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Microbial Immunology and Immunogenetics

Research Lines

Content with Investigacion Entomología Médica .

The Laboratory of Medical Entomology (LME) develops an intense reference and research activity, focused on the field of disease vectors of interest in Public Health. The LME has an insectary where biological cycles of insect vectors are currently maintained, allowing the performance, among others, of vector competence and xenodiagnostic studies. The LME supports the national health system by offering techniques available in the portfolio of services for the taxonomic identification of arthropods of health interest. In addition, it performs entomological surveillance of outbreaks, supporting Surveillance Plans. In particular, the LME plays a leading role in the Entomological Surveillance Plan for Leishmaniasis in the Community of Madrid. On the other hand, the LME offers scientific advice to the CCAES (Centro de Coordinación de Alertas y Emergencias Sanitarias, Ministerio de Sanidad, Consumo y Bienestar Social), and participates in the elaboration of reports and rapid risk assessments.


 

The main research lines of the Laboratory of Medical Entomology are:

1. Maintenance of insect vector colonies: phlebotomine sand flies (Phlebotomus perniciosus, Phlebotomus papatasi and Phlebotomus argentipes, vectors of Leishmania infantum, Leishmania major and Leishmania donovani, respectively), Culex and Aedes mosquitoes (vectors of various arboviruses) and Rhodnius prolixus (vector of Trypanosoma cruzi). 
2. Biology of disease vectors of public health interest: biology, vector competence, experimental infections. The CNM has a BSL3 safety laboratory to carry out vector competence studies with culicidae and phlebotomine sand flies.
3. Entomological sampling, infectivity of potential reservoirs of leishmaniasis.
4. Insecticides and repellents: evaluation of their efficacy. 
5. Characterization of saliva proteins of hematophagous Diptera: genomics, proteomics, biochemistry and gene editing. Study of salivary proteins as markers of bite exposure, virulence factors and/or vaccines.
6. Xenodiagnosis of leishmaniasis.
7. Molecular biology and taxonomy of phlebotomine sand flies. Molecular detection of Leishmania infantum in phlebotomine sand flies and characterization of Leishmania spp. Molecular identification of blood ingested by vectors.

Research projects

Content with Investigacion Entomología Médica .

CURRENT PROJECTS

Project title: "Biochemical and functional characterisation of salivary proteins of Phlebotomus perniciosus and their role in infection by Leishmania infantum (PERNIPROT)"
Reference: Project PID2023-147773NA-I00 funded by MICIU/AEI/10.13039/501100011033 and by FEDER, EU.
Start date: 01/09/2024
End date: 31/08/2028
Funding: €175,000
Principal investigator: Inés Elena Martín Martín. 
Funding agency: Agencia Estatal de Investigación (Proyecto de Generación del Conocimiento 2023).


 

Project title: "Surveillance of leishmaniasis in the Community of Madrid from a “One Health” perspective: study of the infectious capacity of patients with visceral leishmaniasis and their role as reservoirs"
Reference: PI24CIII/00026
Start date: 01/01/2025
End date: 31/12/2027
Funding: €60,000.00
Principal investigator: Inés Elena Martín Martín. 
Co-principal investigator: Maribel Jiménez Alonso
Funding agency: Instituto de Salud Carlos III (Strategic Action in Intramural Health, AESI). 

Service Contract: "Analysis for the surveillance of the vector and wild reservoirs that transmit leishmaniasis in the Community of Madrid"
Reference: file no. 17/2024 (A/SER-008455/2024).
Start date: 26/06/2024
End date: 10/12/25, extendable to 2026
Total funding: €171,084
Principal Investigator: Maribel Jiménez Alonso
Funding agency: Service Contract between the Instituto de Salud Carlos III and the Directorate-General for Public Health, Regional Ministry of Health of the Community of Madrid 

Project Title: CIBERINFEC Research Group (CB21/13/00110)
Start date: 2021
End date: currently active
Principal Investigator: Dr. Mª Paz Sánchez-Seco, Arbovirus and Imported Viral Diseases Unit. 
Researchers from the Medical Entomology Laboratory: Maribel Jiménez (member), Inés Martín Martín (collaborator).
Funding: €108,134. File number: CB21/13/00110.
Funding agency: Consortium Centre for Biomedical Research in NETWORK (CIBER)


 

