Pub Date : 2024-08-07DOI: 10.1101/2024.08.01.606266
Caris A. Wadding-Lee, Megan Jay, Shannon M. Jones, Joel Thompson, Deborah A. Howatt, Alan Daugherty, Nigel Mackman, A. Phillip Owens
Objective Cardiovascular disease (CVD) is a significant burden globally and, despite current therapeutics, remains the leading cause of death. Platelet inhibitors are of interest in CVD treatment to reduce thrombus formation post-plaque rupture as well their contribution to inflammation throughout the progression of atherosclerosis. Protease activated receptor 4 (PAR4) is a receptor highly expressed by platelets, strongly activated by thrombin, and plays a vital role in platelet activation and aggregation. However, the role of PAR4
{"title":"Attenuation of Atherosclerosis with PAR4 Deficiency: Differential Platelet Outcomes in apoE-/- vs. Ldlr-/- Mice","authors":"Caris A. Wadding-Lee, Megan Jay, Shannon M. Jones, Joel Thompson, Deborah A. Howatt, Alan Daugherty, Nigel Mackman, A. Phillip Owens","doi":"10.1101/2024.08.01.606266","DOIUrl":"https://doi.org/10.1101/2024.08.01.606266","url":null,"abstract":"<strong>Objective</strong> Cardiovascular disease (CVD) is a significant burden globally and, despite current therapeutics, remains the leading cause of death. Platelet inhibitors are of interest in CVD treatment to reduce thrombus formation post-plaque rupture as well their contribution to inflammation throughout the progression of atherosclerosis. Protease activated receptor 4 (PAR4) is a receptor highly expressed by platelets, strongly activated by thrombin, and plays a vital role in platelet activation and aggregation. However, the role of PAR4","PeriodicalId":501471,"journal":{"name":"bioRxiv - Pathology","volume":"198 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141944805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The liver has a strong regenerative capacity, but the mechanisms of liver regeneration are not well understood. Furthermore, many previous studies on liver regeneration have been conducted in partial hepatectomy models, which may differ from acute liver injury with inflammation and necrosis, as observed in many clinical cases. In this study, we conducted a single-cell RNA-seq analysis (scRNA-seq) of liver regeneration in mice treated with acetaminophen (APAP) using publicly available data. We discovered that two cell proliferation populations appeared simultaneously during a single regenerative process. The two populations differed significantly in terms of differentiation, localization, proliferation rate, and signal response. Furthermore, one of the populations was induced by contact with necrotic tissue and exhibited a higher proliferative capacity with a dedifferentiated feature. These findings can shed new light on liver regeneration and aid in the development of therapeutic strategies for liver failure.
{"title":"Two types of regeneration mechanism in acute liver injury","authors":"Tomomi Aoyagi, Takeshi Goya, Koji Imoto, Yuki Azuma, Tomonobu Hioki, Motoyuki Kohjima, Masatake Tanaka, Yoshinao Oda, Yoshihiro Ogawa","doi":"10.1101/2024.08.04.606468","DOIUrl":"https://doi.org/10.1101/2024.08.04.606468","url":null,"abstract":"The liver has a strong regenerative capacity, but the mechanisms of liver regeneration are not well understood. Furthermore, many previous studies on liver regeneration have been conducted in partial hepatectomy models, which may differ from acute liver injury with inflammation and necrosis, as observed in many clinical cases. In this study, we conducted a single-cell RNA-seq analysis (scRNA-seq) of liver regeneration in mice treated with acetaminophen (APAP) using publicly available data. We discovered that two cell proliferation populations appeared simultaneously during a single regenerative process. The two populations differed significantly in terms of differentiation, localization, proliferation rate, and signal response. Furthermore, one of the populations was induced by contact with necrotic tissue and exhibited a higher proliferative capacity with a dedifferentiated feature. These findings can shed new light on liver regeneration and aid in the development of therapeutic strategies for liver failure.","PeriodicalId":501471,"journal":{"name":"bioRxiv - Pathology","volume":"122 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141944806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-31DOI: 10.1101/2024.07.31.605973
A. Marin-Moreno, F. Reine, F. Jaffrézic, L. Herzog, H. Rezaei, I. Quadrio, S. Haïk, V. Béringue, D. Martin
Prion diseases are fatal neurodegenerative diseases that affect mammals through the transconformation of a host protein, the prion protein (PrP), into a toxic and pathogenic conformer termed PrPSc. Until now, the diagnosis is only confirmed with a post-mortem histology study of the central nervous system. Among the methods to detect the etiological agent, in vitro amplification techniques have emerged as very sensitive, highly specific and rapid tools, even though some prion strains remain refractory or difficult to amplify. Here we report the use of a new recombinant substrate for Real-Time Quaking Induced Conversion (RT-QuIC), a natural polymorphism of human prion protein with a lysine at position 219 instead of a glutamic acid, PrP E219K. This substrate amplifies the six sporadic human strains responsible for Creutzfeldt-Jakob Disease (CJD) and the strain responsible for its variant form in a few hours and over a large dilution range of the seeds. Moreover, based on the lag time of the amplification reactions, the PrP E219K substrate allows to discriminate between sporadic and variant CJD strains, a first step towards an ante-mortem typing of the prion strain affecting a patient.
