scholarly journals Individual copy number variation and extensive diversity between major MHC-DAB1 allelic lineages in the European bitterling

2022 ◽  
Author(s):  
Lorenzo Talarico ◽  
Anna Bryjová ◽  
Dagmar Čížková ◽  
Karel Douda ◽  
Martin Reichard
Keyword(s):  
Balancing Selection ◽  
Amplicon Sequencing ◽  
Synonymous Mutations ◽  
Allelic Lineages ◽  
Histocompatibility Complex ◽  
Number Variation ◽  
Long Time ◽  
Host Parasite ◽  
First Time

AbstractPolymorphism of the major histocompatibility complex (MHC), DAB1 gene was characterized for the first time in the European bitterling (Rhodeus amarus), a freshwater fish employed in studies of host-parasite coevolution and mate choice, taking advantage of newly designed primers coupled with high-throughput amplicon sequencing. Across 221 genotyped individuals, we detected 1–4 variants per fish, with 28% individuals possessing 3–4 variants. We identified 36 DAB1 variants, and they showed high sequence diversity mostly located within predicted antigen-binding sites, and both global and codon-specific excess of non-synonymous mutations. Despite deep divergence between two major allelic lineages, functional diversity was surprisingly low (3 supertypes). Overall, these findings suggest the role of positive and balancing selection in promotion and long-time maintenance of DAB1 polymorphism. Further investigations will clarify the role of pathogen-mediated selection to drive the evolution of DAB1 variation.

scholarly journals Clinical significance of late diastolic tissue doppler parameters after onset of STEMI: from the view point of the timing of the echocardipography

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Iwahashi ◽  
J Kirigaya ◽  
M Horii ◽  
T Abe ◽  
E Akiyama ◽  
...  
Keyword(s):  
Tissue Doppler ◽  
Atrial Function ◽  
Diastolic Velocity ◽  
Long Time ◽  
Group A ◽  
St Elevation ◽  
Group B ◽  
First Time

Abstract Background The early transmitral flow velocity (E) divided by the early diastolic velocity of the mitral valve annulus (e') is referred to as the “E/e' ratio,” is useful even for ST elevation acute myocardial infarction (STEMI). However, the role of late diastolic velocity (a') which reveals the atrial function for STEMI is still unclear. Objectives We evaluated the clinical usefulness of tissue Doppler including atrial function for a first-time STEMI by long time follow up. Furthermore, we evaluated the meaning of each parameters by performing immediately after PCI or 2 weeks later. Methods We treated consecutive 571 first-time STEMI patients by immediate PCI within 12 hours after onset, and we examined 270 patients at immediately after PCI (GroupA, 65 years, 250 male) and 301 patients at 2 weeks after onset (GroupB, 64 years, 243 male). We examined trans mitral flow and TDI, then defined E/e' as LV filling pressure and A/a' as left atrial function. We followed them for a long time (>5 years). The primary end point (PE) was cardiac death or re-admission for heart failure (HF). Results We followed the patients in Group A for 10 years, Group B for 5 years. PE occurred in 64 patients in GroupA during 10 years, and 45 patients in GroupB during 5 years. We analyzed the univariate and multivariate Cox hazard analyses and we compared e' and a', E/e' and A/a' (Table). In GroupA, a' and A/a' were the independent predictors, on the other hand neither a' nor A/a' were the predictors in GroupB. E/e' was an independent predictor both in GroupA and B. Conclusion TDI parameters have different meanings by the timing of echocardiography after onset of a first-time STEMI. These results demonstrated that atrial dysfunction immediately after onset of STEMI suggests the poor prognosis after STEMI. Cox Hazard Proportional Analysis Funding Acknowledgement Type of funding source: None

scholarly journals Modulation of Dendritic Cell Apoptosis and CD8+Cytotoxicity by Histamine: Role of Protein Kinase C

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Julieta Alcain ◽  
Enrique Podaza ◽  
María Soledad Gori ◽  
Gabriela Salamone ◽  
Mónica Vermeulen
Keyword(s):  
T Lymphocytes ◽  
Inflammatory Responses ◽  
Cytolytic Activity ◽  
Cross Presentation ◽  
Kinase C ◽  
Histocompatibility Complex ◽  
First Time ◽  
G Protein Coupled ◽  
Pkc Activation