PAST PROJECTS

Service Contract: "Evaluation of the anti-leishmania effect of the bacteria Tc1 and its derivatives in the intravectorial cycle"
Reference: ISCIII-06896
Start date: 15/12/2022
End date: 15/04/2025
Funding: €71,265.67
Principal Investigator: Inés Elena Martín Martín
Funding agency: Service Contract between the company GlaxoSmithKline R&D (GSK) and the Instituto de Salud Carlos III

Service Contract: "Analysis for the surveillance of the vector and wild reservoirs that transmit leishmaniasis in the Community of Madrid"
Reference: 59/2020 (A/SER-040739/2020)
Start date: 10/12/2021
End date: 10/12/2023.   
Funding: €42,612.17 per year   Total 2021-2023: €127,836.51
Principal Investigators: Ricardo Molina /Maribel Jiménez Alonso
Funding agency: Service contract between the Instituto de Salud Carlos III (ISCIII) and the Directorate-General for Public Health, Regional Ministry of Health of the Community of Madrid

Project title: "Research and Integrated Surveillance of Emerging Arboviruses West Nile, Toscana and Dengue in some areas of Spain"
Reference: PI19CIII/00014
Start date: 2020
End date: 2022
Principal Investigator: Ana Vázquez González
Co-Principal Investigator: Ricardo Molina
Funding: €60,000.00
Funding agency: Instituto de Salud Carlos III (Strategic Action in Intramural Health, AESI).

Project title: "Characterisation of the concept of ‘asymptomatic carrier’ in leishmaniasis: implications for treatment".
Start date: 01/01/2015
End date: 31/12/2017
Principal investigators: Javier Moreno and Javier García
Funding: €159,940
Funding agency: Study Agreement between Drugs for Neglected Diseases Initiative (DNDi), the Spanish Foundation for International Cooperation, Health and Social Policy (FCSAI) and Fuenlabrada Hospital. Subcontractor: ISCIII Medical Entomology Unit (Maribel Jiménez and Ricardo Molina).

Project title: "Biology and control of vector-borne infections in Europe (EDENext Collaborative Project): Sandfly-borne diseases".  
Reference: Subproject (PBD) (EU, FP7-HEALTH-2010-single-stage, contract No. 261504).
Start date: 2011
End date: 2014
Principal investigator: Ricardo Molina     General coordinator: Petr Volf
Funding: €140,000
Funding agency: EU-FP7

Project Title: "Phlebotomus perniciosus saliva as a source in the search for potential targets for the development of vaccines against Leishmania infantum"
Reference: AGL2008-01592/GAN (MICINN)
Start date: 2009
End date: 2011
Principal investigator: Ricardo Molina
Funding: €70,180
Funding agency: Ministry of Science and Innovation

Publications

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Botulism in Spain: Epidemiology and Outcomes of Antitoxin Treatment, 1997-2019

Peñuelas M, Guerrero-Vadillo M, Valdezate S, Zamora MJ, Leon-Gomez I, Flores-Cuéllar Á, Carrasco G, Díaz-García O, Varela C. (2022). Botulism in Spain: Epidemiology and Outcomes of Antitoxin Treatment, 1997-2019. Toxins (Basel). 20;15(1):2

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Invasive Streptococcus pyogenes disease in Spain: a microbiological and epidemiological study covering the period 2007-2019

Villalón P, Sáez-Nieto JA, Rubio-López V, Medina-Pascual MJ, Garrido N, Carrasco G, Pino-Rosa S, Valdezate S. (2021). Invasive Streptococcus pyogenes disease in Spain: a microbiological and epidemiological study covering the period 2007-2019. Eur J Clin Microbiol Infect Dis. 2021 Nov;40(11):2295-2303

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ANISERP: a new serpin from the parasite Anisakis simplex.

Valdivieso E, Perteguer MJ, Hurtado C, Campioli P, Rodríguez E, Saborido A, Martínez-Sernández V, Gómez-Puertas P, Ubeira FM, Gárate T. ANISERP: a new serpin from the parasite Anisakis simplex.Parasit Vectors. 2015 Jul 28;8:399.

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Revisiting the Ancylostoma caninum secretome provides new information on hookworm-host interactions.

Morante T, Shepherd C, Constantinoiu C, Loukas A, Sotillo J. Revisiting the Ancylostoma caninum secretome provides new information on hookworm-host interactions. Proteomics. 2017 Dec;17(23-24).

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Hookworm secreted extracellular vesicles interact with host cells and prevent inducible colitis in mice.

Eichenberger RM, Ryan S, Jones L, Buitrago G, Polster R, Montes de Oca M, Zuvelek J, Giacomin PR, Dent LA, Engwerda CR, Field MA, Sotillo J, Loukas A. Hookworm secreted extracellular vesicles interact with host cells and prevent inducible colitis in mice. Front Immunol. 2018 Apr 30;9:850.

