, Norbert Pardi, Boyd Yount, Maggie Barr, Kevin O. Saunders, Stephanie A. Montgomery, Drew Weissman, Ralph S. Baric, Gabriela De la Cruz, Barton F. Haynes, and David R. Martinez
- Subjects
Sarbecovirus ,0301 basic medicine ,Cross Protection ,viruses ,Antibodies, Viral ,Severe Acute Respiratory Syndrome ,Virus Replication ,Neutralization ,Mice ,Immunogenicity, Vaccine ,0302 clinical medicine ,030212 general & internal medicine ,Mink ,skin and connective tissue diseases ,Lung ,Mice, Inbred BALB C ,Vaccines, Synthetic ,Multidisciplinary ,biology ,Immunogenicity ,virus diseases ,Vaccination ,Titer ,Severe acute respiratory syndrome-related coronavirus ,Spike Glycoprotein, Coronavirus ,Cytokines ,Female ,Spike (software development) ,Antibody ,Coronavirus Infections ,COVID-19 Vaccines ,Recombinant Fusion Proteins ,Heterologous ,Immunity, Heterologous ,Article ,Betacoronavirus ,03 medical and health sciences ,Protein Domains ,Immunity ,biology.animal ,Animals ,Messenger RNA ,SARS-CoV-2 ,fungi ,COVID-19 ,Viral Vaccines ,Breakthrough infection ,biology.organism_classification ,Antibodies, Neutralizing ,Virology ,respiratory tract diseases ,body regions ,universal coronavirus vaccine ,mRNA vaccine ,030104 developmental biology ,Viral replication ,Liposomes ,biology.protein ,Nanoparticles ,SARS-like virus - Abstract
The emergence of SARS-CoV and SARS-CoV-2 in the 21st century highlights the need to develop universal vaccination strategies against the SARS-related Sarbecovirus subgenus. Using structure-guided chimeric spike designs and multiplexed immunizations, we demonstrate protection against SARS-CoV, SARS-CoV-2, and bat CoV (BtCoV) RsSHC014 challenge in highly vulnerable aged mice. Chimeric spike mRNAs containing N-terminal domain (NTD), and receptor binding domains (RBD) induced high levels of broadly protective neutralizing antibodies against three high-risk sarbecoviruses: SARS-CoV, RsSHC014, and WIV-1. In contrast, SARS-CoV-2 mRNA vaccination not only showed a 10 to >500-fold reduction in neutralizing titers against heterologous sarbecovirus strains, but SARS-CoV challenge in mice resulted in breakthrough infection including measurable lung pathology. Importantly, chimeric spike mRNA vaccines efficiently neutralized both the D614G and the South African B.1.351 variants of concern despite some reduction in neutralization activity. Thus, multiplexed-chimeric spikes may provide a novel strategy to prevent pandemic and SARS-like zoonotic coronavirus infections, while revealing the limited efficacy of SARS-CoV-2 spike vaccines against other sarbecoviruses.
