{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"Research Square"}],"indexed":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T05:19:22Z","timestamp":1740719962513,"version":"3.38.0"},"posted":{"date-parts":[[2024,9,25]]},"group-title":"In Review","reference-count":58,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T00:00:00Z","timestamp":1727222400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,9,17]]},"abstract":"<title>Abstract<\/title>\n        <p>In the mammalian host, <italic>Trypanosoma congolense<\/italic> cytoadheres to the vascular endothelium in a process known as sequestration. Although sequestration influences clinical outcome, disease severity and organ pathology, its determinants and mediators remain unknown. Challenges such as the variability of animal models, the only-recently developed tools to genetically manipulate the parasite, and the lack of physiologically relevant <italic>in vitro<\/italic> models have hindered progress. Here, we engineered brain and cardiac 3D bovine endothelial microvessel models that mimic the bovine brain microvasculature and the bovine aorta, respectively. By perfusing these models with two <italic>T. congolense<\/italic> strains, we simulated physiologically relevant conditions and investigated the roles of flow for parasite sequestration and tropism for different endothelial beds. We discovered that sequestration is dependent on cyclic AMP signalling, closely linked to parasite proliferation, but not associated with parasite transmission to the tsetse fly vector. Finally, by comparing the expression profiles of sequestered and non-sequestered parasites collected from a rodent model, we showed gene expression changes in sequestered parasites, including of the surface variant antigens. This work presents a physiologically-relevant platform to study trypanosome interactions with the vasculature and provides a deeper understanding of the molecular and biophysical mechanisms underlying <italic>T. congolense<\/italic> sequestration.<\/p>","DOI":"10.21203\/rs.3.rs-5104603\/v1","type":"posted-content","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T15:39:19Z","timestamp":1727278759000},"source":"Crossref","is-referenced-by-count":0,"title":["Bioengineered 3D microvessels reveal novel determinants of Trypanosoma congolense sequestration"],"prefix":"10.21203","author":[{"given":"Teresa","family":"Porqueddu","sequence":"first","affiliation":[{"name":"Instituto Superior T\u00e9cnico"}]},{"given":"Mariana","family":"De Niz","sequence":"additional","affiliation":[{"name":"Northwestern University"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5237-1223","authenticated-orcid":false,"given":"Aitor","family":"Casas-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Liverpool School of Tropical Medicine"}]},{"given":"Viola","family":"Introini","sequence":"additional","affiliation":[{"name":"EMBL Barcelona"}]},{"given":"Maria","family":"Zorrinho-Almeida","sequence":"additional","affiliation":[{"name":"Universidade Cat\u00f3lica Portuguesa"}]},{"given":"Silvia Sanz","family":"Sender","sequence":"additional","affiliation":[{"name":"EMBL Barcelona"}]},{"given":"Diana","family":"Carrasqueira","sequence":"additional","affiliation":[{"name":"Universidade Cat\u00f3lica Portuguesa"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5752-6586","authenticated-orcid":false,"given":"Luisa","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"Universidade de Lisboa"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7212-6209","authenticated-orcid":false,"given":"Maria","family":"Bernabeu","sequence":"additional","affiliation":[{"name":"EMBL Barcelona"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6590-6626","authenticated-orcid":false,"given":"Sara Silva","family":"Pereira","sequence":"additional","affiliation":[{"name":"Universidade Cat\u00f3lica Portuguesa"}]}],"member":"297","reference":[{"key":"ref1","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.77440","article-title":"Immunopathology and Trypanosoma congolense parasite sequestration cause acute cerebral trypanosomiasis","volume":"11","author":"Silva Pereira S","year":"2022","unstructured":"Silva Pereira S et al (2022) Immunopathology and Trypanosoma congolense parasite sequestration cause acute cerebral trypanosomiasis. Elife 11","journal-title":"Elife"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.3389\/fimmu.2018.02016","article-title":"Cerebral Malaria in Mouse and Man","volume":"9","author":"Ghazanfari N","year":"2018","unstructured":"Ghazanfari N, Mueller SN, Heath WR (2018) Cerebral