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HDP2: a ribosomal DNA (NTS-ETS) sequence as a target for species-specific molecular diagnosis of intestinal taeniasis in humans.

Flores MD, Gonzalez LM, Hurtado C, Motta YM, Domínguez-Hidalgo C, Merino FJ, Perteguer MJ, Gárate T. HDP2: a ribosomal DNA (NTS-ETS) sequence as a target for species-specific molecular diagnosis of intestinal taeniasis in humans. Parasit Vectors. 2018 Feb 27;11(1):117. doi: 10.1186/s13071-018-2646-6.

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Antibody responses to chimeric peptides derived from parasite antigens in mice and other animal species.

Orbegozo-Medina RA, Martínez-Sernández V, Folgueira I, Mezo M, González-Warleta M, Perteguer MJ, Romarís F, Leiro JM, Ubeira FM. Antibody responses to chimeric peptides derived from parasite antigens in mice and other animal species. Mol Immunol. 2018 Dec 17;106:1-11.

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Comparison of T24H-his, GST-T24H and GST-Ts8B2 recombinant antigens in western blot, ELISA and multiplex bead-based assay for diagnosis of neurocysticercosis.

Hernández-González A, Noh J, Perteguer MJ, Gárate T, Handali S. Comparison of T24H-his, GST-T24H and GST-Ts8B2 recombinant antigens in western blot, ELISA and multiplex bead-based assay for diagnosis of neurocysticercosis. Parasit Vectors. 2017 May 15;10(1):237.

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Characterization of Trichuris muris secreted proteins and extracellular vesicles provides new insights into host-parasite communication.

Eichenberger RM, Talukder MH, Field MA, Wangchuk P, Giacomin P, Loukas A, Sotillo J. Characterization of Trichuris muris secreted proteins and extracellular vesicles provides new insights into host-parasite communication. J Extracell Vesicles. 2018 Jan 21;7(1):1428004.

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Evaluation of onchocerciasis seroprevalence in Bioko Island (Equatorial Guinea) after years of disease control programmes.

Hernández-González A, Moya L, Perteguer MJ, Herrador Z, Nguema R, Nguema J, Aparicio P, Benito A, Gárate T. Evaluation of onchocerciasis seroprevalence in Bioko Island (Equatorial Guinea) after years of disease control programmes. Parasit Vectors. 2016 Sep 20;9(1):509.

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Changes in protein expression after treatment with Ancylostoma caninum excretory/secretory products in a mouse model of colitis.

Sotillo J, Ferreira I, Potriquet J, Laha T, Navarro S, Loukas A, Mulvenna J. Changes in protein expression after treatment with Ancylostoma caninum excretory/secretory products in a mouse model of colitis. Sci Rep. 2017 Feb 13;7:41883.

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Fasciola spp: Mapping of the MF6 epitope and antigenic analysis of the MF6p/HDM family of heme-binding proteins.

Martínez-Sernández V, Perteguer MJ, Mezo M, González-Warleta M, Gárate T, Valero MA, Ubeira FM. Fasciola spp: Mapping of the MF6 epitope and antigenic analysis of the MF6p/HDM family of heme-binding proteins. PLoS One. 2017 Nov 21;12(11):e0188520.

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Accumulation of endogenous free radicals is required to induce titan-like cell formation in Cryptococcus neoformans

Irene García-Barbazán, Alba Torres-Cano, Rocío García-Rodas, Martin Sachse, Daniel Luque, Diego Megías, Oscar Zaragoza. mBio. 2024 Jan 16;15(1):e0254923

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An alternative host model of a mixed fungal infection by azole susceptible and resistant Aspergillus spp strains

15. Alcazar-Fuoli L, Buitrago M, Gomez-Lopez A, Mellado E. An alternative host model of a mixed fungal infection by azole susceptible and resistant Aspergillus spp strains. Virulence. 2015;6(4):376-84. doi: 10.1080/21505594.2015.1025192. PMID: 26065322.

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Effect of pneumococcal conjugate vaccines and SARS-CoV-2 on antimicrobial resistance and the emergence of Streptococcus pneumoniae serotypes with reduced susceptibility in Spain, 2004-20: a national surveillance study

Sempere J, Llamosí M, López Ruiz B, Del Río I, Pérez-García C, Lago D, Gimeno M, Coronel P, González-Camacho F, Domenech M, Yuste J. Effect of pneumococcal conjugate vaccines and SARS-CoV-2 on antimicrobial resistance and the emergence of Streptococcus pneumoniae serotypes with reduced susceptibility in Spain, 2004-20: a national surveillance study. Lancet Microbe. 2022 Oct;3(10):e744-e752.