{"title":"Human PrP E219K as a new and promising substrate for RT-QuIC amplification of human prion strains: a first step towards strain discrimination","authors":"A. Marin-Moreno, F. Reine, F. Jaffrézic, L. Herzog, H. Rezaei, I. Quadrio, S. Haïk, V. Béringue, D. Martin","doi":"10.1101/2024.07.31.605973","DOIUrl":"https://doi.org/10.1101/2024.07.31.605973","url":null,"abstract":"Prion diseases are fatal neurodegenerative diseases that affect mammals through the transconformation of a host protein, the prion protein (PrP), into a toxic and pathogenic conformer termed PrP<sup>Sc</sup>. Until now, the diagnosis is only confirmed with a post-mortem histology study of the central nervous system. Among the methods to detect the etiological agent, <em>in vitro</em> amplification techniques have emerged as very sensitive, highly specific and rapid tools, even though some prion strains remain refractory or difficult to amplify. Here we report the use of a new recombinant substrate for Real-Time Quaking Induced Conversion (RT-QuIC), a natural polymorphism of human prion protein with a lysine at position 219 instead of a glutamic acid, PrP E219K. This substrate amplifies the six sporadic human strains responsible for Creutzfeldt-Jakob Disease (CJD) and the strain responsible for its variant form in a few hours and over a large dilution range of the seeds. Moreover, based on the lag time of the amplification reactions, the PrP E219K substrate allows to discriminate between sporadic and variant CJD strains, a first step towards an ante-mortem typing of the prion strain affecting a patient.","PeriodicalId":501471,"journal":{"name":"bioRxiv - Pathology","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141882033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-31DOI: 10.1101/2024.07.30.605216
Ting Zhou, Huan Yang, Carmel Assa, Elise DeRoo, Jack Bontekoe, Brian Burkel, Suzanne M Ponik, Hong S. Lu, Alan Daugherty, Bo Liu
Rationale: Rupture of abdominal aortic aneurysms (AAA) is associated with high mortality. However, the precise molecular and cellular drivers of AAA rupture remain elusive. Our prior study showed that global and myeloid-specific deletion of matricellular protein thrombospondin-1 (TSP1) protects mice from aneurysm formation primarily by inhibiting vascular inflammation. Objective: To investigate the cellular and molecular mechanisms that drive AAA rupture by testing how TSP1 deficiency in different cell populations affects the rupture event. Methods and Results: We deleted TSP1 in endothelial cells and macrophages --- the major TSP1-expressing cells in aneurysmal tissues ---- by crossbreeding Thbs1 flox/flox mice with VE-cadherin Cre and Lyz2-cre mice, respectively. Aortic aneurysm and rupture were induced by angiotensin II in mice with hypercholesterolemia. Myeloid-specific Thbs1 knockout, but not endothelial-specific knockout, increased the rate of lethal aortic rupture by more than 2 folds. Combined analyses of single-cell RNA sequencing and histology showed a unique cellular and molecular signature of the rupture-prone aorta that was characterized by a broad suppression in inflammation and extracellular matrix production. Visium spatial transcriptomic analysis on human AAA tissues showed a correlation between low TSP1 expression and aortic dissection. Conclusions: TSP1 expression by myeloid cells negatively regulates aneurysm rupture, likely through promoting the matrix repair phenotypes of vascular smooth muscle cells thereby increasing the strength of the vascular wall.
