Philippe J. Sansonetti

Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur

Affiliated withInstitut Pasteur Collège de France Institut Pasteur Shanghai and Chinese Academy of Sciences

Research Area

Immunology and InfectionBiology

Biography

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JoVE Journal Publications

ArticleTotal : 2	Year
Publication title	2017
Publication title	2021

Other Publications

Article	Year
Immunogenicity of IpaC-hybrid proteins expressed in the Shigella flexneri 2a vaccine candidate SC602. Infection and immunity\| PubMed ID: 9423842	1998
Trafficking of Shigella lipopolysaccharide in polarized intestinal epithelial cells. The Journal of cell biology\| PubMed ID: 10330399	1999
Vaccination against shigellosis with attenuated Shigella flexneri 2a strain SC602. Infection and immunity\| PubMed ID: 10377124	1999
Activation of the CDC42 effector N-WASP by the Shigella flexneri IcsA protein promotes actin nucleation by Arp2/3 complex and bacterial actin-based motility. The Journal of cell biology\| PubMed ID: 10491394	1999
Increased interleukin-1 (IL-1) and imbalance between IL-1 and IL-1 receptor antagonist during acute inflammation in experimental Shigellosis. Infection and immunity\| PubMed ID: 10531267	1999
Induction of necrosis in human neutrophils by Shigella flexneri requires type III secretion, IpaB and IpaC invasins, and actin polymerization. Infection and immunity\| PubMed ID: 10678940	2000
Parameters underlying successful protection with live attenuated mutants in experimental shigellosis. Infection and immunity\| PubMed ID: 11160004	2001
CARD4/Nod1 mediates NF-kappaB and JNK activation by invasive Shigella flexneri. EMBO reports\| PubMed ID: 11463746	2001
Predominance of serotype-specific mucosal antibody response in Shigella flexneri-infected humans living in an area of endemicity. Infection and immunity\| PubMed ID: 11500390	2001
Intracellular vs extracellular recognition of pathogens--common concepts in mammals and flies. Trends in microbiology\| PubMed ID: 11912027	2002
Two msbB genes encoding maximal acylation of lipid A are required for invasive Shigella flexneri to mediate inflammatory rupture and destruction of the intestinal epithelium. Journal of immunology (Baltimore, Md. : 1950)\| PubMed ID: 11994481	2002
Apoptosis in acute shigellosis is associated with increased production of Fas/Fas ligand, perforin, caspase-1, and caspase-3 but reduced production of Bcl-2 and interleukin-2. Infection and immunity\| PubMed ID: 12011015	2002
The contribution of accessory toxins of Vibrio cholerae O1 El Tor to the proinflammatory response in a murine pulmonary cholera model. The Journal of experimental medicine\| PubMed ID: 12045243	2002
Human monocytes kill Shigella flexneri but then die by apoptosis associated with suppression of proinflammatory cytokine production. Infection and immunity\| PubMed ID: 12065527	2002
Conversion of PtdIns(4,5)P(2) into PtdIns(5)P by the S.flexneri effector IpgD reorganizes host cell morphology. The EMBO journal\| PubMed ID: 12356723	2002
Identification of the cis-acting site involved in activation of promoters regulated by activity of the type III secretion apparatus in Shigella flexneri. Journal of bacteriology\| PubMed ID: 12446624	2002
Gene-environment interaction modulated by allelic heterogeneity in inflammatory diseases. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 12626759	2003
Shigella interaction with intestinal epithelial cells determines the innate immune response in shigellosis. International journal of medical microbiology : IJMM\| PubMed ID: 12755366	2003
Nod1 detects a unique muropeptide from gram-negative bacterial peptidoglycan. Science (New York, N.Y.)\| PubMed ID: 12791997	2003
The invasive phenotype of Shigella flexneri directs a distinct gene expression pattern in the human intestinal epithelial cell line Caco-2. The Journal of biological chemistry\| PubMed ID: 12813033	2003