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Seconeolitsine, the Novel Inhibitor of DNA Topoisomerase I, Protects against Invasive Pneumococcal Disease Caused by Fluoroquinolone-Resistant Strains

Tirado-Vélez JM, Carreño D, Sevillano D, Alou L, Yuste J, de la Campa AG. Seconeolitsine, the Novel Inhibitor of DNA Topoisomerase I, Protects against Invasive Pneumococcal Disease Caused by Fluoroquinolone-Resistant Strains. Antibiotics. 2021 May 13;10(5):573.

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Minilungs from Human Embryonic Stem Cells to Study the Interaction of Streptococcus pneumoniae with the Respiratory Tract

Sempere J, Rossi SA, Chamorro-Herrero I, González-Camacho F, de Lucas MP, Rojas-Cabañeros JM, Taborda CP, Zaragoza Ó, Yuste J, Zambrano A. Minilungs from Human Embryonic Stem Cells to Study the Interaction of Streptococcus pneumoniae with the Respiratory Tract. Microbiol Spectr. 2022 Jun 29;10(3):e0045322

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A national longitudinal study evaluating the activity of cefditoren and other antibiotics against non-susceptible Streptococcus pneumoniae strains during the period 2004-20 in Spain

Sempere J, González-Camacho F, Domenech M, Llamosí M, Del Río I, López-Ruiz B, Gimeno M, Coronel P, Yuste J. A national longitudinal study evaluating the activity of cefditoren and other antibiotics against non-susceptible Streptococcus pneumoniae strains during the period 2004-20 in Spain. J Antimicrob Chemother. 2022 Mar 31;77(4):1045-1051.

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Nationwide Trends of Invasive Pneumococcal Disease in Spain From 2009 Through 2019 in Children and Adults During the Pneumococcal Conjugate Vaccine Era

de Miguel S, Domenech M, González-Camacho F, Sempere J, Vicioso D, Sanz JC, Comas LG, Ardanuy C, Fenoll A, Yuste J. Nationwide Trends of Invasive Pneumococcal Disease in Spain From 2009 Through 2019 in Children and Adults During the Pneumococcal Conjugate Vaccine Era. Clin Infect Dis. 2021 Dec 6;73(11):e3778-e3787

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Pulmonary BCG induces lung-resident macrophage activation and confers long-term protection against tuberculosis

7. Mata E, Tarancón R, Guerrero C, Moreo E, Moreau F, Uranga S, Gomez AB, Marinova D, Domenech M, Gonzalez-Camacho F, Monzon M, Badiola J, Dominguez-Andres J, Yuste J, Anel A, Peixoto A, Martin C, Aguilo N. Pulmonary BCG induces lung-resident macrophage activation and confers long-term protection against tuberculosis. Sci Immunol. 2021 Sep 24;6(63):eabc2934

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Vaccination with LytA, LytC, or Pce of Streptococcus pneumoniae Protects against Sepsis by Inducing IgGs That Activate the Complement System

Corsini B, Aguinagalde L, Ruiz S, Domenech M, Yuste J. Vaccination with LytA, LytC, or Pce of Streptococcus pneumoniae Protects against Sepsis by Inducing IgGs That Activate the Complement System. Vaccines. 2021 Feb 23;9(2):186.

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Physiologic and transcriptomic effects triggered by overexpression of wild type and mutant DNA topoisomerase I in Streptococcus pneumoniae

García-López M, Hernández P, Megias D, Ferrándiz MJ, de la Campa AG. Int J Mol Sci. 2023; 24:15800.

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StaR Is a positive regulator of topoisomerase I activity involved in supercoiling maintenance in Streptococcus pneumoniae

de Vasconcelos Junior AA, Tirado-Vélez JM, Martín-Galiano AJ, Megias D, Ferrándiz MJ, Hernández P, Amblar M, de la Campa AG. Int J Mol Sci. 2023; 24:5973.

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Role of PatAB transporter in efflux of levofloxacin in Streptococcus pneumoniae

Amblar M, Zaballos A, de la Campa AG. Antibiotics. 2022; 17:1837.

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Seconeolitsine, the novel inhibitor of DNA topoisomerase I, protects against invasive pneumococcal disease caused by fluoroquinolone-resistant strains.