Dendritic cells (DC) are able to present extracellular antigens associated with the molecules of the major histocompatibility complex class I. In a previous work, we demonstrated that the histamine (HIS), acting through H1/H4 receptors, increases the cross-presentation of soluble ovalbumin by murine DC and can enhance the recruitment of specific CD8+T lymphocytes during the development of chronic inflammatory responses. Here, we studied in more depth the mechanisms underlying this enhancement. We showed that the cytotoxicity of specific CD8+lymphocytes is increased in HIS-treated DC and it is lost by inhibition of vacuolar-ATPase that prevents endosome acidification. It is known that HIS acts through G protein-coupled receptors. The H1/H4 receptors are associated with a Gqsubunit, which involves PKC signaling, a pathway related to the apoptotic process. Interestingly, we demonstrated for the first time that HIS prevents DC apoptosis induced by heat shock through the inhibition of caspase-3, a mechanism dependent on PKC activation, since it is reversed by its inhibition. By contrast, cytolytic activity of T lymphocytes induced by HIS-stimulated DC was independent of PKC pathway.

scholarly journals Restoration of a tumorigenic phenotype by beta 2-microglobulin transfection to EL-4 mutant cells.

1992 ◽  
Vol 175 (3) ◽  
pp. 843-846 ◽  
Author(s):  
R Glas ◽  
K Sturmhöfel ◽  
G J Hämmerling ◽  
K Kärre ◽  
H G Ljunggren
Keyword(s):  
Transfected Cells ◽  
Histocompatibility Complex ◽  
Tumorigenic Potential ◽  
Immunological Recognition ◽  
Beta 2 ◽  
Beta 2 Microglobulin ◽  
First Time ◽  
Mutant Cells

It has frequently been suggested that loss of beta 2-microglobulin (beta 2m) in tumor cells may lead to malignant progression due to escape from immunological recognition. Here, we directly tested the role of beta 2m expression in tumorigenicity. A beta 2 m loss mutant (C4.4-25-), selected from the murine lymphoma EL-4, showed a marked reduction in tumorigenicity as compared with EL-4 in normal C57B1/6 (B6) mice. The reduced tumorigenicity was directly related to beta 2 m expression. Transfection of an intact murine beta 2m gene markedly increased the tumorigenic potential. The reduced tumorigenicity of C4.4-25- compared with beta 2m transfected cells was observed also in athymic B6 nu/nu mice, but was abolished in B6 mice depleted of natural killer (NK) 1.1-positive cells. These results show that restoration of beta 2m expression can promote tumorigenicity and demonstrate for the first time that induction of major histocompatibility complex class I expression by transfection can lead to escape from NK cells in vivo.

Autoantigenic Targets of B-Cell Receptors (BCR) Derived From Chronic Lymphocytic Leukemias Bind to and Induce Proliferation of Leukemic Cells.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2884-2884
Author(s):  
Klaus-Dieter Preuss ◽  
Gerhard Held ◽  
Natalie Fadle ◽  
Evi Regitz ◽  
Maria Kemele ◽  
...  
Keyword(s):  
B Cell ◽  
Conflicts Of Interest ◽  
Specific Binding ◽  
Cell Receptor ◽  
Convincing Evidence ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Long Time ◽  
First Time

Abstract Abstract 2884 Background Auto-antigenic targets of the B-cell receptor (BCR) derived from malignant cells in chronic lymphocytic leukemia (CLL) might play a role in the pathogenesis of this neoplasm. Patients and Methods In order to identify autoantigenic targets of CLL-derived BCR we screened human tissue-derived protein macroarrays with Fab fragments obtained by papain treatment of CLL cells derived from 50 consecutive cases. Antigens were biochemically and molecularly characterized and recombinantly expressed. Results An autoantigenic target was identified for 12/50 (24%) of the cases, with 3 autoantigens being the target of the BCR from two patients each. CLL-BCR derived from the same stereotype subset recognized the same antigen, but differed epitopes. By flow cytometry using flag-tagged recombinantly expressed autoantigens binding of antigen to the surface of CLL was demonstrated, which was specific for the CLL cells from which the BCR used for the identification of the respective autoantigen was derived. Moreover, binding of the autoantigen to the respective leukemic cells induced specific activation as shown by increased cytoplasmic calcium concentration, induced MYC expression and proliferation of leukemic CLL cells as demonstrated by a proliferation assay (EZ4U). Conclusions Autoantigens are frequent targets of CLL-derived BCR. Their specific binding to and induction of proliferation in respective leukemic cells, which has been demonstrated for the first time, provide the most convincing evidence to date for the long-time hypothesized role of autoantigens in the pathogenesis of chronic lymphocyte leukemia. Supported by Sander-Stiftung (Munich, Germany) Disclosures: No relevant conflicts of interest to declare.