Anti-inflammatory role for intracellular dimeric immunoglobulin a by neutralization of lipopolysaccharide in epithelial cells. Immunity\| PubMed ID: 12818156	2003
Peptidoglycan molecular requirements allowing detection by Nod1 and Nod2. The Journal of biological chemistry\| PubMed ID: 12871942	2003
Bacterial invasion: the paradigms of enteroinvasive pathogens. Science (New York, N.Y.)\| PubMed ID: 15073367	2004
Cortactin and Crk cooperate to trigger actin polymerization during Shigella invasion of epithelial cells. The Journal of cell biology\| PubMed ID: 15263018	2004
IL-8 is a key chemokine regulating neutrophil recruitment in a new mouse model of Shigella-induced colitis. Journal of immunology (Baltimore, Md. : 1950)\| PubMed ID: 15356171	2004
Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island. Nature immunology\| PubMed ID: 15489856	2004
War and peace at mucosal surfaces. Nature reviews. Immunology\| PubMed ID: 15573130	2004
Adherence modifies the regulation of gene expression induced by interleukin-10. Cytokine\| PubMed ID: 15579372	2005
Apical invasion of intestinal epithelial cells by Salmonella typhimurium requires villin to remodel the brush border actin cytoskeleton. Cell host & microbe\| PubMed ID: 25600187	2015
The Shigella flexneri effector OspG interferes with innate immune responses by targeting ubiquitin-conjugating enzymes. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 16162672	2005
Identification of the critical residues involved in peptidoglycan detection by Nod1. The Journal of biological chemistry\| PubMed ID: 16172124	2005
Murine Nod1 but not its human orthologue mediates innate immune detection of tracheal cytotoxin. EMBO reports\| PubMed ID: 16211083	2005
Magnetic resonance imaging of Klebsiella pneumoniae-induced pneumonia in mice. Cellular microbiology\| PubMed ID: 16367864	2006
PtdIns5P activates the host cell PI3-kinase/Akt pathway during Shigella flexneri infection. The EMBO journal\| PubMed ID: 16482216	2006
Shigellosis: an old disease in new clothes? PLoS medicine\| PubMed ID: 16968125	2006
The bacterial weaponry: lessons from Shigella. Annals of the New York Academy of Sciences\| PubMed ID: 17057210	2006
The innate signaling of dangers and the dangers of innate signaling. Nature immunology\| PubMed ID: 17110939	2006
An injected bacterial effector targets chromatin access for transcription factor NF-kappaB to alter transcription of host genes involved in immune responses. Nature immunology\| PubMed ID: 17159983	2007
Sensing of bacteria: NOD a lonely job. Current opinion in microbiology\| PubMed ID: 17161646	2007
Shigella's ways of manipulating the host intestinal innate and adaptive immune system: a tool box for survival? Immunology and cell biology\| PubMed ID: 17213832	2007
Capping of actin filaments by vinculin activated by the Shigella IpaA carboxyl-terminal domain. FEBS letters\| PubMed ID: 17289036	2007
Debugging how bacteria manipulate the immune response. Immunity\| PubMed ID: 17307704	2007
The pattern-recognition molecule Nod1 is localized at the plasma membrane at sites of bacterial interaction. Cellular microbiology\| PubMed ID: 17970764	2008
Type III secretion effectors of the IpaH family are E3 ubiquitin ligases. Cell host & microbe\| PubMed ID: 18005683	2007
Epigenetic regulation of host response to LPS: causing tolerance while avoiding Toll errancy. Cell host & microbe\| PubMed ID: 18005703	2007
Molecular and cellular bases of bacterial virulence: guessing the future episodes of an ongoing saga. Research in microbiology\| PubMed ID: 18162373	2008
Cytoplasmic targeting of IpaC to the bacterial pole directs polar type III secretion in Shigella. The EMBO journal\| PubMed ID: 18188151	2008
Phase 1 clinical trial of live attenuated Shigella dysenteriae type-1 DeltaicsA Deltaent Deltafep DeltastxA:HgR oral vaccine SC599 in healthy human adult volunteers. Vaccine\| PubMed ID: 18207287	2008