{"title":"Myeloid-Specific Thrombospondin-1 Deficiency Exacerbates Aortic Rupture via Broad Suppression of Extracellular Matrix Proteins","authors":"Ting Zhou, Huan Yang, Carmel Assa, Elise DeRoo, Jack Bontekoe, Brian Burkel, Suzanne M Ponik, Hong S. Lu, Alan Daugherty, Bo Liu","doi":"10.1101/2024.07.30.605216","DOIUrl":"https://doi.org/10.1101/2024.07.30.605216","url":null,"abstract":"Rationale: Rupture of abdominal aortic aneurysms (AAA) is associated with high mortality. However, the precise molecular and cellular drivers of AAA rupture remain elusive. Our prior study showed that global and myeloid-specific deletion of matricellular protein thrombospondin-1 (TSP1) protects mice from aneurysm formation primarily by inhibiting vascular inflammation. Objective: To investigate the cellular and molecular mechanisms that drive AAA rupture by testing how TSP1 deficiency in different cell populations affects the rupture event. Methods and Results: We deleted TSP1 in endothelial cells and macrophages --- the major TSP1-expressing cells in aneurysmal tissues ---- by crossbreeding Thbs1 flox/flox mice with VE-cadherin Cre and Lyz2-cre mice, respectively. Aortic aneurysm and rupture were induced by angiotensin II in mice with hypercholesterolemia. Myeloid-specific Thbs1 knockout, but not endothelial-specific knockout, increased the rate of lethal aortic rupture by more than 2 folds. Combined analyses of single-cell RNA sequencing and histology showed a unique cellular and molecular signature of the rupture-prone aorta that was characterized by a broad suppression in inflammation and extracellular matrix production. Visium spatial transcriptomic analysis on human AAA tissues showed a correlation between low TSP1 expression and aortic dissection.\u0000Conclusions: TSP1 expression by myeloid cells negatively regulates aneurysm rupture, likely through promoting the matrix repair phenotypes of vascular smooth muscle cells thereby increasing the strength of the vascular wall.","PeriodicalId":501471,"journal":{"name":"bioRxiv - Pathology","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141871264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-31DOI: 10.1101/2024.07.30.605894
Daniel Nobach, Leif Raeder, Jana Mueller, Sibylle Herzog, Markus Eickmann, Christiane Herden
Numbers of human encephalitis cases caused by infection with Borna disease virus 1 (BoDV1) increase continuously in endemic areas. The reservoir host of BoDV1 is the bicoloured white-toothed shrew, albeit few naturally infected individuals of other shrew species have been detected. To establish a reliable experimental reservoir model, 15 greater white-toothed shrews were infected with a shrew-derived BoDV1 isolate by different inoculation routes (intracerebral, intranasal, oral, subcutaneous, intraperitoneal) and monitored up to 41 days. Except for the oral route all other animals (12/15) were successfully infected, and the majority of them displayed temporary reduced feed intake and loss of body weight but no inflammatory lesions. Infectious virus was isolated from 11/12 infected animals. Viral RNA was demonstrated by RT-qPCR in the central nervous system (CNS) and the majority of organs. Immunohistochemistry demonstrated BoDV1 antigen in neurons and astrocytes in the CNS and peripheral nerves. High viral loads in the CNS and the spinal cord points towards spread from periphery to the CNS to enhance viral replication, and subsequent centrifugal spread to organs capable of secretion and excretions. In general, successful experimental BoDV1 infection of shrews proves their usefulness as animal model, enabling further studies on maintenance, transmission, pathogenesis, and risk assessment for human spill-over infections.
