- MeSH
- Cryptosporidium parvum pathogenicity MeSH
- Disease Models, Animal MeSH
- Mice parasitology physiopathology MeSH
- Opportunistic Infections MeSH
- Protozoan Infections physiopathology MeSH
- Animals MeSH
- Check Tag
- Mice parasitology physiopathology MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Comparative Study MeSH
The previously developed mathematical model of CD4+ lymphocyte dynamics in HIV infection incorporated a homeostatic mechanism regulating production of both CD4+ and CD8+ lymphocytes. The model simulated the CD4+ lymphocyte dynamics well, but simulation of CD8+ lymphocyte values was not satisfactory, because simulated numbers of these cells increased even at later stages of infection, when no further increase was observed in infected individuals. Modifications of the model were attempted to obtain better simulation results assuming the influence of HIV infection on CD8+ lymphocyte maturation. Satisfactory results were obtained, if the influx of immature CD4+ and CD8+ lymphocytes was constrained by HIV infection. This modified version was then used for simulation of the anti-CD8 antibody administration effect in HIV-infected persons.
- MeSH
- CD8-Positive T-Lymphocytes immunology MeSH
- HIV Infections immunology MeSH
- Humans MeSH
- Mathematical Computing * MeSH
- Models, Immunological * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Ascariasis immunology MeSH
- Eosinophils MeSH
- Mice MeSH
- Antibodies MeSH
- Trichinellosis immunology MeSH
- Check Tag
- Mice MeSH
Molecular dynamics simulations of complexes between Norwalk virus RNA dependent RNA polymerase and its natural CTP and 2dCTP (both containing the O5'-C5'-C4'-O4' sequence of atoms bridging the triphosphate and sugar moiety) or modified coCTP (C5'-O5'-C4'-O4'), cocCTP (C5'-O5'-C4'-C4'') substrates were produced by means of CUDA programmable graphical processing units and the ACEMD software package. It enabled us to gain microsecond MD trajectories clearly showing that similar nucleoside triphosphates can bind surprisingly differently into the active site of the Norwalk virus RNA dependent RNA polymerase. It corresponds to their different modes of action (CTP-substrate, 2dCTP-poor substrate, coCTP-chain terminator, cocCTP-inhibitor). Moreover, extremely rare events-as repetitive pervasion of Arg182 into a potentially reaction promoting arrangement-were captured.
- MeSH
- Cytidine Triphosphate analogs & derivatives metabolism MeSH
- Caliciviridae Infections virology MeSH
- Humans MeSH
- Norovirus enzymology metabolism MeSH
- RNA-Dependent RNA Polymerase metabolism MeSH
- Molecular Dynamics Simulation MeSH
- Molecular Docking Simulation MeSH
- Substrate Specificity MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
While pathogens are often assumed to limit the growth of wildlife populations, experimental evidence for their effects is rare. A lack of food resources has been suggested to enhance the negative effects of pathogen infection on host populations, but this theory has received little investigation. We conducted a replicated two-factor enclosure experiment, with introduction of the bacterium Bordetella bronchiseptica and food supplementation, to evaluate the individual and interactive effects of pathogen infection and food availability on vole populations during a boreal winter. We show that prior to bacteria introduction, vole populations were limited by food availability. Bordetella bronchiseptica introduction then reduced population growth and abundance, but contrary to predictions, primarily in food supplemented populations. Infection prevalence and pathological changes in vole lungs were most common in food supplemented populations, and are likely to have resulted from increased congregation and bacteria transmission around feeding stations. Bordetella bronchiseptica-infected lungs often showed protozoan co-infection (consistent with Hepatozoon erhardovae), together with more severe inflammatory changes. Using a multidisciplinary approach, this study demonstrates a complex picture of interactions and underlying mechanisms, leading to population-level effects. Our results highlight the potential for food provisioning to markedly influence disease processes in wildlife mammal populations.
- MeSH
- Arvicolinae * MeSH
- Bordetella bronchiseptica physiology MeSH
- Diet veterinary MeSH
- Bordetella Infections microbiology veterinary MeSH
- Random Allocation MeSH
- Rodent Diseases microbiology MeSH
- Population Dynamics MeSH
- Population Growth MeSH
- Dietary Supplements analysis MeSH
- Seasons MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Finland MeSH
The shape and number of mitochondria respond to the metabolic needs during the cell cycle of the eukaryotic cell. In the best-studied model systems of animals and fungi, the cells contain many mitochondria, each carrying its own nucleoid. The organelles, however, mostly exist as a dynamic network, which undergoes constant cycles of division and fusion. These mitochondrial dynamics are driven by intricate protein machineries centered around dynamin-related proteins (DRPs). Here, we review recent advances on the dynamics of mitochondria and mitochondrion-related organelles (MROs) of parasitic protists. In contrast to animals and fungi, many parasitic protists from groups of Apicomplexa or Kinetoplastida carry only a single mitochondrion with a single nucleoid. In these groups, mitochondrial division is strictly coupled to the cell cycle, and the morphology of the organelle responds to the cell differentiation during the parasite life cycle. On the other hand, anaerobic parasitic protists such as Giardia, Entamoeba, and Trichomonas contain multiple MROs that have lost their organellar genomes. We discuss the function of DRPs, the occurrence of mitochondrial fusion, and mitophagy in the parasitic protists from the perspective of eukaryote evolution.