- Published
- 2021
138. Identification of a quality-control factor that monitors failures during proteasome assembly
- Author
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Eszter Zavodszky, Sew-Yeu Peak-Chew, Ana J. Narvaez, Ramanujan S. Hegde, and Szymon Juszkiewicz
- Subjects
Proteasome Endopeptidase Complex ,Ubiquitin-Protein Ligases ,Protein subunit ,Mutation, Missense ,PSMC5 ,Article ,Mice ,Calmodulin ,Ubiquitin ,Proto-Oncogene Proteins ,Animals ,Humans ,Point Mutation ,Protein Interaction Domains and Motifs ,Adaptor Proteins, Signal Transducing ,Multidisciplinary ,biology ,Chemistry ,Ubiquitination ,Signal transducing adaptor protein ,Neurodegenerative Diseases ,Ubiquitin ligase ,Cell biology ,Protein Subunits ,Proteasome ,Chaperone (protein) ,Proteasome assembly ,Mutation ,Proteolysis ,MCF-7 Cells ,biology.protein ,ATPases Associated with Diverse Cellular Activities - Abstract
Safeguarding protein complex assembly The assembly of multiprotein complexes inside the cell requires each subunit to be produced at a defined level relative to its partners. Imbalances in subunit synthesis are inevitable, necessitating the elimination of unassembled intermediates. Zavodszky et al . found that a ubiquitin ligase called HERC1 is responsible for marking certain assembly intermediates of the proteasome for degradation. HERC1 finds these intermediates by recognizing a proteasome assembly factor that normally dissociates when assembly is complete. A point mutation in HERC1 that impairs its ability to recognize proteasome assembly intermediates causes neurodegeneration in mice, highlighting the importance of this quality control pathway. —SMH
- Published
- 2021
139. RNA editing restricts hyperactive ciliary kinases
- Author
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Dongdong Li, Jin Billy Li, Qiangfeng Cliff Zhang, Peishan Yi, Zhiwen Zhu, Guangshuo Ou, Yufan Liu, and Wei Li
- Subjects
Transcription, Genetic ,Adenosine Deaminase ,RNA Splicing ,RNA Stability ,Protein Serine-Threonine Kinases ,Biology ,Transcription (biology) ,RNA Precursors ,Protein biosynthesis ,Animals ,RNA, Antisense ,Cilia ,RNA, Messenger ,Caenorhabditis elegans ,Caenorhabditis elegans Proteins ,Protein kinase A ,RNA, Double-Stranded ,Cell Nucleus ,Messenger RNA ,Multidisciplinary ,Intron ,RNA ,Cell biology ,Enzyme Activation ,Phenotype ,RNA editing ,Protein Biosynthesis ,RNA splicing ,RNA Editing ,Mitogen-Activated Protein Kinases ,RNA, Helminth ,Signal Transduction - Abstract
Protein kinase activity must be precisely regulated, but how a cell governs hyperactive kinases remains unclear. In this study, we generated a constitutively active mitogen-activated protein kinase DYF-5 (DYF-5CA) in Caenorhabditis elegans that disrupted sensory cilia. Genetic suppressor screens identified that mutations of ADR-2, an RNA adenosine deaminase, rescued ciliary phenotypes of dyf-5CA We found that dyf-5CA animals abnormally transcribed antisense RNAs that pair with dyf-5CA messenger RNA (mRNA) to form double-stranded RNA, recruiting ADR-2 to edit the region ectopically. RNA editing impaired dyf-5CA mRNA splicing, and the resultant intron retentions blocked DYF-5CA protein translation and activated nonsense-mediated dyf-5CA mRNA decay. The kinase RNA editing requires kinase hyperactivity. The similar RNA editing-dependent feedback regulation restricted the other ciliary kinases NEKL-4/NEK10 and DYF-18/CCRK, which suggests a widespread mechanism that underlies kinase regulation.
- Published
- 2021
140. Rare variant MX1 alleles increase human susceptibility to zoonotic H7N9 influenza virus
- Author
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Georg Kochs, Yuelong Shu, Jian Lu, Qijun Liao, Y. Chen, Tian Bai, Lei Yang, Wenfei Zhu, Otto Haller, Philipp P. Petric, Peter Staeheli, Juan Shen, Tao Chen, Martin Schwemmle, Laura Graf, Jie Dong, Dayan Wang, and Ying Chen
- Subjects
Avian Influenza A Virus ,Multidisciplinary ,Genetic variation ,Influenza A virus ,medicine ,Heterozygote advantage ,Transfection ,Allele ,Biology ,medicine.disease_cause ,Gene ,Virology ,Virus - Abstract