Rupture, invasion and inflammatory destruction of the intestinal barrier by Shigella: the yin and yang of innate immunity. The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale\| PubMed ID: 18418486	2006
Virulent Shigella flexneri subverts the host innate immune response through manipulation of antimicrobial peptide gene expression. The Journal of experimental medicine\| PubMed ID: 18426984	2008
Host-bacteria homeostasis in the healthy and inflamed gut. Current opinion in gastroenterology\| PubMed ID: 18622156	2008
Vaccination against shigellosis: is it the path that is difficult or is it the difficult that is the path? Microbes and infection\| PubMed ID: 18672087	2008
Structure of the Shigella T3SS effector IpaH defines a new class of E3 ubiquitin ligases. Nature structural & molecular biology\| PubMed ID: 18997778	2008
The IpaC carboxyterminal effector domain mediates Src-dependent actin polymerization during Shigella invasion of epithelial cells. PLoS pathogens\| PubMed ID: 19165331	2009
A synthetic carbohydrate-protein conjugate vaccine candidate against Shigella flexneri 2a infection. Journal of immunology (Baltimore, Md. : 1950)\| PubMed ID: 19201878	2009
Characterisation of early mucosal and neuronal lesions following Shigella flexneri infection in human colon. PloS one\| PubMed ID: 19274103	2009
Learning tolerance while fighting ignorance. Cell\| PubMed ID: 19665961	2009
Framing a concept and an agenda for infectious diseases in EMBO Molecular Medicine. EMBO molecular medicine\| PubMed ID: 20049719	2009
Breathing life into pathogens: the influence of oxygen on bacterial virulence and host responses in the gastrointestinal tract. Cellular microbiology\| PubMed ID: 21166974	2011
Antigen-specific CD8(+) T cells fail to respond to Shigella flexneri. Infection and immunity\| PubMed ID: 21357720	2011
The Shigella flexneri type three secretion system effector IpgD inhibits T cell migration by manipulating host phosphoinositide metabolism. Cell host & microbe\| PubMed ID: 21501826	2011
ATP-mediated Erk1/2 activation stimulates bacterial capture by filopodia, which precedes Shigella invasion of epithelial cells. Cell host & microbe\| PubMed ID: 21669399	2011
Design of a specific colonic mucus marker using a human commensal bacterium cell surface domain. The Journal of biological chemistry\| PubMed ID: 22427651	2012
Characterization of the promoter, MxiE box and 5' UTR of genes controlled by the activity of the type III secretion apparatus in Shigella flexneri. PloS one\| PubMed ID: 22427898	2012
A crypt-specific core microbiota resides in the mouse colon. mBio\| PubMed ID: 22617141	2012
Quantitative RT-PCR profiling of the rabbit immune response: assessment of acute Shigella flexneri infection. PloS one\| PubMed ID: 22675469	2012
Shigella effector IpaB-induced cholesterol relocation disrupts the Golgi complex and recycling network to inhibit host cell secretion. Cell host & microbe\| PubMed ID: 22980334	2012
[Acute intestinal infections: current and upcoming vaccines]. Presse medicale (Paris, France : 1983)\| PubMed ID: 23237786	2013
Shigella impairs T lymphocyte dynamics in vivo. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 23417297	2013
A novel murine model of rhinoscleroma identifies Mikulicz cells, the disease signature, as IL-10 dependent derivatives of inflammatory monocytes. EMBO molecular medicine\| PubMed ID: 23554169	2013
Epithelial cell proliferation arrest induced by lactate and acetate from Lactobacillus casei and Bifidobacterium breve. PloS one\| PubMed ID: 23646174	2013
Virulent Shigella flexneri affects secretion, expression, and glycosylation of gel-forming mucins in mucus-producing cells. Infection and immunity\| PubMed ID: 23876800	2013
Microbiota and the immune system, an amazing mutualism forged by co-evolution. Seminars in immunology\| PubMed ID: 24269722	2013
A Shigella effector dampens inflammation by regulating epithelial release of danger signal ATP through production of the lipid mediator PtdIns5P. Immunity\| PubMed ID: 24332032	2013
