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Cell - Life Science Journal Logo
11.04.21 22:00 Kinase-mediated RAS signaling via membraneless cytoplasmic protein granules

Schlagwörter: Live-cell, EML4-ALK, Beas2B

Receptor tyrosine kinase fusion oncoproteins undergo higher-order assembly to form membraneless cytoplasmic protein granules that coordinate local RAS activation and organize RAS/MAPK signaling in cancer

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11.04.21 22:00 Programmable protein circuit design

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A growing toolbox of programmable protein circuit components offers flexibility and rapid responsiveness compared with nucleic-acid-based synthetic circuits.

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08.04.21 22:00 Genome-wide programmable transcriptional memory by CRISPR-based epigenome editing

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CRISPRoff programs heritable epigenetic memory and is able to heritably silence most genes, including genes without CpG islands. This heritable silencing is highly specific and persists through differentiation of iPSCs into neurons.

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08.04.21 22:00 The long-term genetic stability and individual specificity of the human gut microbiome

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A longitudinal analysis of 338 individuals across 4 years characterizes the temporal stability and diversity of human gut microbiome, linking the microbial profile with individual-specific host phenotypes and suggesting the role of plasma metabolites in mediating the impact of microbiome on host physiology.

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06.04.21 22:00 Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes

Dentro et al. provide a comprehensive annotation of intra-tumor heterogeneity and its drivers in cancer evolution.

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05.04.21 22:00 The origins of viral infection sleuth

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The events of the past year have underscored the serious and rapid threat that emerging viruses pose to global health. However, much of the rapid progress in understanding and combating SARS-CoV-2 was made possible because of the decades of important groundwork laid from researchers studying other emergent infectious diseases. The 2021 John Dirks Canada Gairdner Global Health award recognizes the contributions of Joseph Sriyal Malik Peiris and Yi Guan toward understanding the origins and options

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05.04.21 22:00 One world, one health

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The past year has underscored the threat that emerging viruses pose to global health. The 2021 John Dirks Canada Gairdner Global Health award recognizes the contributions of Joseph Sriyal Malik Peiris and Yi Guan toward understanding the origins and options for control of newly emerging infectious disease outbreaks in Asia, notably zoonotic influenza and severe acute respiratory syndrome (SARS). Nicole Neuman of Cell corresponded with Malik Peiris about his path to studying emerging infectious d

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05.04.21 22:00 The islet’s bridesmaid becomes the bride: Proglucagon-derived peptides deliver transformative therapies

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The 2021 Gairdner Prize is awarded to Daniel Drucker, Joel Habener, and Jens Juul Holst for the discovery of novel peptides encoded in the proglucagon sequence and the establishment of their physiological roles. These discoveries underpinned the development of therapeutics that are now benefiting patients with type 2 diabetes and other disorders worldwide.

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05.04.21 22:00 Transforming lives through genetics

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Mary-Claire King’s approach to genetics has had a major impact on breast and ovarian cancer and, more recently, mental illnesses including schizophrenia. Science writer Kendall Morgan talked with Mary-Claire, recipient of a 2021 Canada Gairdner International Award, about her life, her lengthy quest to discover the genetic basis of susceptibility to breast cancer, the struggles for women in science, and much more. An edited version of this conversation is presented below.

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05.04.21 22:00 Connecting communities to tackle cancer from many sides

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Interdisciplinary work has played a key role in Dr. Elizabeth Eisenhauer’s wide-ranging research contributions and leadership in cancer clinical trials, drug delivery, treatment standards, and research and prevention strategy. Cell editor Emma Yee talked with Dr. Eisenhauer, recipient of the 2021 Canada Gairdner Wightman Award, to learn more about the factors that influenced her work in cancer care and the lessons she learned along the way. This conversation is presented below, edited for clarit

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05.04.21 22:00 Bioelectric signaling: Reprogrammable circuits underlying embryogenesis, regeneration, and cancer

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Michael Levin provides a perspective on how bioelectric circuits—beyond neurons—integrate information across cell, tissue, organ, and whole-body scales to enable morphogenesis and pattern homeostasis. A roadmap for exploiting bioelectric communication to treat developmental disorders, promote regeneration, reprogram cancer, and engineer living things is presented.