Malaria in Mouse and Man. Front Immunol 9:2016","journal-title":"Front Immunol"},{"key":"ref3","first-page":"1","article-title":"Interplay between attenuation-and virulence-factors of Babesia Bovis and their contribution to the establishment of persistent infections in cattle","volume":"8","author":"Gallego-Lopez GM","year":"2019","unstructured":"Gallego-Lopez GM, Cooke BM, Suarez CE (2019) Interplay between attenuation-and virulence-factors of Babesia Bovis and their contribution to the establishment of persistent infections in cattle. Pathogens 8:1\u201313","journal-title":"Pathogens"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"e1011889","DOI":"10.1371\/journal.ppat.1011889","article-title":"A conserved trypanosomatid differentiation regulator controls substrate attachment and morphological development in Trypanosoma congolense","volume":"20","author":"Silvester E","year":"2024","unstructured":"Silvester E et al (2024) A conserved trypanosomatid differentiation regulator controls substrate attachment and morphological development in Trypanosoma congolense. PLoS Pathog 20:e1011889","journal-title":"PLoS Pathog"},{"year":"2019","author":"Bernabeu M","key":"ref5","unstructured":"Bernabeu M et al (2019) Binding Heterogeneity of Plasmodium falciparum to Engineered 3D Brain Microvessels Is Mediated by EPCR and ICAM-1. mBio 10, e00420-19"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"233","DOI":"10.3109\/10739689709146787","article-title":"Blood flow in the cerebral capillary network: A review emphasizing observations with intravital microscopy","volume":"4","author":"Hudetz AG","year":"1997","unstructured":"Hudetz AG (1997) Blood flow in the cerebral capillary network: A review emphasizing observations with intravital microscopy. Microcirculation 4:233\u2013252","journal-title":"Microcirculation"},{"year":"2005","author":"Lipowsky HH","key":"ref7","unstructured":"Lipowsky HH (2005) Microvascular rheology and hemodynamics. Microcirculation vol. 12 5\u201315 10739680590894966"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1038\/jcbfm.2012.5","article-title":"Control of brain capillary blood flow","volume":"32","author":"Itoh Y","year":"2012","unstructured":"Itoh Y, Suzuki N (2012) Control of brain capillary blood flow. J Cereb Blood Flow Metab 32:1167\u20131176","journal-title":"J Cereb Blood Flow Metab"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00931503","article-title":"Flagellum-mediated adhesion of Trypanosoma congolense to bovine aorta endothelial cells","volume":"81","author":"Hemphill A","year":"1995","unstructured":"Hemphill A, Ross CA (1995) Flagellum-mediated adhesion of Trypanosoma congolense to bovine aorta endothelial cells. Parasitol Res 81:412\u2013420","journal-title":"Parasitol Res"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"E1772","DOI":"10.1073\/pnas.1120461109","article-title":"A subset of group A-like var genes encodes the malaria parasite ligands for binding to human brain endothelial cells","volume":"109","author":"Claessens A","year":"2012","unstructured":"Claessens A et al (2012) A subset of group A-like var genes encodes the malaria parasite ligands for binding to human brain endothelial cells. Proc Natl Acad Sci U S A 109:E1772","journal-title":"Proc Natl Acad Sci U S A"},{"year":"2016","author":"Avril M","key":"ref11","unstructured":"Avril M, Bernabeu M, Benjamin M, Brazier AJ, Smith JD (2016) Interaction between Endothelial Protein C Receptor and Intercellular Adhesion Molecule 1 to Mediate Binding of Plasmodium falciparum -Infected Erythrocytes to Endothelial Cells. mBio 7"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1016\/j.bmc.2016.02.032","article-title":"Synthesis and evaluation of analogs of the phenylpyridazinone NPD-001 as potent trypanosomal TbrPDEB1 phosphodiesterase inhibitors and in vitro trypanocidals","volume":"24","author":"Veerman J","year":"2016","unstructured":"Veerman J et al (2016) Synthesis and evaluation of analogs of the phenylpyridazinone NPD-001 as potent trypanosomal TbrPDEB1 phosphodiesterase inhibitors and in vitro trypanocidals. Bioorg Med Chem 24:1573\u20131581","journal-title":"Bioorg Med Chem"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1093\/jac\/dkz516","article-title":"Evaluation of phthalazinone phosphodiesterase inhibitors with improved activity and selectivity against Trypanosoma cruzi","volume":"75","author":"Ara\u00fajo JS","year":"2020","unstructured":"De Ara\u00fajo JS et al (2020) Evaluation of phthalazinone phosphodiesterase inhibitors with improved activity and selectivity against Trypanosoma