A fluorescent reporter reveals on/off regulation of the Shigella type III secretion apparatus during entry and cell-to-cell spread. Cell host & microbe\| PubMed ID: 24528864	2014
ZapE is a novel cell division protein interacting with FtsZ and modulating the Z-ring dynamics. mBio\| PubMed ID: 24595368	2014
New insights into the crosstalk between Shigella and T lymphocytes. Trends in microbiology\| PubMed ID: 24613405	2014
The lacdiNAc-specific adhesin LabA mediates adhesion of Helicobacter pylori to human gastric mucosa. The Journal of infectious diseases\| PubMed ID: 24755437	2014
Non-stoichiometric O-acetylation of Shigella flexneri 2a O-specific polysaccharide: synthesis and antigenicity. Organic & biomolecular chemistry\| PubMed ID: 24836582	2014
Tracking bacterial pathogens with genetically-encoded reporters. FEBS letters\| PubMed ID: 24859085	2014
B lymphocytes undergo TLR2-dependent apoptosis upon Shigella infection. The Journal of experimental medicine\| PubMed ID: 24863068	2014
The cytosolic bacterial peptidoglycan sensor Nod2 affords stem cell protection and links microbes to gut epithelial regeneration. Cell host & microbe\| PubMed ID: 24882705	2014
Functional genomics of Lactobacillus casei establishment in the gut. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 25024222	2014
Rapid 96-well plates DNA extraction and sequencing procedures to identify genome-wide transposon insertion sites in a difficult to lyse bacterium: Lactobacillus casei. Journal of microbiological methods\| PubMed ID: 25135488	2014
The cofilin phosphatase slingshot homolog 1 (SSH1) links NOD1 signaling to actin remodeling. PLoS pathogens\| PubMed ID: 25187968	2014
Type III secretion system. Current biology : CB\| PubMed ID: 25202865	2014
TOM1 is a PI5P effector involved in the regulation of endosomal maturation. Journal of cell science\| PubMed ID: 25588840	2015
Growth and host interaction of mouse segmented filamentous bacteria in vitro. Nature\| PubMed ID: 25600271	2015
Pathogen manipulation of B cells: the best defence is a good offence. Nature reviews. Microbiology\| PubMed ID: 25659322	2015
An O antigen capsule modulates bacterial pathogenesis in Shigella sonnei. PLoS pathogens\| PubMed ID: 25794007	2015
Mucosal physical and chemical innate barriers: Lessons from microbial evasion strategies. Seminars in immunology\| PubMed ID: 25936225	2015
Functional Genomic Screen Identifies Klebsiella pneumoniae Factors Implicated in Blocking Nuclear Factor κB (NF-κB) Signaling. The Journal of biological chemistry\| PubMed ID: 25971969	2015
Escape of Actively Secreting Shigella flexneri from ATG8/LC3-Positive Vacuoles Formed during Cell-To-Cell Spread Is Facilitated by IcsB and VirA. mBio\| PubMed ID: 26015503	2015
Bioimage analysis of Shigella infection reveals targeting of colonic crypts. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 26056271	2015
Diet and specific microbial exposure trigger features of environmental enteropathy in a novel murine model. Nature communications\| PubMed ID: 26241678	2015
Draft Genome Sequences of Acinetobacter parvus CM11, Acinetobacter radioresistens CM38, and Stenotrophomonas maltophilia BR12, Isolated from Murine Proximal Colonic Tissue. Genome announcements\| PubMed ID: 26472823	2015
PI5P Triggers ICAM-1 Degradation in Shigella Infected Cells, Thus Dampening Immune Cell Recruitment. Cell reports\| PubMed ID: 26776508	2016
A Synthetic Carbohydrate Conjugate Vaccine Candidate against Shigellosis: Improved Bioconjugation and Impact of Alum on Immunogenicity. Bioconjugate chemistry\| PubMed ID: 26918643	2016
Shigella Diversity and Changing Landscape: Insights for the Twenty-First Century. Frontiers in cellular and infection microbiology\| PubMed ID: 27148494	2016
Histone deacetylase inhibition enhances antimicrobial peptide but not inflammatory cytokine expression upon bacterial challenge. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 27162363	2016