Poultry passport to pandemic What conditions are required to nurture the seeds of a pandemic? The avian influenza virus H7N9 rarely spills over into humans, but when it does, mortality exceeds 30%, far in excess of that of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Chen et al . used whole-genome sequencing to investigate the contribution of rare mutations among poultry workers who can be exposed to high levels of H7N9. Multiple defective single-nucleotide variants in the myxovirus resistance Mx1 locus were prevalent in H7N9 patients. In vitro infection experiments and influenza polymerase activity assays showed that 14 of the 17 MxA protein variants had no antiviral activity. Thus, individuals with such genetic vulnerabilities, when exposed to high virus loads, may act as crucibles for transmission of virulent new influenza subtypes. —CA
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- 2021
141. Malaria infection and severe disease risks in Africa
- Author
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Alice Kamau, George Mtove, Hugh Reyburn, Sunetra Gupta, Arthur Mpimbaza, Charles Mwandawiro, Bryan O. Nyawanda, Robert S. Paton, Amina F. Mohamed, Nancy A. Otieno, Robert W. Snow, Samuel Akech, Simon Kariuki, Philip Bejon, Neema Mturi, Ambrose Agweyu, Shebe Mohammed, José Lourenço, and Morris Ogero
- Subjects
Plasmodium falciparum ,Malaria, Cerebral ,Severe disease ,macromolecular substances ,Disease ,Severity of Illness Index ,Risk Factors ,Environmental health ,parasitic diseases ,Severity of illness ,Prevalence ,East africa ,Humans ,Medicine ,Severe Malaria ,Malaria, Falciparum ,Child ,Models, Statistical ,Multidisciplinary ,biology ,business.industry ,Incidence ,Incidence (epidemiology) ,Age Factors ,Infant ,Bayes Theorem ,Africa, Eastern ,medicine.disease ,biology.organism_classification ,Hospitalization ,Child, Preschool ,Epidemiological Monitoring ,business ,Malaria - Abstract
The relationship between community prevalence of Plasmodium falciparum and the burden of severe, life-threatening disease remains poorly defined. To examine the three most common severe malaria phenotypes from catchment populations across East Africa, we assembled a dataset of 6506 hospital admissions for malaria in children aged 3 months to 9 years from 2006 to 2020. Admissions were paired with data from community parasite infection surveys. A Bayesian procedure was used to calibrate uncertainties in exposure (parasite prevalence) and outcomes (severe malaria phenotypes). Each 25% increase in prevalence conferred a doubling of severe malaria admission rates. Severe malaria remains a burden predominantly among young children (3 to 59 months) across a wide range of community prevalence typical of East Africa. This study offers a quantitative framework for linking malaria parasite prevalence and severe disease outcomes in children.
- Published
- 2021
142. A fossil record of land plant origins from charophyte algae
- Author
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Paul K. Strother and Clinton B. Foster
- Subjects
Spores ,Geologic Sediments ,Multidisciplinary ,Fossil Record ,biology ,Phylogenetic tree ,Fossils ,Ecology ,Charophyceae ,fungi ,Embryophyte ,Western Australia ,social sciences ,biology.organism_classification ,Time gap ,Biological Evolution ,Tremadocian ,Geography ,Algae ,Ordovician ,Embryophyta ,Assemblage (archaeology) ,Genome, Plant ,Phylogeny - Abstract
Molecular time trees indicating that embryophytes originated around 500 million years ago (Ma) during the Cambrian are at odds with the record of fossil plants, which first appear in the mid-Silurian almost 80 million years later. This time gap has been attributed to a missing fossil plant record, but that attribution belies the case for fossil spores. Here, we describe a Tremadocian (Early Ordovician, about 480 Ma) assemblage with elements of both Cambrian and younger embryophyte spores that provides a new level of evolutionary continuity between embryophytes and their algal ancestors. This finding suggests that the molecular phylogenetic signal retains a latent evolutionary history of the acquisition of the embryophytic developmental genome, a history that perhaps began during Ediacaran-Cambrian time but was not completed until the mid-Silurian (about 430 Ma).