cruzi. J Antimicrob Chemother 75:958\u2013967","journal-title":"J Antimicrob Chemother"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"e2306848120","DOI":"10.1073\/pnas.2306848120","article-title":"The developmental hierarchy and scarcity of replicative slender trypanosomes in blood challenges their role in infection maintenance","volume":"120","author":"Larcombe SD","year":"2023","unstructured":"Larcombe SD, Briggs EM, Savill N, Szoor B, Matthews K (2023) The developmental hierarchy and scarcity of replicative slender trypanosomes in blood challenges their role in infection maintenance. Proc Natl Acad Sci U S A 120:e2306848120","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref15","first-page":"1","volume":"6","author":"Oberholzer M","year":"2015","unstructured":"Oberholzer M, Saada EA, Hill KL, Cyclic (2015) AMP Regulates Social Behav Afr Trypanosomes mBio 6:1\u201311","journal-title":"AMP Regulates Social Behav Afr Trypanosomes mBio"},{"key":"ref16","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-022-28293-w","article-title":"Cyclic AMP signalling and glucose metabolism mediate pH taxis by African trypanosomes","volume":"13","author":"Shaw S","year":"2022","unstructured":"Shaw S et al (2022) Cyclic AMP signalling and glucose metabolism mediate pH taxis by African trypanosomes. Nat Commun 13","journal-title":"Nat Commun"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1080\/00034983.1983.11811740","article-title":"Enzyme polymorphism and the distribution of Trypanosoma congolense isolates","volume":"77","author":"Young CJ","year":"1983","unstructured":"Young CJ, Godfrey DG (1983) Enzyme polymorphism and the distribution of Trypanosoma congolense isolates. Ann Trop Med Parasitol 77:467\u2013481","journal-title":"Ann Trop Med Parasitol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.jmoldx.2014.02.006","article-title":"Diagnosis of trypanosomatid infections: Targeting the spliced leader RNA","volume":"16","author":"Gonz\u00e1lez-Andrade P","year":"2014","unstructured":"Gonz\u00e1lez-Andrade P et al (2014) Diagnosis of trypanosomatid infections: Targeting the spliced leader RNA. J Mol Diagn 16:400\u2013404","journal-title":"J Mol Diagn"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1038\/s41467-020-14575-8","article-title":"Variant antigen diversity in Trypanosoma vivax is not driven by recombination","volume":"11","author":"Silva Pereira S","year":"2020","unstructured":"Silva Pereira S et al (2020) Variant antigen diversity in Trypanosoma vivax is not driven by recombination. Nat Commun 11:844","journal-title":"Nat Commun"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"3725","DOI":"10.1038\/s41598-017-03987-0","article-title":"Multiplexed Spliced-Leader Sequencing: A high-throughput, selective method for RNA-seq in Trypanosomatids","volume":"7","author":"Cuypers B","year":"2017","unstructured":"Cuypers B et al (2017) Multiplexed Spliced-Leader Sequencing: A high-throughput, selective method for RNA-seq in Trypanosomatids. Sci Rep 7:3725","journal-title":"Sci Rep"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"2458","DOI":"10.1093\/gbe\/evy186","article-title":"The structure of a conserved telomeric region associated with variant antigen loci in the blood parasite Trypanosoma congolense","volume":"10","author":"Abbas AH","year":"2018","unstructured":"Abbas AH et al (2018) The structure of a conserved telomeric region associated with variant antigen loci in the blood parasite Trypanosoma congolense. Genome Biol Evol 10:2458\u20132473","journal-title":"Genome Biol Evol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"e0006863","DOI":"10.1371\/journal.pntd.0006863","article-title":"R. A gene expression comparison of Trypanosoma brucei and Trypanosoma congolense in the bloodstream of the mammalian host reveals species-specific adaptations to density-dependent development","volume":"12","author":"Silvester E","year":"2018","unstructured":"Silvester E, Ivens A, Matthews K (2018) R. A gene expression comparison of Trypanosoma brucei and Trypanosoma congolense in the bloodstream of the mammalian host reveals species-specific adaptations to density-dependent development. PLoS Negl Trop Dis 12:e0006863","journal-title":"PLoS Negl Trop Dis"},{"year":"2019","author":"Silva Pereira S","key":"ref23","unstructured":"Silva Pereira S, Heap J, Jones AR, Jackson AP (2019) VAPPER: High-throughput variant antigen profiling in African trypanosomes of livestock. Gigascience 8, 1\u20138"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1101\/gr.234146.118","article-title":"Variant antigen repertoires