Tirado-Vélez JM, Carreño D, Sevillano D, Alou L, Yuste J, de la Campa AG. Antibiotics 2021; 10:573.

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Genome-wide proximity between RNA polymerase and DNA topoisomerase I supports transcription in Streptococcus pneumoniae

Ferrándiz M-J, Hernández P, de la Campa AG. PLoS Genet. 2021; 17:e1009542.

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A Small Non-Coding RNA Modulates Expression of Pilus-1 Type in Streptococcus pneumoniae

Acebo P, Herranz C, Bernal-Espenberger L, Gómez-Sanz A, Terron MC, Luque D and Amblar M. Microorganisms. 2021; 9:1883.

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Reactive oxygen species production is a major factor directing the post-antibiotic effect of fluoroquinolones in Streptococcus pneumoniae

García MT, Valenzuela MV, Ferrándiz MJ, de la Campa AG. Antimicrob Agents Chemother. 2019; 63:e00737-19.

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HU of Streptococcus pneumoniae is essential for the preservation of DNA supercoiling

Ferrándiz MJ, Carreño D, Ayora S, de la Campa AG. Front Microbiol. 9:493 (2018).

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Boldine-derived alkaloids inhibit the activity of DNA topoisomerase I and growth of Mycobacterium tuberculosis.

García MT, Carreño D, Tirado-Vélez JM, Ferrándiz MJ, Rodrigues L, Gracia B, Amblar M, Ainsa JA*, de la Campa AG. Front Microbiol. 9:493 (2018).

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Absence of tmRNA has a protective effect against fluoroquinolones in Streptococcus pneumoniae

Brito L, Wilton J, Ferrándiz MJ, Gómez-Sanz A, de la Campa AG, Amblar M. Front. Microbiol. 7:2164 (2017).

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Bridging chromosomal architecture and pathophysiology of Streptococcus pneumoniae

Martín-Galiano AJ, Ferrándiz MJ, de la Campa AG. Genome Biol Evol. 2017; 9:350-361.

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Upregulation of the PatAB transporter confers fluoroquinolone resistance to Streptococcus pseudopneumoniae

Alvarado M, Martín-Galiano AJ, Ferrándiz MJ, Zaballos A, de la Campa AG. Front Microbiol. 8:2074 (2017).

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A novel typing method for Streptococcus pneumoniae using selected surface proteins

Domenech A, Moreno J, Ardanuy C, Liñares J, de la Campa AG, Martin-Galiano AJ. Front Microbiol. 2016; 31;7:420.

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An increase in negative supercoiling in bacteria reveals topology-reacting gene clusters and a homeostatic response mediated by the DNA topoisomerase I gene

Ferrándiz MJ, Martín-Galiano AJ, Arnanz C, Camacho-Soguero I, Tirado-Vélez JM, de la Campa AG. 2016. Nucl Acids Res. 44:7292-7303 (2016).

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Reactive oxygen species contribute to the bactericidal effects of the fluoroquinolone moxifloxacin in Streptococcus pneumoniae

Ferrándiz MJ, Martín-Galiano AJ, Arnanz C, Zimmerman T, de la Campa AG. Antimicrob Agents Chemother. 60:409-417 (2016).

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The fluoroquinolone levofloxacin triggers the transcriptional activation of iron transport genes that contribute to cell death in Streptococcus pneumoniae.

Ferrándiz MJ, de la Campa AG. Antimicrob Agents Chemother. 58:247-257 (2014)

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Fluoroquinolone-resistant pneumococci: dynamics of serotypes and clones in Spain in 2012 compared with those from 2002 and 2006

Domenech A, Tirado-Vélez JM, Fenoll A, Ardanuy C, Yuste J, Liñares J, de la Campa AG. Antimicrob Agents Chemother. 58:2393-2399 (2014).

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The balance between gyrase and topoisomerase I activities determines levels of supercoiling, nucleoid compaction, and viability in bacteria

García-López M, Megias D, Ferrándiz MJ, de la Campa AG. Front Microbiol. 2023; 11;1094692.

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Tyrosine kinase 2 modulates splenic B cells through type I IFN and TLR7 signaling.

Bodega-Mayor I, Delgado-Wicke P, Arrabal A, Alegría-Carrasco E, Nicolao-Gómez A, Jaén-Castaño M, Espadas C, Dopazo A, Martín-Gayo E, Gaspar ML, de Andrés B, Fernández-Ruiz E. Cell Mol Life Sci. 2024 Apr 29;81(1):199.

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