{"title":"Experimental Infection of greater white-toothed Shrews (Crocidura russula) with Borna disease virus 1: Insights into Viral Spread and Shedding","authors":"Daniel Nobach, Leif Raeder, Jana Mueller, Sibylle Herzog, Markus Eickmann, Christiane Herden","doi":"10.1101/2024.07.30.605894","DOIUrl":"https://doi.org/10.1101/2024.07.30.605894","url":null,"abstract":"Numbers of human encephalitis cases caused by infection with Borna disease virus 1 (BoDV1) increase continuously in endemic areas. The reservoir host of BoDV1 is the bicoloured white-toothed shrew, albeit few naturally infected individuals of other shrew species have been detected. To establish a reliable experimental reservoir model, 15 greater white-toothed shrews were infected with a shrew-derived BoDV1 isolate by different inoculation routes (intracerebral, intranasal, oral, subcutaneous, intraperitoneal) and monitored up to 41 days. Except for the oral route all other animals (12/15) were successfully infected, and the majority of them displayed temporary reduced feed intake and loss of body weight but no inflammatory lesions. Infectious virus was isolated from 11/12 infected animals. Viral RNA was demonstrated by RT-qPCR in the central nervous system (CNS) and the majority of organs. Immunohistochemistry demonstrated BoDV1 antigen in neurons and astrocytes in the CNS and peripheral nerves. High viral loads in the CNS and the spinal cord points towards spread from periphery to the CNS to enhance viral replication, and subsequent centrifugal spread to organs capable of secretion and excretions. In general, successful experimental BoDV1 infection of shrews proves their usefulness as animal model, enabling further studies on maintenance, transmission, pathogenesis, and risk assessment for human spill-over infections.","PeriodicalId":501471,"journal":{"name":"bioRxiv - Pathology","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141871337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-29DOI: 10.1101/2024.07.28.604919
Ziyang Li, Marij J.P Welters, Aiko P.J de Vries, Jan Anthonie Bruijn, Hans J Baelde, Jesper Kers
Background: Rapid diagnosis is pivotal in kidney disease for timely and targeted treatment. Conventional microscopic and molecular assessments from biopsy tissues rely on extra sample processing (e.g., formalin-fixation, paraffin-embedding (FFPE)) or an extra biopsy core (e.g., Molecular Microscope Diagnostic System [MMDx]), making same-day diagnosis impractical. Therefore, we introduce a novel and freely accessible material, the biopsy transport medium (BTM), which can serve as a source of biomarkers with high potential and is promising for accelerating the assessment workflow. Methods: Biopsies were cut from tumor-free tissues obtained from nephrectomies to create BTM mimics for homogenization. We optimized the RNA extraction procedure from BTM by investigating crucial steps in the process. We measured the quantity and integrity of the RNA and different biomarkers derived from BTM through qPCR. Additionally, we performed the Banff Human Organ Transplant (B-HOT) panel on BTM from clinical biopsies using the NanoString nCounter platform as a proof-of-concept study. Results: Our results showed that the storage times ranging from 0.5 hours to 24 hours did not significantly affect RNA quality and yield. Differential gene expression analysis on allograft rejection BTM described specific profiles related to rejection. A significant correlation was observed between rejection-related transcripts and the corresponding Banff lesion scores. Conclusion: This study validated that the BTM can provide transcriptomic information relevant to the state of the kidney. The proof-of-concept study demonstrated that BTM has great potential for reflecting the status of the transplanted kidney. Tailored qPCR panels could allow for fast (same-day) molecular diagnosis.