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01.04.21 22:00 The aging lung: Physiology, disease, and immunity

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Recent cellular and molecular studies have given insight into why the incidence and/or severity of many lung diseases, from lung cancer to COVID-19, increase with age.

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01.04.21 22:00 Early introductions and transmission of SARS-CoV-2 variant B.1.1.7 in the United States

Schlagwörter: Grubaugh, Further, Contact, Nathan, Lead

The SARS-CoV-2 variant B.1.1.7 was introduced to the United States in early December 2020 and soon became established within many communities. The primary points of entry into the US are identified as NY, CA, and FL, and exponential growth in these states resulted in spread to neighboring states.

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30.03.21 22:00 Elevated rates of horizontal gene transfer in the industrialized human microbiome

Schlagwörter: Bacteroides, This, HGTs, BMI, B

A worldwide microbiome analysis from 15 populations along the industrialization gradient reveals that horizontal gene transfer occurs on short timescales and that microbiomes continuously acquire new functionality based on host lifestyle.

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29.03.21 22:00 Antibody evasion by the P.1 strain of SARS-CoV-2

Schlagwörter: Reset, You, If

Structural and functional analysis of the P.1 variant of SARS-CoV-2 from Brazil reveals less resistance to antibodies generated from natural infection or vaccination compared to another similar variant, B.1.351. A monoclonal antibody mAb 222 is able to neutralize all three variants (P.1, B.1.351 and B.1.1.7), with its light chain able to restore neutralization potency to broad group of antibodies.

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29.03.21 22:00 Emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States

Schlagwörter: Reset, You, If

Genomic epidemiology analyses explain the introduction and transmission of the B.1.1.7 variant of SARS-CoV-2 into the United States, with projections for it to soon be the dominant strain in the country.

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29.03.21 22:00 TOP1 inhibition therapy protects against SARS-CoV-2-induced lethal inflammation.

Schlagwörter: Reset, You, If

Inhibition of topoisomerase 1 through the FDA-approved molecule Topotecan suppresses SARS-CoV-2 infection associated lethal inflammation in hamster and mouse models without compromising antiviral immune responses.

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28.03.21 22:00 Genetic requirements for cell division in a genomically minimal cell

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A reverse genetics approach determined that seven genes are required together for normal cell division in a genomically minimal cell; these include two known cell division genes, ftsZ and sepF, a hydrolase of unknown substrate, and four genes that encode membrane-associated proteins of unknown function.

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24.03.21 23:00 Dual modes of CRISPR-associated transposon homing

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CRISPR-associated transposases (CASTs) undergo RNA-guided transposition. However, they are almost never found in sites targeted by the crRNAs encoded by the cognate CRISPR array, but instead in specific loci on host bacteria genome. This study by Saito et al. reveals two different mechanisms whereby CASTs achieve this “homing” insertion.

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24.03.21 23:00 Whitefly hijacks a plant detoxification gene that neutralizes plant toxins

The cosmopolitan agricultural pest Bemisia tabaci has acquired a plant-derived gene through a plant-to-insect horizontal gene transfer event. This acquired gene allows whiteflies to detoxify plant defense compounds and continue to feed on their plant hosts.

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23.03.21 23:00 Nonpeptidergic neurons suppress mast cells via glutamate to maintain skin homeostasis

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A subset of sensory neurons marked by MrgprD maintain skin homeostasis by suppressing mast cell inflammatory responses.

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23.03.21 23:00 An early cell shape transition drives evolutionary expansion of the human forebrain

Schlagwörter: SiMView, Images, Scale, Live, Note

Cerebral organoid models reveal that differences in the duration of a developmental transitional state driven by the factor ZEB2 underlie the basis of brain expansion in humans in comparison to great apes.

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23.03.21 23:00 Genetically engineered myeloid cells rebalance the core immune suppression program in metastasis

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Genetically engineered myeloid cells expressing IL-12 can reverse the immunosuppressive environment developed during metastatic progression by augmenting T cell responses and reducing metastatic burden in preclinical models.

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23.03.21 23:00 The molecular basis for sarcomere organization in vertebrate skeletal muscle

Schlagwörter: Slices, A-band, Myosin, Z-disc

Visualizing the mouse sarcomere in the rigor state using electron cryo-tomography reveals architectural details of the different zones and provides insight into how key factors are arranged within them to support function during muscle contraction.