- MeSH
- Mitochondrial Dynamics * MeSH
- Parasitic Diseases epidemiology parasitology physiopathology MeSH
- Parasites pathogenicity MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
V souboru 92 pacientů s diagnózou neuroboreliózy byla metodou průtokové cytofluorometrie studována dynamika lymfocytárních subpopulací a její závislost na typu a stupni závažnosti klinického postižení. Sledovali jsme absolutní a relativní počty celkových T a B lymfocytů, pomocných a cytotoxických/supresorových T lymfocytů a NK buněk před léčbou infekce Borrelia burgdorferi, krátce po léčbě a v období 3 a 6 měsíců po terapii. Nejvýraznější statisticky významné změny (p < 0,001) byly pozorovány u B lymfocytů a NK buněk. B lymfocyty vykazovaly v akutní fázi nemoci výrazně vyšší absolutní i relativní počty než po přeléčení. Naopak absolutní i relativní počty NK buněk významně vzrostly v průběhu rekonvalescence. Menší statistickou významnost (p < 0,05) měly změny ostatních podříd T lymfocytů. Absolutní počty celkových T lymfocytů po léčbě přechodně klesly, což bylo způsobeno hlavně poklesem pomocných T lymfocytů, absolutní počty cytotoxických/supresorových buněk vykázaly mírný vzrůst v rekonvalescenci. Neprokázali jsme statisticky významnou korelaci v počtu pomocných a cytotoxických/supresorových T lymfocytů v závislosti na závažnosti onemocnění. U pacientů s meningopolyradikuloneuritidou byl zaznamenán prokazatelně vyšší slav celkových a pomocných T lymfocytů než u pacientů s akutní encefalitidou. Po zhodnocení vývoje lymfocytárních subpopulací se ukázalo, že sledované parametry nelze jednoznačně použít při určování diagnózy, prognózy a v léčbě pacientů s neuroboreliózou.
In a group of 92 patients with a diagnosis of neuroborreliosis, using the flow cytofluorometry method, the dynamics of lymphocyte subpopulations and its relation to the type and severity of clinical affliction was investigated. We observed the absolute and relative counts of total T and B lymphocytes, helper and cytotoxic/suppressor T lymphocytes, and NK cells before and shortly after treatment of Borrelia burgdorferi infection, and in the period of 3 and 6 months following therapy. The most statistically significant changes (p < 0.00l) were observed in B lymphocytes and NK cells. B lymphocytes showed in the acute stage of the disease markedly higher absolute and relative counts than after treatment. In contrast, absolute and relative counts of NK cells incerased significantly during convalescence. Of statistically lesser significance (p < 0.05) were changes in the other T lymphocyte subpopulations. Absolute counts of total T lymphocytes after treatment dropped transiently, this was caused chiefly by the decrease of helper T lymphocyte counts; absolute counts of cytotoxic/suppressor cells showed a moderate increase during convalescence. We did not find a statistically significant correlation of the counts of helper and cytotoxic/suppressor T lymphocytes in dependence with the gravity of the disease. In patients with meningopolyradiculoneuritis, a demonstrably higher count of total and helper T lymphocytes was detected than in patients with acute encephalitits. After assessing the development of lymphocte subpopulations it was shown that the investigated parameters cannot be used because of unequivocal determination of the diagnosis, prognosis, and treatment of patients with neuroborreliosis.
- MeSH
- Culicidae MeSH
- Filarioidea MeSH
- Filariasis transmission MeSH
- Humans MeSH
- Disease Reservoirs MeSH
- Check Tag
- Humans MeSH
- Male MeSH
SARS-CoV-2 cause fatal infection in 213 countries accounting for the death of millions of people globally. In the present study, phytochemicals from spices were assessed for their ability to interact with SARS-CoV-2 MPro. Structure based virtual screening was performed with 146 phytochemicals from spices using Autodock Vina. Phytochemicals with binding energy ≥ -8.0 kcal/mol were selected to understand their interaction with MPro. Virtual screening was further validated by performing molecular docking to generate favorable docked poses and the participation of important amino acid residues. Molecular dynamics simulation for the docked poses was performed to study thermodynamic properties of the protein, ligand and protein-ligand complexes. The finding shows that cinnamtannin B2 and cyanin showed favorable binding affinity values with SARS-CoV-2 MPro. The results are comparable in terms of docked poses, important amino acid participation and thermodynamic properties with the standard control drugs remdesivir, benazepril and hydroxychloroquine diphosphate. Prime MM-GBSA was employed for end-point binding energy calculation. Binding to domain I and II of MPro were mediated through the OH, SH, NH2 and non-polar side chain of amino acids. Cinnamtannin B2 and cyanin binds to MPro with many sub sites within the active site with RMSD and RMSF within 4 Å. The results computed using Prime MM-GBSA show that cinnamtannin B2 (-68.54940214 kcal/mol) and cyanin (-62.1902835 kcal/mol) have better binding affinity in comparison to hydroxychloroquine diphosphate (-54.00912412 kcal/mol) and benazepril (-53.70242369 kcal/mol). The results provide a basis for exploiting cinnamtannin B2 and cyanin as a starting point potential candidate for the development of drug against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.