{"title":"Rapid liquid biopsy assessment through gene profiling from the kidney biopsy transport medium: a technical validation and a proof-of-concept pilot study","authors":"Ziyang Li, Marij J.P Welters, Aiko P.J de Vries, Jan Anthonie Bruijn, Hans J Baelde, Jesper Kers","doi":"10.1101/2024.07.28.604919","DOIUrl":"https://doi.org/10.1101/2024.07.28.604919","url":null,"abstract":"Background: Rapid diagnosis is pivotal in kidney disease for timely and targeted treatment. Conventional microscopic and molecular assessments from biopsy tissues rely on extra sample processing (e.g., formalin-fixation, paraffin-embedding (FFPE)) or an extra biopsy core (e.g., Molecular Microscope Diagnostic System [MMDx]), making same-day diagnosis impractical. Therefore, we introduce a novel and freely accessible material, the biopsy transport medium (BTM), which can serve as a source of biomarkers with high potential and is promising for accelerating the assessment workflow. Methods: Biopsies were cut from tumor-free tissues obtained from nephrectomies to create BTM mimics for homogenization. We optimized the RNA extraction procedure from BTM by investigating crucial steps in the process. We measured the quantity and integrity of the RNA and different biomarkers derived from BTM through qPCR. Additionally, we performed the Banff Human Organ Transplant (B-HOT) panel on BTM from clinical biopsies using the NanoString nCounter platform as a proof-of-concept study. Results: Our results showed that the storage times ranging from 0.5 hours to 24 hours did not significantly affect RNA quality and yield. Differential gene expression analysis on allograft rejection BTM described specific profiles related to rejection. A significant correlation was observed between rejection-related transcripts and the corresponding Banff lesion scores.\u0000Conclusion: This study validated that the BTM can provide transcriptomic information relevant to the state of the kidney. The proof-of-concept study demonstrated that BTM has great potential for reflecting the status of the transplanted kidney. Tailored qPCR panels could allow for fast (same-day) molecular diagnosis.","PeriodicalId":501471,"journal":{"name":"bioRxiv - Pathology","volume":"78 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141873385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-26DOI: 10.1101/2024.07.23.602498
Nathan Gillespie, Michael C Neale, Matthew S Panizzon, Ruth E McKenzie, Xin M Tu, Chandra M Reynolds, Michael J Lyons, Robert A. Rissman, Jeremy A Elman, Carol E Franz, William S Kremen
INTRODUCTION: The amyloid cascade hypothesis predicts that amyloid-beta (Aβ) aggregation drives tau tangle accumulation. We tested competing causal non-causal hypotheses regarding the direction of causation between Aβ40 and Aβ42 and total Tau (t-Tau) plasma biomarkers. METHODS: Plasma Aβ40, Aβ42, t-Tau, and neurofilament light chain (NFL) were measured in 1,035 men (mean age 67.0 years, range 60-73) using Simoa Human Neurology 3-plex A Immunoassay assay. Genetically informative twin modeling tested the direction causation between Aβ and t-Tau. RESULTS: No conclusive evidence supported a causal impact of Aβ40 or Aβ42 on t-Tau. Exploratory analyses suggested Aβ biomarkers causally influence NFL, with reciprocal causation between t-Tau and NFL. DISCUSSION: Plasma Aβ40 and Aβ42 levels do not appear to causally impact t-Tau. However, Aβ aggregation may causally affect NFL in cognitively unimpaired, community-dwelling men around age 67.
{"title":"Testing the causal impact of amyloidosis on total Tau using a genetically informative sample of adult male twins.","authors":"Nathan Gillespie, Michael C Neale, Matthew S Panizzon, Ruth E McKenzie, Xin M Tu, Chandra M Reynolds, Michael J Lyons, Robert A. Rissman, Jeremy A Elman, Carol E Franz, William S Kremen","doi":"10.1101/2024.07.23.602498","DOIUrl":"https://doi.org/10.1101/2024.07.23.602498","url":null,"abstract":"INTRODUCTION: The amyloid cascade hypothesis predicts that amyloid-beta (Aβ) aggregation drives tau tangle accumulation. We tested competing causal non-causal hypotheses regarding the direction of causation between Aβ40 and Aβ42 and total Tau (t-Tau) plasma biomarkers. METHODS: Plasma Aβ40, Aβ42, t-Tau, and neurofilament light chain (NFL) were measured in 1,035 men (mean age 67.0 years, range 60-73) using Simoa Human Neurology 3-plex A Immunoassay assay. Genetically informative twin modeling tested the direction causation between Aβ and t-Tau. RESULTS: No conclusive evidence supported a causal impact of Aβ40 or Aβ42 on t-Tau. Exploratory analyses suggested Aβ biomarkers causally influence NFL, with reciprocal causation between t-Tau and NFL. DISCUSSION: Plasma Aβ40 and Aβ42 levels do not appear to causally impact t-Tau. However, Aβ aggregation may causally affect NFL in cognitively unimpaired, community-dwelling men around age 67.","PeriodicalId":501471,"journal":{"name":"bioRxiv - Pathology","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141775356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-26DOI: 10.1101/2024.07.25.605155
Emma Louise Fairbanks, Michael J Tildesley, Janet M Daly
Culicoides biting midges are significant vectors of various pathogens, impacting both human and animal health globally. Understanding their host feeding patterns is crucial for deepening our understanding of disease transmission dynamics and developing effective control strategies. While several studies have identified the sources of blood meals in Culicoides, a quantitative synthesis of their host preferences and the factors influencing these behaviours is lacking. A systematic literature search focused on gathering data on (1) host selection and (2) host preference. For reviewing host selection we focused on studies reporting the identification of blood meal sources in individual Culicoides. When reviewing host preference we focused on studies comparing the number of Culicoides caught on or nearby different host species at the same location. Analysis revealed that some Culicoides species exhibit fixed host preferences, consistently feeding on specific hosts such as cattle and horses, while others display more opportunistic feeding behaviours. Notable variations were observed across different geographic regions. The findings indicate that host availability significantly influences Culicoides feeding patterns. This study highlights the complexity of host selection in Culicoides biting midges, which has implications for disease transmission. The variability in feeding behaviours underscores the need for regional assessments to inform targeted vector control strategies.