scholarly journals The role of the gut microbiome during host ageing

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1086 ◽  
Author(s):  
Jens Seidel ◽  
Dario Riccardo Valenzano
Keyword(s):  
Gut Microbiota ◽  
Microbial Communities ◽  
Model Organisms ◽  
Intestinal Microbes ◽  
Long Time ◽  
Key Aspects ◽  
And Function ◽  
Open Question ◽  
First Time

Gut microbial communities participate in key aspects of host biology, including development, nutrient absorption, immunity and disease. During host ageing, intestinal microbes undergo dramatic changes in composition and function and can shift from commensal to pathogenic. However, whether they play a causal role in host ageing and life span has remained an open question for a long time. Recent work in model organisms has revealed for the first time that gut microbes can modulate ageing, opening new questions and opportunities to uncover novel ageing-modulating mechanisms and to design anti-ageing interventions by targeting the gut microbiota.

Co-occurrence of Eutrombicula alfreddugesi and Oswaldofilaria chabaudi in Tropidurus torquatus and first report of microfilariae in the chigger mite: possible evidence of a lifecycle pathway?

2021 ◽  
Vol 95 ◽  
Author(s):  
P.V. Alves ◽  
S.C. Gomides ◽  
F.B. Pereira
Keyword(s):  
Current Evidence ◽  
Chigger Mite ◽  
Blood Sucking ◽  
Dead End ◽  
Filarial Nematodes ◽  
Vector Borne ◽  
Host Parasite ◽  
First Time ◽  
Trombiculid Mites

Abstract While much attention has been paid to vector-borne filariasis, diseases that threaten millions of people in tropical and subtropical countries, the literature on host–parasite associations and transmission strategies of filarial nematodes in wildlife is scarce. Here, we report the co-occurrence of chigger mites (Eutrombicula alfreddugesi) and onchocercid nematodes (Oswaldofilaria chabaudi) parasitizing the lizard Tropidurus torquatus in the State of Minas Gerais, Brazil. Examination of chiggers established, for the first time, the occurrence of microfilariae in trombiculid mites (Trombiculidae). These larvae were morphologically similar to those recovered from adult females of O. chabaudi. The current evidence suggests that chiggers do not play a role in the transmission of filarioid nematodes, but rather act as accidental or dead-end hosts. Nevertheless, considering the polyphagous nature of trombiculid mites, similar to blood-sucking insects involved in the transmission of several infectious diseases, further studies may shed light on the potential role of chiggers as vectors of filarioids.

scholarly journals THE ROLE OF THE HUNGARIAN SAMIZDAT IN INTENSIFYING OF OPPOSITION-MINDED PUBLIC (1976 – 1988)

2017 ◽  
pp. 66-72
Author(s):  
M. Junger
Keyword(s):  
Positive Impact ◽  
Deep Understanding ◽  
Central Committee ◽  
Popular Front ◽  
Political Pluralism ◽  
Urban Group ◽  
Hungarian Society ◽  
Long Time ◽  
First Time

The paper reviews the origins and development of samizdat in the Hungarian People's Republic. The samizdat for a long time remained the only way of doing opposition activities. It contributed to the spread of uncensored information and dissident's consolidation. The main opposition groups were urban and populist. The principle of the "popular front", which had deep historical roots in Hungary, meant joint efforts of various actors. It played an important role for their consolidation during the work on the collection of papers "In Memory of Bibo". The authors questioned the legitimacy of socialist states in Central and Eastern Europe. They had also written a program for achievement political pluralism, multi-party democracy. There was a positive impact of the political legacy of the philosopher to the ideological development of the urban group. The reaction of the Central Committee of the Hungarian Socialist Workers' Party to the "In Memory of Bibo" testified a deep understanding of the causes of origin and prospects of the opposition's growth. Thematic areas of the leading samizdat journals "Beszélő", "Hirmondó", "Demokrata", their contribution to the consolidation of opposition-minded part of the Hungarian society were estimated. In this paper for the first time in the Ukrainian historiography we gave an account on the image of the Ukrainian dissident movement in the Hungarian samizdat.