- Published
- 2021
143. Secreted pectin monooxygenases drive plant infection by pathogenic oomycetes
- Author
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Michael Csukai, Paul H. Walton, Lydia Welsh, Anna O. Avrova, Peter J. Lindley, Neil C. Bruce, Bernard Henrissat, Julie Squires, Gideon J. Davies, Stephen C. Whisson, Simon J. McQueen-Mason, Federico Sabbadin, Saioa Urresti, Architecture et fonction des macromolécules biologiques (AFMB), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of York [York, UK], Instituto Biofisika, and Universidad del Pais Vasco / Euskal Herriko Unibertsitatea [Espagne] (UPV/EHU)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)
- Subjects
Models, Molecular ,MESH: Oxidation-Reduction ,0106 biological sciences ,Protein Conformation ,[SDV]Life Sciences [q-bio] ,01 natural sciences ,Mixed Function Oxygenases ,MESH: Protein Conformation ,MESH: Plant Diseases ,Solanum lycopersicum ,MESH: Lycopersicon esculentum ,Pathogen ,2. Zero hunger ,Oomycete ,0303 health sciences ,Multidisciplinary ,biology ,food and beverages ,MESH: Mixed Function Oxygenases ,MESH: Copper ,MESH: Plant Leaves ,Lytic cycle ,Phytophthora infestans ,Pectins ,MESH: Protein Domains ,Oxidation-Reduction ,MESH: Models, Molecular ,Virulence Factors ,Virulence ,MESH: Solanum tuberosum ,Microbiology ,Cell wall ,03 medical and health sciences ,Protein Domains ,Polysaccharides ,Gene ,Plant Diseases ,Solanum tuberosum ,MESH: Virulence Factors ,030304 developmental biology ,Host (biology) ,fungi ,biology.organism_classification ,Plant Leaves ,MESH: Polysaccharides ,MESH: Phytophthora infestans ,Copper ,MESH: Pectins ,010606 plant biology & botany - Abstract
Potato pectin falls to Phytophthora Phytophthora infestans is a plant oomycete pathogen that drove the potato famines of the 1800s and continues to afflict potato fields today. The polysaccharide pectin makes up about a third of the cell wall in potatoes. Sabbadin et al . identified a family of lytic polysaccharide monooxygenases (LMPOs) that cleave pectin and are upregulated in P. infestans during infection. Silencing the relevant LMPO gene successfully inhibited P. infestans infections. These findings open doors for disease intervention targets and for biotech applications. —PJH
- Published
- 2021
144. Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants
- Author
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Nicholas C. Wu, Xueyong Zhu, Marit J. van Gils, Jakob Kreye, Chang-Chun D Lee, Linghang Peng, Hejun Liu, Meng Yuan, Abigail M. Jackson, Dennis R. Burton, Andrew B. Ward, Rogier W. Sanders, David Nemazee, S. Momsen Reincke, Harald Prüss, Ian A. Wilson, Deli Huang, Medical Microbiology and Infection Prevention, and AII - Infectious diseases
- Subjects
virology [COVID-19] ,medicine.disease_cause ,Antibodies, Viral ,metabolism [Angiotensin-Converting Enzyme 2] ,genetics [Spike Glycoprotein, Coronavirus] ,Neutralization ,Germline ,Epitopes ,genetics [Antigens, Viral] ,immunology [SARS-CoV-2] ,immunology [COVID-19] ,Antigens, Viral ,Coronavirus ,chemistry.chemical_classification ,Mutation ,Multidisciplinary ,Microbio ,genetics [SARS-CoV-2] ,spike protein, SARS-CoV-2 ,Antigenic Variation ,Vaccination ,Spike Glycoprotein, Coronavirus ,chemistry [Antigens, Viral] ,ddc:500 ,Angiotensin-Converting Enzyme 2 ,Antibody ,chemistry [SARS-CoV-2] ,Protein Binding ,chemistry [Spike Glycoprotein, Coronavirus] ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,ACE2 protein, human ,metabolism [Antibodies, Neutralizing] ,Biology ,Receptor binding site ,Article ,Antigenic drift ,immunology [Antibodies, Viral] ,Protein Domains ,Report ,medicine ,Humans ,metabolism [Receptors, Coronavirus] ,Gene ,Immune Evasion ,Binding Sites ,metabolism [Antibodies, Viral] ,immunology [Spike Glycoprotein, Coronavirus] ,SARS-CoV-2 ,Biochem ,COVID-19 ,Virology ,immunology [Antigens, Viral] ,Antibodies, Neutralizing ,immunology [Antibodies, Neutralizing] ,metabolism [Antigens, Viral] ,Enzyme ,chemistry ,metabolism [Spike Glycoprotein, Coronavirus] ,biology.protein ,Binding Sites, Antibody ,Reports ,Receptors, Coronavirus - Abstract
The protective efficacy of neutralizing antibodies (nAbs) elicited during natural infection with SARS-CoV-2 and by vaccination based on its spike protein has been compromised with emergence of the recent SARS-CoV-2 variants. Residues E484 and K417 in the receptor-binding site (RBS) are both mutated in lineages first described in South Africa (B.1.351) and Brazil (B.1.1.28.1). The nAbs isolated from SARS-CoV-2 patients are preferentially encoded by certain heavy-chain germline genes and the two most frequently elicited antibody families (IGHV3-53/3-66 and IGHV1-2) can each bind the RBS in two different binding modes. However, their binding and neutralization are abrogated by either the E484K or K417N mutation, whereas nAbs to the cross-reactive CR3022 and S309 sites are largely unaffected. This structural and functional analysis illustrates why mutations at E484 and K417 adversely affect major classes of nAbs to SARS-CoV-2 with consequences for next-generation COVID-19 vaccines.