{"title":"A systematic review quantifying host feeding patterns of Culicoides species responsible for pathogen transmission","authors":"Emma Louise Fairbanks, Michael J Tildesley, Janet M Daly","doi":"10.1101/2024.07.25.605155","DOIUrl":"https://doi.org/10.1101/2024.07.25.605155","url":null,"abstract":"<em>Culicoides</em> biting midges are significant vectors of various pathogens, impacting both human and animal health globally. Understanding their host feeding patterns is crucial for deepening our understanding of disease transmission dynamics and developing effective control strategies. While several studies have identified the sources of blood meals in <em>Culicoides</em>, a quantitative synthesis of their host preferences and the factors influencing these behaviours is lacking. A systematic literature search focused on gathering data on (1) host selection and (2) host preference. For reviewing host selection we focused on studies reporting the identification of blood meal sources in individual <em>Culicoides</em>. When reviewing host preference we focused on studies comparing the number of <em>Culicoides</em> caught on or nearby different host species at the same location. Analysis revealed that some <em>Culicoides</em> species exhibit fixed host preferences, consistently feeding on specific hosts such as cattle and horses, while others display more opportunistic feeding behaviours. Notable variations were observed across different geographic regions. The findings indicate that host availability significantly influences <em>Culicoides</em> feeding patterns. This study highlights the complexity of host selection in <em>Culicoides</em> biting midges, which has implications for disease transmission. The variability in feeding behaviours underscores the need for regional assessments to inform targeted vector control strategies.","PeriodicalId":501471,"journal":{"name":"bioRxiv - Pathology","volume":"286 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141775357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-24DOI: 10.1101/2024.07.19.604384
Ashley Duplessis, Christin Elster, Stefanie Becher, Christina Engel, Alexander Lang, Madlen Kaldirim, Christian Jung, Maria Grandoch, Malte Kelm, Susanne Pfeiler, Norbert Gerdes
Background: Determination of infarct area and scar size following myocardial infarction (MI) is commonly used to evaluate the efficacy of potential cardioprotective treatments in mice and other animal models. Methods: For both, early and late time points following MI, we compared classical histochemical approaches with fluorescence staining methods. Reperfused MI was induced in male C57BL/6J mice and hearts were extracted 24 hours, 7-, 21-, or 28-days following MI and stained with 2,3,5-Triphenyltetrazolium chloride (TTC) and Evans Blue, Hoechst, phalloidin, Sirius Red, Masson's or Gomori's Trichrome or Wheat Germ Agglutinin (WGA). Results: Fluorescent staining combining Hoechst and phalloidin constitutes an alternative for TTC and Evans Blue, enabling a clear visualization of infarct area, area at risk, as well as remote area unaffected by MI. Infarct size early after reperfusion determined with TTC staining correlates strongly with that demarcated by phalloidin while combination of Hoechst and phalloidin staining can emulate classical TTC/Evans Blue staining 24 h post-MI. Moreover, WGA is equally accurate as the classical Sirius Red, Masson's and Gomori's Trichrome stainings in identifying scar size in later phases (>7d) post-MI. Finally, we demonstrate feasibility of combining conventional fluorescence staining by localizing CD45+ leukocytes to specific regions of the infarcted myocardium. Conclusion: We established staining procedure is not inferior to classical TTC staining while providing substantial benefits including the option for unbiased software-assisted analysis while sparing ample residual tissue for additional analyses. Overall, this enhances the data quality and reduces the required animal numbers consistent with the 3R concept of animal experimentation.