Shigella flexneri modulates stress granule composition and inhibits stress granule aggregation. Cellular microbiology\| PubMed ID: 27282465	2016
Anoxia and glucose supplementation preserve neutrophil viability and function. Blood\| PubMed ID: 27402974	2016
Intestinal Organoids as a Novel Tool to Study Microbes-Epithelium Interactions. Methods in molecular biology (Clifton, N.J.)\| PubMed ID: 27628134	2016
High-fat diet modifies the PPAR-γ pathway leading to disruption of microbial and physiological ecosystem in murine small intestine. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 27638207	2016
From homeostasis to pathology: decrypting microbe-host symbiotic signals in the intestinal crypt. Philosophical transactions of the Royal Society of London. Series B, Biological sciences\| PubMed ID: 27672151	2016
Multifaceted Functions of NOD-Like Receptor Proteins in Myeloid Cells at the Intersection of Innate and Adaptive Immunity. Microbiology spectrum\| PubMed ID: 27726775	2016
The infectious hypoxia: occurrence and causes during Shigella infection. Microbes and infection\| PubMed ID: 27884799	2017
Complete Genome Sequence of Delftia tsuruhatensis CM13 Isolated from Murine Proximal Colonic Tissue. Genome announcements\| PubMed ID: 27979948	2016
[Microbiota-intestinal stem cells dialog: a key element for intestinal regeneration]. Medecine sciences : M/S\| PubMed ID: 28008839	2016
CD34+ mesenchymal cells are a major component of the intestinal stem cells niche at homeostasis and after injury. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 28074039	2017
Candidate immune biomarkers for radioimmunotherapy. Biochimica et biophysica acta\| PubMed ID: 28254528	2017
Moving molecular medicine. EMBO molecular medicine\| PubMed ID: 28314782	2017
Threonine eliminylation by bacterial phosphothreonine lyases rapidly causes cross-linking of mitogen-activated protein kinase (MAPK) in live cells. The Journal of biological chemistry\| PubMed ID: 28325837	2017
Segmented filamentous bacteria, Th17 inducers and helpers in a hostile world. Current opinion in microbiology\| PubMed ID: 28453971	2017
Impact of high-fat diet on the intestinal microbiota and small intestinal physiology before and after the onset of obesity. Biochimie\| PubMed ID: 28571979	2017
Shigella sonnei Encodes a Functional T6SS Used for Interbacterial Competition and Niche Occupancy. Cell host & microbe\| PubMed ID: 28618272	2017
Comparative genomic analysis of Acinetobacter strains isolated from murine colonic crypts. BMC genomics\| PubMed ID: 28697749	2017
Injection of T3SS effectors not resulting in invasion is the main targeting mechanism of toward human lymphocytes. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 28847968	2017
Lipopolysaccharide from Crypt-Specific Core Microbiota Modulates the Colonic Epithelial Proliferation-to-Differentiation Balance. mBio\| PubMed ID: 29042502	2017
Identification of novel substrates of Shigella T3SA through analysis of its virulence plasmid-encoded secretome. PloS one\| PubMed ID: 29073283	2017
Editorial: Editorial for the virtual issue on microbiome. FEMS microbiology reviews\| PubMed ID: 29228184	2018
Colorectal cancer specific conditions promote gut colonization. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 29279402	2018
Pathogens, microbiome and the host: emergence of the ecological Koch's postulates. FEMS microbiology reviews\| PubMed ID: 29325027	2018
Rhinoscleroma pathogenesis: The type K3 capsule of Klebsiella rhinoscleromatis is a virulence factor not involved in Mikulicz cells formation. PLoS neglected tropical diseases\| PubMed ID: 29381692	2018
Host Cell Targeting by Enteropathogenic Bacteria T3SS Effectors. Trends in microbiology\| PubMed ID: 29477730	2018
MUB Binds to Lactoferrin and Stands as a Specific Neutrophil Marker. Cell chemical biology\| PubMed ID: 29478905	2018
Measles 2018: a tale of two anniversaries. EMBO molecular medicine\| PubMed ID: 29685959	2018