- Published
- 2021
145. SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern
- Author
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M. Alejandra Tortorici, Alessandra Franzetti Pellanda, Amalio Telenti, Alexandra C. Walls, Christian Garzoni, Jessica Bassi, Herbert W. Virgin, Mary-Jane Navarro, David Veesler, Christian Saliba, Alexander Chen, Matthew McCallum, Katja Culap, Sonja Bernasconi Guastalla, Chiara Silacci-Fregni, Gyorgy Snell, Elisabetta Cameroni, Luca Piccoli, Wesley C. Van Voorhis, Matteo Samuele Pizzuto, Laura E. Rosen, John E. Bowen, Siro Bianchi, Anna De Marco, Stefano Jaconi, Dora Pinto, Maria De Agostini, Giovanni Bona, Kaitlin R. Sprouse, Julia di Iulio, Sasha W Tilles, and Davide Corti
- Subjects
chemistry.chemical_classification ,Signal peptide ,Mutation ,Messenger RNA ,Multidisciplinary ,medicine.drug_class ,Protein domain ,Biology ,medicine.disease_cause ,Monoclonal antibody ,Virology ,Neutralization ,chemistry ,Antigen ,medicine ,Glycoprotein - Abstract
SARS-CoV-2 from alpha to epsilon As battles to contain the COVID-19 pandemic continue, attention is focused on emerging variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that have been deemed variants of concern because they are resistant to antibodies elicited by infection or vaccination or they increase transmissibility or disease severity. Three papers used functional and structural studies to explore how mutations in the viral spike protein affect its ability to infect host cells and to evade host immunity. Gobeil et al . looked at a variant spike protein involved in transmission between minks and humans, as well as the B1.1.7 (alpha), B.1.351 (beta), and P1 (gamma) spike variants; Cai et al . focused on the alpha and beta variants; and McCallum et al . discuss the properties of the spike protein from the B1.1.427/B.1.429 (epsilon) variant. Together, these papers show a balance among mutations that enhance stability, those that increase binding to the human receptor ACE2, and those that confer resistance to neutralizing antibodies. —VV
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- 2021
146. A noncoding RNA modulator potentiates phenylalanine metabolism in mice
- Author
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Yaohua Zhang, V. Reid Sutton, Youqiong Ye, Chunru Lin, Lan Liao, Zhao Zhang, Yajuan Li, Shuxing Zhang, Nenad Blau, Cristian Coarfa, Manuel Schiff, Ke Liang, Sergey D. Egranov, Zhi Tan, Preethi H. Gunaratne, Qingsong Hu, Kuang-Lei Tsai, Yi Chuan Li, Yao Jun, Jean-Louis Guéant, François Feillet, Mien Chie Hung, Chunlai Li, Nagireddy Putluri, Tina K. Nguyen, David H. Hawke, Heidi Hsiao, George A. Calin, Ania C. Muntau, Zhen Xing, Sujash S. Chatterjee, Liuqing Yang, Farès Namour, Leng Han, Yinghong Pan, and Jianming Xu
- Subjects