in Trypanosoma congolense populations and experimental infections can be profiled from deep sequence data with a set of universal protein motifs","volume":"28","author":"Silva Pereira S","year":"2018","unstructured":"Silva Pereira S et al (2018) Variant antigen repertoires in Trypanosoma congolense populations and experimental infections can be profiled from deep sequence data with a set of universal protein motifs. Genome Res 28:1383\u20131394","journal-title":"Genome Res"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1101\/2024.01.25.577124","author":"Reyes RA","year":"2024","unstructured":"Reyes RA et al (2024) Broadly inhibitory antibodies against severe malaria virulence proteins. bioRxiv 10.1101\/2024.01.25.577124"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiae315","article-title":"Plasma From Older Children in Malawi Inhibits Plasmodium falciparum Binding in 3-Dimensional Brain Microvessels","author":"Joof F","year":"2024","unstructured":"Joof F et al (2024) Plasma From Older Children in Malawi Inhibits Plasmodium falciparum Binding in 3-Dimensional Brain Microvessels. J Infect Dis. 10.1093\/infdis\/jiae315","journal-title":"J Infect Dis"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"113253","DOI":"10.1016\/j.celrep.2023.113253","article-title":"Probing cerebral malaria inflammation in 3D human brain microvessels","volume":"42","author":"Howard C","year":"2023","unstructured":"Howard C, Joof F, Hu R, Smith JD, Zheng Y (2023) Probing cerebral malaria inflammation in 3D human brain microvessels. Cell Rep 42:113253","journal-title":"Cell Rep"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1101\/2024.03.29.587334","author":"Rory KM","year":"2024","unstructured":"Rory KM, Long et al (2024) Plasmodium falciparum disruption of pericyte angiopoietin-1 secretion contributes to barrier breakdown in a 3D brain microvessel model. biorxiv 10.1101\/2024.03.29.587334"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"e0006690","DOI":"10.1371\/journal.pntd.0006690","article-title":"Trypanosoma brucei triggers a marked immune response in male reproductive organs","volume":"12","author":"Carvalho T","year":"2018","unstructured":"Carvalho T et al (2018) Trypanosoma brucei triggers a marked immune response in male reproductive organs. PLoS Negl Trop Dis 12:e0006690","journal-title":"PLoS Negl Trop Dis"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/j.chom.2016.05.002","article-title":"Trypanosoma brucei Parasites Occupy and Functionally Adapt to the Adipose Tissue in Mice","volume":"19","author":"Trindade S","year":"2016","unstructured":"Trindade S et al (2016) Trypanosoma brucei Parasites Occupy and Functionally Adapt to the Adipose Tissue in Mice. Cell Host Microbe 19:837\u2013848","journal-title":"Cell Host Microbe"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7554\/eLife.17716","article-title":"The skin is a significant but overlooked anatomical reservoir for vector-borne African trypanosomes","volume":"5","author":"Capewell P","year":"2016","unstructured":"Capewell P et al (2016) The skin is a significant but overlooked anatomical reservoir for vector-borne African trypanosomes. Elife 5:1\u201317","journal-title":"Elife"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"e1005744","DOI":"10.1371\/journal.ppat.1005744","article-title":"The Dermis as a Delivery Site of Trypanosoma brucei for Tsetse Flies","volume":"12","author":"Caljon G","year":"2016","unstructured":"Caljon G et al (2016) The Dermis as a Delivery Site of Trypanosoma brucei for Tsetse Flies. PLoS Pathog 12:e1005744","journal-title":"PLoS Pathog"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"109741","DOI":"10.1016\/j.celrep.2021.109741","article-title":"Organotypic endothelial adhesion molecules are key for Trypanosoma brucei tropism and virulence","volume":"36","author":"Niz M","year":"2021","unstructured":"De Niz M et al (2021) Organotypic endothelial adhesion molecules are key for Trypanosoma brucei tropism and virulence. Cell Rep 36:109741","journal-title":"Cell Rep"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1017\/S0031182000076514","article-title":"The interaction of Trypanosoma congolense with endothelial cells","volume":"109","author":"Hemphill A","year":"1994","unstructured":"Hemphill A, Frame I, Ross CA (1994) The interaction of Trypanosoma congolense with endothelial cells. Parasitology 109:631\u2013641","journal-title":"Parasitology"},{"key":"ref35","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-019-08696-y","article-title":"Flagellar cAMP signaling controls trypanosome progression