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23.03.21 23:00 Creating collaboration by breaking down scientific barriers

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The scientific world rewards the individual while often discouraging collaboration. However, times of crisis show us how much more we can accomplish when we work together. Here, we describe our approach to breaking down silos and fostering global collaborations and share the lessons we have learned, especially pertaining to research on SARS-CoV-2.

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22.03.21 23:00 A non-canonical type 2 immune response coordinates tuberculous granuloma formation and epithelialization

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During mycobacterial infections, a non-canonical type 2 immune response underlies the formation and epithelial architecture of the granuloma, the hallmark structure of tuberculosis.

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22.03.21 23:00 Archaeogenomic distinctiveness of the Isthmo-Colombian area

Schlagwörter: Post-mortem, X/Ancient, X/Modern, Atlantic, Anzick-1

Pre-contact and modern genomes from Panama highlight the distinctiveness of the Isthmo-Colombian area; detail number, source, and impact of Indigenous American genomic ancestries at the continental level; and explain complex pre-Hispanic burials.

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19.03.21 23:00 SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies

Comparison of the SARS-CoV-2 variants B.1.1.7, B.1.351 and P.1 show that inhibitors under clinical evaluation are still effective in blocking entry though the B.1.351 and P.1 variants evade antibody responses induced upon infection as well as vaccination and evade certain therapeutic antibodies.

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18.03.21 23:00 Delineating the conformational landscape of the adenosine A2A receptor during G protein coupling

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Monitoring conformational ensembles of a GPCR along the entire activation pathway in lipid bilayer captures key receptor states associated with G protein coupling and uncovers the role of Gβγ in facilitating ligand-dependent allosteric signal transmission.

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17.03.21 23:00 Simultaneous binding of Guidance Cues NET1 and RGM blocks extracellular NEO1 signaling

When extracellular guidance molecules Netrin and RGM that have opposing functions simultaneously bind the Neogenin receptor, a super-complex is formed that diminishes their functional outputs.

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16.03.21 23:00 Structure and gating mechanism of the α7 nicotinic acetylcholine receptor

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Cryo-EM structures of the α7 nicotinic acetylcholine receptor in three major conformational states of the gating cycle—resting, activated, and desensitized—along with functional studies reveal components involved in calcium conductance and allosteric coupling of ligand binding to channel opening.

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16.03.21 23:00 B cell-specific XIST complex enforces X-inactivation and restrains atypical B cells

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XIST restrains human atypical B cell development. A distinct XIST-associated protein complex contributes to XIST-mediated gene silencing in B cells.

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15.03.21 23:00 Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein

Schlagwörter: KeywordsCoronavirus, Neutralizing, Monoclonal, N-terminal, Viral

Suryadevara et al. find neutralizing antibodies to the spike protein N-terminal domain that arise from natural infection with SARS-CoV-2. These antibodies inhibit post-attachment steps of the viral cycle and initiate protective immune responses via the antibody Fc domain.

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15.03.21 23:00 N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2

McCallum et al. identify a supersite in the N-terminal domain of SARS-CoV-2 spike protein that is targeted by neutralizing antibodies and exhibits mutation in response to selective pressure.

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15.03.21 23:00 SARS-CoV-2 evolution in an immunocompromised host reveals shared neutralization escape mechanisms

Structural and functional analysis of the evolution of SARS-CoV-2 in a persistently infected immunocompromised individual yields insights into mutations that foreshadow emerging viral variants worldwide.

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15.03.21 23:00 BET Inhibition Blocks Inflammation-Induced Cardiac Dysfunction and SARS-CoV-2 Infection

A combination of phosphoproteomics, drug screening and single-cell sequencing approaches identifies how cytokines elevated in COVID-19 patients drives cardiac dysfunction, with BET inhibitors serving as potential lead candidates decrease ACE2 cardiac expression and infection.

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15.03.21 23:00 Rigidity percolation uncovers a structural basis for embryonic tissue phase transitions

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A general theoretical approach, rooted in cell connectivity, enables prediction of phase transitions at the tissue scale.