Male ,Functional role ,Acetylgalactosamine ,RNA, Untranslated ,HULC ,Phenylalanine hydroxylase ,Phenylalanine ,Computational biology ,Plasma protein binding ,Article ,Mice ,Metabolic Diseases ,Phenylketonurias ,Drug Discovery ,medicine ,Animals ,Humans ,Pharmacology ,Mice, Knockout ,Multidisciplinary ,biology ,Chemistry ,Metabolic disorder ,Phenylalanine Hydroxylase ,RNA ,General Medicine ,medicine.disease ,Non-coding RNA ,Biopterin ,Diet ,Disease Models, Animal ,MicroRNAs ,Liver ,Biochemistry ,Hepatocytes ,biology.protein ,Nucleic Acid Conformation ,Female ,RNA, Long Noncoding ,Phenylalanine metabolism ,Protein Binding - Abstract
The functional role of long noncoding RNAs (lncRNAs) in inherited metabolic disorders, including phenylketonuria (PKU), is unknown. We demonstrated that the mouse lncRNA Pair and human HULC associate with phenylalanine hydroxylase (PAH). Pair-knockout mice exhibited excessive blood phenylalanine, musty odor, hypopigmentation, growth retardation, and progressive neurological symptoms including seizures, which faithfully models human PKU. HULC depletion led to reduced PAH enzymatic activities in human induced pluripotent stem cell (hiPSC)-differentiated hepatocytes. Mechanistically, HULC modulated the enzymatic activities of PAH by facilitating PAH-substrate and PAH-cofactor interactions. To develop a therapeutic strategy for restoring liver lncRNAs, we designed GalNAc-tagged lncRNA mimics that exhibit liver enrichment. Treatment with GalNAc-HULC mimics reduced excessive phenylalanine in Pair(−/−) and Pah(R408W/R408W) mice and improved the phenylalanine tolerance of these mice.
- Published
- 2021
147. Acrobatic squirrels learn to leap and land on tree branches without falling
- Author
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Lucia F. Jacobs, Robert J. Full, Judy Jinn, and Nathaniel H. Hunt
- Subjects
0303 health sciences ,Arboreal locomotion ,Multidisciplinary ,biology ,Computer science ,Extramural ,biology.organism_classification ,03 medical and health sciences ,Tree (data structure) ,0302 clinical medicine ,Aeronautics ,Falling (sensation) ,ComputingMilieux_MISCELLANEOUS ,030217 neurology & neurosurgery ,LEAPS ,030304 developmental biology ,Sciurus - Abstract
Arboreal animals often leap through complex canopies to travel and avoid predators. Their success at making split-second, potentially life-threatening decisions of biomechanical capability depends on their skillful use of acrobatic maneuvers and learning from past efforts. Here, we found that free-ranging fox squirrels (Sciurus niger) leaping across unfamiliar, simulated branches decided where to launch by balancing a trade-off between gap distance and branch-bending compliance. Squirrels quickly learned to modify impulse generation upon repeated leaps from unfamiliar, compliant beams. A repertoire of agile landing maneuvers enabled targeted leaping without falling. Unanticipated adaptive landing and leaping "parkour" behavior revealed an innovative solution for particularly challenging leaps. Squirrels deciding and learning how to launch and land demonstrates the synergistic roles of biomechanics and cognition in robust gap-crossing strategies.