{"title":"Novel fluorescence-based methods to determine infarct and scar size in murine models of reperfused myocardial infarction","authors":"Ashley Duplessis, Christin Elster, Stefanie Becher, Christina Engel, Alexander Lang, Madlen Kaldirim, Christian Jung, Maria Grandoch, Malte Kelm, Susanne Pfeiler, Norbert Gerdes","doi":"10.1101/2024.07.19.604384","DOIUrl":"https://doi.org/10.1101/2024.07.19.604384","url":null,"abstract":"Background: Determination of infarct area and scar size following myocardial infarction (MI) is commonly used to evaluate the efficacy of potential cardioprotective treatments in mice and other animal models.\u0000Methods: For both, early and late time points following MI, we compared classical histochemical approaches with fluorescence staining methods. Reperfused MI was induced in male C57BL/6J mice and hearts were extracted 24 hours, 7-, 21-, or 28-days following MI and stained with 2,3,5-Triphenyltetrazolium chloride (TTC) and Evans Blue, Hoechst, phalloidin, Sirius Red, Masson's or Gomori's Trichrome or Wheat Germ Agglutinin (WGA). Results: Fluorescent staining combining Hoechst and phalloidin constitutes an alternative for TTC and Evans Blue, enabling a clear visualization of infarct area, area at risk, as well as remote area unaffected by MI. Infarct size early after reperfusion determined with TTC staining correlates strongly with that demarcated by phalloidin while combination of Hoechst and phalloidin staining can emulate classical TTC/Evans Blue staining 24 h post-MI. Moreover, WGA is equally accurate as the classical Sirius Red, Masson's and Gomori's Trichrome stainings in identifying scar size in later phases (>7d) post-MI. Finally, we demonstrate feasibility of combining conventional fluorescence staining by localizing CD45+ leukocytes to specific regions of the infarcted myocardium.\u0000Conclusion: We established staining procedure is not inferior to classical TTC staining while providing substantial benefits including the option for unbiased software-assisted analysis while sparing ample residual tissue for additional analyses. Overall, this enhances the data quality and reduces the required animal numbers consistent with the 3R concept of animal experimentation.","PeriodicalId":501471,"journal":{"name":"bioRxiv - Pathology","volume":"94 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141775408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-24DOI: 10.1101/2024.07.23.604797
hui yang, Yu Shu Xu, Yu Shan Zhao, Yin Ping Shu, Xin Sun, Jun Bo Du
Plasmodiophora brassicae causes a significant global threat to cruciferous vegetables and crops. However, the current comprehensions of its pathogenic ways is still unclear. This study identified a P. brassicae effector, called PbEGF1, which strongly induces cell death in N. benthamiana. Notably, PbEGF1 was significantly up-regulated in seedlings inoculated with highly virulent P. brassicae, indicating a pivotal role for PbEGF1 in pathogenicity. Furthermore, overexpression of PbEGF1 in hosts enhanced susceptibility to P. brassicae, and promoted elongation of root hairs, thus creating favorable conditions for root hair infection. Silencing of PbEGF1 reduced the pathogenicity of P. brassicae. This finding confirms the significance of primary infection in host recognition and interaction with P. brassicae. To further elucidate the virulence function of PbEGF1, we identified BnNHL13 (nonrace- specific disease resistance 1/harpin-induced 1-like 13) as its target protein. Silencing BnNHL13 enhanced host susceptibility to P. brassicae, and promoted root hairs elongation, indicating that down-regulation of BnNHL13 was more conducive to establishing P. brassicae infection. Subsequent investigation revealed that PbEGF1 has the ability to induce degradation of the BnNHL13 protein, thereby disrupting the host defense response and facilitating P. brassicae infection. Our findings provide novel insights into genetic strategies for enhancing plant resistance against clubroot disease.
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