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11.03.21 23:00 Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity

Analyses of sera from individuals vaccinated with one or two doses of mRNA vaccines against 10 circulating variants of SARS-CoV-2 show that P.1 and B.1.351 in particular exhibit limited neutralization by vaccine-induced humoral immunity. This escape was found to be largely mediated by mutations in the receptor-binding domain of SARS-CoV-2 spike.

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10.03.21 23:00 Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions

Schlagwörter: UV-crosslinking, Intersection, DrugCentral, SARS-CoV-2, Includes

Interrogation of SARS-CoV-2 RNA-host protein interaction networks by ChIRP-MS and CRISPR screens, in comparison with other human viruses such as flaviviruses, picornavirus, and rhinovirus, identifies complexes specific to SARS-CoV-2 infection and highlights the role of mitochondria in mediating antiviral immunity.

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10.03.21 23:00 Follicular regulatory T cells produce neuritin to regulate B cells

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Follicular regulatory T cells produce an abundance of neuritin protein, which acts directly on B cells to suppress B cell-driven autoimmunity and IgE-mediated allergies.

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09.03.21 23:00 Dissecting the contribution of host genetics and the microbiome in complex behaviors

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Host genetics and the microbiome interdependently regulate maladaptive behaviors in a mouse model for neurodevelopmental disorders. Additionally, precise microbial therapy, or microbe-induced metabolite-based therapy, selectively rescues social deficits but not hyperactivity.

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03.03.21 23:00 Conserved pleiotropy of an ancient plant homeobox gene uncovered by cis-regulatory dissection

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Functional dissections of cis-regulatory DNA suggest a conserved hidden pleiotropy widespread in plant evolution that has implications for the utilization of genome editing in agriculture

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01.03.21 23:00 Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin-angiotensin system

Using an infection-permissive human kidney cell line, Yeung et al. show that a soluble form of ACE2 that is cleaved and liberated from the host cell surface mediates SARS-CoV-2 binding and uptake by receptors involved in renin-angiotensin system signaling.

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22.02.21 23:00 A trans-complementation system for SARS-CoV-2 recapitulates authentic viral replication without virulence

Zhang et al. develop a trans-complementation system to produce single-round infectious SARS-CoV-2 that recapitulates authentic viral infection and replication. They then show the system can be safely used at biosafety level 2 for high-throughput antiviral testing.

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22.02.21 23:00 SARS-CoV-2 501Y.V2 variants lack higher infectivity but do have immune escape

Experiments with pseudotyped viruses show that the 501Y.V2 variant of SARS-CoV-2 exhibits resistance to neutralization from monoclonal antibodies and sera from convalescent as well as immunized individuals, predominantly due to the E484K and N501Y mutations in the receptor-binding domain of the viral spike protein.

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22.02.21 23:00 Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera

Structure-function analysis of the SARS-CoV-2 variant B.1.351 using serum samples from convalescent and vaccinated individuals reveals how mutations in the viral spike protein result in tighter binding to the receptor ACE2 and allow escape from monoclonal antibody neutralization.

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22.02.21 23:00 Extremely potent human monoclonal antibodies from COVID-19 convalescent patients

Schlagwörter: Expanding, Wellcome

Extremely potent neutralizing human monoclonal antibodies, though rare, are isolated from COVID-19 convalescent patients and suitable for prophylactic and therapeutic interventions of wild-type SARS-CoV-2 as well as emerging variants.

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17.02.21 23:00 Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera

The SARS-CoV-2 B.1.1.7 variant is not neutralized as easily as the original form of the virus. Some public antibodies cannot neutralize B.1.1.7, due to altered light-chain contacts with residue 501. However, B.1.1.7 does not show widespread escape from monoclonal antibodies, natural antibody responses, or vaccines.

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17.02.21 23:00 The antigenic anatomy of SARS-CoV-2 receptor binding domain

Dejnirattisai et al. present an in-depth study of the human antibody response to SARS-CoV-2 infection. By characterizing 377 human mAbs from recovered COVID-19 patients, and determining 19 protein structures, they construct a map of antibody footprints on the RBD describe in great detail its antigenic anatomy.

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15.02.21 23:00 COVID-19 and the human innate immune system

Differences in innate immune system function may underpin the curiously variable disease spectrum of COVID-19.

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