- Published
- 2021
148. Horizontally transmitted parasitoid killing factor shapes insect defense to parasitoids
- Author
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Yonggyun Kim, Madoka Nakai, Shiori Sagawa, Jun Takatsuka, David A. Theilmann, Rie Ohta, Cathy Coutu, Aki Kida, Stephanie Harris, Laila Gasmi, Ken Tateishi, Kazuyo Watanabe, Salvador Herrero, Martin A. Erlandson, Mohammad Vatanparast, Maki N. Inoue, Doug Baldwin, Shohei Okuno, Mio Kawabata, Dwayne D. Hegedus, Edyta A. L. Sieminska, and Yasuhisa Kunimi
- Subjects
Gene Transfer, Horizontal ,media_common.quotation_subject ,Genome, Insect ,Wasps ,Zoology ,Parasitism ,Apoptosis ,Insect Viruses ,Insect ,Spodoptera ,Competition (biology) ,Host-Parasite Interactions ,Parasitoid ,Lepidoptera genitalia ,Viral Proteins ,03 medical and health sciences ,0302 clinical medicine ,Evolutionary arms race ,Animals ,030304 developmental biology ,media_common ,0303 health sciences ,Multidisciplinary ,biology ,Host (biology) ,fungi ,biology.organism_classification ,Biological Evolution ,Microgastrinae ,Nucleopolyhedroviruses ,Lepidoptera ,Larva ,Entomopoxvirinae ,Insect Proteins ,030217 neurology & neurosurgery - Abstract
Protection from parasitism by a virus Parasitoid wasps have developed myriad systems to overcome the defense mechanisms of their hosts as they lay their eggs in the bodies and eggs of targeted species. Gasmi et al . report how the host can fight back when infected by a virus that expresses a protein conferring resistance to the parasitoid. When members of the butterfly and moth family are targeted by wasps, a protein family has evolved that is horizontally carried by viruses—and sometimes is incorporated into the host genome—and impairs the ability of parasitoid offspring to fully develop and emerge. Characterizing the ability of this protein to protect hosts against specific parasites, the authors document an ongoing host-parasite evolutionary arms race. —LMZ
- Published
- 2021
149. Plant 'helper' immune receptors are Ca 2+ -permeable nonselective cation channels
- Author
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Pierre Jacob, Li Wan, Korina Kempthorn, William G. Walton, Zhen-Ming Pei, Matthew R. Redinbo, Adam D. Lietzan, Nak Hyun Kim, Farid El-Kasmi, Jeffery L. Dangl, Fei-Hua Wu, Oliver J. Furzer, Yuan Chi, and Sruthi Sunil
- Subjects
Programmed cell death ,Multidisciplinary ,Immune system ,biology ,Chemistry ,Cytoplasm ,Arabidopsis ,HEK 293 cells ,Patch clamp ,biology.organism_classification ,Receptor ,Calcium signaling ,Cell biology - Abstract
Calcium signaling for host cell death In response to microbial pathogens, some plants kill off their own cells to limit further spread of infection. The Toll/Interleukin-1 receptor/Resistance class of nucleotide-binding leucine-rich repeat receptors (known as TNLs) function in plants as immune receptors. These TNLs work together with a dedicated set of helper proteins. Jacob et al. reveal the structure of one of these helpers known as NRG1 (N REQUIREMENT GENE 1). The structure resembles a known animal cation channel. The authors demonstrate that helper NLRs directly control calcium ion influx to initiate host cell death, providing a mechanism for TNL outputs. Science , abg7917, this issue p. 420
- Published
- 2021
150. Neural representations of space in the hippocampus of a food-caching bird
- Author
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Dmitriy Aronov, Galen F. Lynch, and Hannah L Payne
- Subjects
Male ,0301 basic medicine ,Action Potentials ,Hippocampus ,Sensory system ,Cognitive neuroscience ,Hippocampal formation ,Article ,03 medical and health sciences ,0302 clinical medicine ,biology.animal ,Behavioral ecology ,Neural Pathways ,Animals ,Passeriformes ,Spatial Memory ,Neurons ,Multidisciplinary ,biology ,Vertebrate ,Feeding Behavior ,Sleep in non-human animals ,Electrophysiological Phenomena ,030104 developmental biology ,Place Cells ,Spatial ecology ,Female ,Finches ,Sleep ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Conserved spatial memory mechanisms Food-caching birds are memory specialists that can remember thousands of hidden food items. Using electrophysiological recordings from freely behaving birds, Payne et al. analyzed neuronal activity in the likely hippocampus homolog of two bird species, the tufted titmouse and the zebra finch. They chose these two species to compare, respectively, birds that do and do not display food-caching behavior. Place cells and typical hippocampal firing patterns that resembled rodent neuronal activity could be detected in the extreme memory specialists. Compared with titmice, however, spatial activity was noticeably weaker and less abundant in zebra finches. These findings provide evidence that the neural processes underlying spatial memory are remarkably conserved across widely divergent hippocampal circuits separated by millions of years of evolution. Science , abg2009, this issue p. 343
- Published
- 2021
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