Human Enteric α-Defensin 5 Promotes Shigella Infection by Enhancing Bacterial Adhesion and Invasion. Immunity\| PubMed ID: 29858013	2018
Identifying the etiology and pathophysiology underlying stunting and environmental enteropathy: study protocol of the AFRIBIOTA project. BMC pediatrics\| PubMed ID: 30025542	2018
Stunted childhood growth is associated with decompartmentalization of the gastrointestinal tract and overgrowth of oropharyngeal taxa. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 30126990	2018
Disentangling Host-Microbiota Regulation of Lipid Secretion by Enterocytes: Insights from Commensals and . mBio\| PubMed ID: 30181250	2018
Shigella and Enteroinvasive Escherichia Coli. Current topics in microbiology and immunology\| PubMed ID: 30218158	2018
Natural molecules induce and synergize to boost expression of the human antimicrobial peptide β-defensin-3. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 30275324	2018
Expression of the human antimicrobial peptide β-defensin-1 is repressed by the EGFR-ERK-MYC axis in colonic epithelial cells. Scientific reports\| PubMed ID: 30575780	2018
Pathogenesis: New Insights through Advanced Methodologies. Microbiology spectrum\| PubMed ID: 30953429	2019
-mediated immunosuppression in the human gut: subversion extends from innate to adaptive immune responses. Human vaccines & immunotherapeutics\| PubMed ID: 30964713	2019
promotes major alteration of gut epithelial physiology and tissue invasion by shutting off host intracellular transport. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 31209035	2019
Crypt- and Mucosa-Associated Core Microbiotas in Humans and Their Alteration in Colon Cancer Patients. mBio\| PubMed ID: 31311881	2019
Shigella-mediated oxygen depletion is essential for intestinal mucosa colonization. Nature microbiology\| PubMed ID: 31383999	2019
Mapping of Shigella flexneri's tissue distribution and type III secretion apparatus activity during infection of the large intestine of guinea pigs. Pathogens and disease\| PubMed ID: 31578543	2019
Colorectal cancer-associated microbiota contributes to oncogenic epigenetic signatures. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 31712445	2019
Intracellular offspring released from SFB filaments are flagellated. Nature microbiology\| PubMed ID: 31819216	2020
Innate immune receptor NOD2 mediates LGR5 intestinal stem cell protection against ROS cytotoxicity via mitophagy stimulation. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 31919280	2020
Shigella impairs human T lymphocyte responsiveness by hijacking actin cytoskeleton dynamics and T cell receptor vesicular trafficking. Cellular microbiology\| PubMed ID: 31957253	2020
Fermentation Products of Commensal Bacteria Alter Enterocyte Lipid Metabolism. Cell host & microbe\| PubMed ID: 32101704	2020
Study of the Operon Coding a Two-Component System and a Putative L,D-Carboxypeptidase in . Frontiers in microbiology\| PubMed ID: 32194510	2020
COVID-19, chronicle of an expected pandemic. EMBO molecular medicine\| PubMed ID: 32259394	2020
Immunoglobulin recognition of fecal bacteria in stunted and non-stunted children: findings from the Afribiota study. Microbiome\| PubMed ID: 32718353	2020
Survival of the Wealthiest? The EMBO journal\| PubMed ID: 33205839	2020
High prevalence of intestinal parasite infestations among stunted and control children aged 2 to 5 years old in two neighborhoods of Antananarivo, Madagascar. PLoS neglected tropical diseases\| PubMed ID: 33878113	2021
Structural Insights of Translocator IpaB and Its Chaperone IpgC in Solution. Frontiers in cellular and infection microbiology\| PubMed ID: 33996640	2021
Vitamin C levels in a Central-African mother-infant cohort: Does hypovitaminosis C increase the risk of enteric infections? Maternal & child nutrition\| PubMed ID: 34137176	2021
Cytokine receptor cluster size impacts its endocytosis and signaling. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 34504012	2021