scholarly journals Detection of classic and cryptic Strongyloides genotypes by deep amplicon sequencing: A preliminary survey of dog and human specimens collected from remote Australian communities

2019 ◽  
Author(s):  
Meruyert Beknazarova ◽  
Joel L. N. Barratt ◽  
Richard S. Bradbury ◽  
Meredith Lane ◽  
Harriet Whiley ◽  
...  
Keyword(s):  
Sputum Sample ◽  
Strongyloides Stercoralis ◽  
Amplicon Sequencing ◽  
Socioeconomically Disadvantaged ◽  
Remote Communities ◽  
Disadvantaged Communities ◽  
The North ◽  
Potential Reservoir ◽  
First Time

AbstractStrongyloidiasis is caused by the human infective nematodes Strongyloides stercoralis, Strongyloides fuelleborni subsp. fuelleborni and Strongyloides fuelleborni subsp. kellyi. The zoonotic potential of S. stercoralis and the potential role of dogs in the maintenance of strongyloidiasis transmission has been a topic of interest and discussion for many years. In Australia, strongyloidiasis is prevalent in remote socioeconomically disadvantaged communities in the north of the continent. Being an isolated continent that has been separated from other regions for a long geological period, description of the diversity of Australian Strongyloides genotypes adds to our understanding of the genetic diversity within the genus. Using PCR enrichment combined with Illumina sequencing technology, we sequenced the Strongyloides SSU 18S rDNA hyper-variable I and hyper-variable IV regions using Strongyloides-specific primers, and a fragment of the mtDNA cox1 gene using primers that are broadly specific for Strongyloides sp. and hookworms. These loci were amplified from DNA extracted from Australian human and dog faeces, and one human sputum sample. Using this approach, we confirm for the first time that potentially zoonotic S. stercoralis genotypes are present in Australia, suggesting that dogs represent a potential reservoir of human strongyloidiasis in remote Australian communities.Author summaryStrongyloides stercoralis is a soil-transmitted nematode that causes the disease strongyloidiasis. Due to the autoinfective nature of this parasite, it can re-infect a host causing chronic infection. If not diagnosed and treated it can be highly detrimental to human health and has a high mortality rate. Strongyloidiasis is common in remote communities in the north of Australia and has been an issue for decades. Despite various successful intervention programs to treat human strongyloidiasis, the disease remains endemic in those communities. Here for the first time we looked at the Australian dogs’ potential to infect humans and found that they carry two genetically distinct strains of Strongyloides spp., one of which also infects humans. This supports the hypothesis that dogs are a potential source for human strongyloidiasis. We also found that dogs in Australia might be carrying unique haplotypes. Whether these new haplotypes are also human infective is to be confirmed by further research.

scholarly journals Emergence and diversification of a host-parasite RNA ecosystem through Darwinian evolution

2019 ◽  
Author(s):  
Taro Furubayashi ◽  
Kensuke Ueda ◽  
Yohsuke Bansho ◽  
Daisuke Motooka ◽  
Shota Nakamura ◽  
...  
Keyword(s):  
Darwinian Evolution ◽  
Prebiotic Evolution ◽  
Clonal Population ◽  
Replication Errors ◽  
Replication Experiment ◽  
Living Organisms ◽  
Host Parasite ◽  
First Time

AbstractIn the prebiotic evolution, molecular self-replicators are considered to develop into diverse, complex living organisms. The appearance of parasitic replicators is believed inevitable in this process. However, the role of parasitic replicators on prebiotic evolution remains elusive. Here, we demonstrated experimental coevolution of RNA self-replicators (host RNAs) and emerging parasitic replicators (parasitic RNAs) for the first time by using an RNA-protein replication system we had developed. During a long-term replication experiment, a clonal population of the host RNA turned into an evolving host-parasite ecosystem through the continuous emergence of new types of host and parasitic RNAs produced by replication errors. The diversified host and parasitic RNAs exhibited evolutionary arms-race dynamics. The parasitic RNA accumulated unique mutations that the host RNA had never acquired, thus adding a new genetic variation to the whole replicator ensemble. These results provide the first experimental evidence that the coevolutionary interplay between host-parasite molecules play a key role in generating diversity and complexity in prebiotic molecular evolution.

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