through host tissues","volume":"10","author":"Shaw S","year":"2019","unstructured":"Shaw S et al (2019) Flagellar cAMP signaling controls trypanosome progression through host tissues. Nat Commun 10","journal-title":"Nat Commun"},{"key":"ref36","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.66028","article-title":"Unexpected plasticity in the life cycle of trypanosoma brucei","volume":"10","author":"Schuster S","year":"2021","unstructured":"Schuster S et al (2021) Unexpected plasticity in the life cycle of trypanosoma brucei. Elife 10","journal-title":"Elife"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.cellsig.2010.08.015","article-title":"Down-regulation of cyclic nucleotide phosphodiesterase PDE1A is the key event of p73 and UHRF1 deregulation in thymoquinone-induced acute lymphoblastic leukemia cell apoptosis","volume":"23","author":"Abusnina A","year":"2011","unstructured":"Abusnina A et al (2011) Down-regulation of cyclic nucleotide phosphodiesterase PDE1A is the key event of p73 and UHRF1 deregulation in thymoquinone-induced acute lymphoblastic leukemia cell apoptosis. Cell Signal 23:152\u2013160","journal-title":"Cell Signal"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1016\/j.cellsig.2014.03.031","article-title":"Role of phosphodiesterase 2 in growth and invasion of human malignant melanoma cells","volume":"26","author":"Hiramoto K","year":"2014","unstructured":"Hiramoto K et al (2014) Role of phosphodiesterase 2 in growth and invasion of human malignant melanoma cells. Cell Signal 26:1807\u20131817","journal-title":"Cell Signal"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jns.2012.06.005","article-title":"Phosphodiesterase inhibitor modulation of brain microvascular endothelial cell barrier properties","volume":"320","author":"Liu S","year":"2012","unstructured":"Liu S, Yu C, Yang F, Paganini-Hill A, Fisher MJ (2012) Phosphodiesterase inhibitor modulation of brain microvascular endothelial cell barrier properties. J Neurol Sci 320:45\u201351","journal-title":"J Neurol Sci"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1172\/JCI116346","article-title":"Role of phosphodiesterases in the regulation of endothelial permeability in vitro","volume":"91","author":"Suttorp N","year":"1993","unstructured":"Suttorp N, Weber U, Welsch T, Schudt C (1993) Role of phosphodiesterases in the regulation of endothelial permeability in vitro. J Clin Invest 91:1421\u20131428","journal-title":"J Clin Invest"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"5793","DOI":"10.1096\/fj.201700818RRR","article-title":"Prolonged activation of cAMP signaling leads to endothelial barrier disruption via transcriptional repression of RRAS","volume":"32","author":"Perrot CY","year":"2018","unstructured":"Perrot CY, Sawada J, Komatsu M (2018) Prolonged activation of cAMP signaling leads to endothelial barrier disruption via transcriptional repression of RRAS. FASEB J 32:5793\u20135812","journal-title":"FASEB J"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"A1165","DOI":"10.1096\/fasebj.21.6.A1165-c","article-title":"Differential Regulation of Endothelial Cell Permeability by cGMP via Phosphodiesterases 2 and 3","volume":"21","author":"Surapisitchat J","year":"2007","unstructured":"Surapisitchat J, Jeon K-I, Yan C, Beavo JA (2007) Differential Regulation of Endothelial Cell Permeability by cGMP via Phosphodiesterases 2 and 3. FASEB J 21:A1165\u2013A1165","journal-title":"FASEB J"},{"year":"2022","author":"Denecke S","key":"ref43","unstructured":"Denecke S et al (2022) Adhesion of Crithidia fasciculata promotes a rapid change in developmental fate driven by cAMP signaling"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1080\/00034983.1983.11811740","article-title":"Enzyme polymorphism and the distribution of Trypanosoma congolense isolates","volume":"77","author":"Young CJ","year":"1983","unstructured":"Young CJ, Godfrey DG (1983) Enzyme polymorphism and the distribution of Trypanosoma congolense isolates. Ann Trop Med Parasitol 77:467\u2013481","journal-title":"Ann Trop Med Parasitol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/nature12216","article-title":"Severe malaria is associated with parasite binding to endothelial protein C receptor","volume":"498","author":"Turner L","year":"2013","unstructured":"Turner L et al (2013) Severe malaria is associated with parasite binding to endothelial protein C receptor. Nature 498:502\u2013505","journal-title":"Nature"},{"year":"2019","author":"Niz M","key":"ref46","unstructured":"De Niz M, Nacer A, Frischknecht F (2019) Intravital microscopy: Imaging host-parasite interactions in the brain. Cell Microbiol e13024 (2019)"},{"year":"2020","author":"Niz M","key":"ref47","unstructured":"De Niz M, Carvalho T, Carlos Penha-Gon\u00e7alves, Agop-Nersesian C (2020) Intravital imaging of host-parasite interactions in organs of the thoracic and abdominopelvic cavities. Cell Microbiol 22, e13201"},{"key":"ref48","first-page":"13023","article-title":"Intravital imaging of host-parasite interactions in skin and adipose tissues","volume":"21","author":"Niz M","year":"2019","unstructured":"De Niz M et al (2019) Intravital imaging of host-parasite interactions in skin and adipose tissues. Cell Microbiol 21:13023","journal-title":"Cell Microbiol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1017\/S0031182000080021","article-title":"An artificial feeding technique for Glossina","volume":"63","author":"Moloo SK","year":"1971","unstructured":"Moloo SK (1971) An artificial feeding technique for Glossina. Parasitology 63:507\u2013512","journal-title":"Parasitology"},{"key":"ref50","first-page":"15","article-title":"Ultrafast universal RNA-seq aligner","volume":"STAR","author":"Dobin A","year":"2013","unstructured":"Dobin A et al (2013) Ultrafast universal RNA-seq aligner. Bioinf 29 STAR:15\u201321","journal-title":"Bioinf 29"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"Li H","year":"2009","unstructured":"Li H et al (2009) The Sequence Alignment\/Map format and SAMtools. Bioinformatics 25:2078\u20132079","journal-title":"Bioinformatics"},{"key":"ref52","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3122","article-title":"StringTie enables improved reconstruction of a transcriptome from RNA-seq reads","author":"Pertea M","year":"2015","unstructured":"Pertea M et al (2015) StringTie enables improved reconstruction of a transcriptome from RNA-seq reads. Nat Biotechnol. 10.1038\/nbt.3122","journal-title":"Nat Biotechnol"},{"key":"ref53","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: a Bioconductor package for differential expression analysis of digital gene expression data","author":"Robinson MD","year":"2010","unstructured":"Robinson MD, McCarthy DJ, Smyth GK (2010) edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 10.1093\/bioinformatics\/btp616","journal-title":"Bioinformatics"},{"key":"ref54","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2014-15-2-r29","article-title":"Precision weights unlock linear model analysis tools for RNA-seq read counts","author":"Law CW","year":"2014","unstructured":"Law CW, Chen Y, Shi W, Smyth GK, Voom (2014) Precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol. 10.1186\/gb-2014-15-2-r29","journal-title":"Genome Biol"},{"year":"2019","author":"Silva Pereira S","key":"ref55","unstructured":"Silva Pereira S, Heap J, Jones AR, Jackson AP (2019) VAPPER: High-throughput variant antigen profiling in African trypanosomes of livestock. Gigascience 8, 1\u20138"},{"year":"2005","author":"Subramanian A","key":"ref56","unstructured":"Subramanian A et al (2005) Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proceedings of the National Academy of Sciences 102, 15545\u201315550"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"W130","DOI":"10.1093\/nar\/gkx356","article-title":"WebGestalt 2017: a more comprehensive, powerful, flexible and interactive gene set enrichment analysis toolkit","volume":"45","author":"Wang J","year":"2017","unstructured":"Wang J, Vasaikar S, Shi Z, Greer M, Zhang B (2017) WebGestalt 2017: a more comprehensive, powerful, flexible and interactive gene set enrichment analysis toolkit. Nucleic Acids Res 45:W130\u2013W137","journal-title":"Nucleic Acids Res"},{"year":"2018","author":"Jain C","key":"ref58","unstructured":"Jain C, Koren S, Dilthey A, Phillippy AM, Aluru S (2018) A fast adaptive algorithm for computing whole-genome homology maps. in Bioinformatics vol. 34 i748\u2013i756Oxford University Press"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/www.researchsquare.com\/article\/rs-5104603\/v1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.researchsquare.com\/article\/rs-5104603\/v1.html","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T08:09:41Z","timestamp":1740643781000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.researchsquare.com\/article\/rs-5104603\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,25]]},"references-count":58,"URL":"https:\/\/doi.org\/10.21203\/rs.3.rs-5104603\/v1","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1038\/s42003-025-07739-z","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2024,9,25]]},"subtype":"preprint"}}