Distinct genetic control of parasite elimination, dissemination, and disease after Leishmania major infection

Elimination of pathogens is the basis of host resistance to infections; however, relationship between persisting pathogens and disease has not been clarified. Leishmania major infection in mice is an important model of host–pathogen relationship. Infected BALB/c mice exhibit high parasite numbers in lymph nodes and spleens, and a chronic disease with skin lesions, splenomegaly, and hepatomegaly, increased serum IgE levels and cytokine imbalance. Although numerous gene loci affecting these disease symptoms have been reported, genes controlling parasites’ elimination or dissemination have never been mapped. We therefore compared genetics of the clinical and immunologic symptomatology with parasite load in (BALB/c × CcS-11) F2 hybrids and mapped five loci, two of which control parasite elimination or dissemination. Lmr5 influences parasite loads in spleens (and skin lesions, splenomegaly, and serum IgE, IL-4, and IFNγ levels), and Lmr20 determines parasite numbers in draining lymph nodes (and serum levels of IgE and IFNγ), but no skin or visceral pathology. Three additional loci do not affect parasite numbers but influence significantly the disease phenotype—Lmr21: skin lesions and IFNγ levels, Lmr22: IL-4 levels, Lmr23: IFNγ levels, indicating that development of L. major-caused disease includes critical regulations additional to control of parasite spread

Genetics of Host Response to Leishmania tropica in Mice – Different Control of Skin Pathology, Chemokine Reaction, and Invasion into Spleen and Liver

Several hundred million people are exposed to the risk of leishmaniasis, a disease caused by intracellular protozoan parasites of several Leishmania species and transmitted by phlebotomine sand flies. In humans, L. tropica causes cutaneous form of leishmaniasis with painful and long-persisting lesions in the site of the insect bite, but the parasites can also penetrate to internal organs. The relationship between the host genes and development of the disease was demonstrated for numerous infectious diseases. However, the search for susceptibility genes in the human population could be a difficult task. In such cases, animal models may help to discover the role of different genes in interactions between the parasite and the host. Unfortunately, the literature contains only a few publications about the use of animals for L. tropica studies. Here, we report an animal model suitable for genetic, pathological and drug studies in L. tropica infection. We show how the host genotype influences different disease symptoms: skin lesions, parasite dissemination to the lymph nodes, spleen and liver, and increase of levels of chemokines CCL2, CCL3 and CCL5 in serum

Genetic Control of Resistance to Trypanosoma brucei brucei Infection in Mice

Trypanosoma brucei are extracellular protozoa transmitted to mammalian host by the tsetse fly. They developed several mechanisms that subvert host's immune defenses. Therefore analysis of genes affecting host's resistance to infection can reveal critical aspects of host-parasite interactions. Trypanosoma brucei brucei infects many animal species including livestock, with particularly severe effects in horses and dogs. Mouse strains differ greatly in susceptibility to T. b. brucei. However, genes controlling susceptibility to this parasite have not been mapped. We analyzed the genetic control of survival after T. b. brucei infection using CcS/Dem recombinant congenic (RC) strains, each of which contains a different random set of 12.5% genes of their donor parental strain STS/A on the BALB/c genetic background. The RC strain CcS-11 is even more susceptible to parasites than BALB/c or STS/A. In F2 hybrids between BALB/c and CcS-11 we detected and mapped four loci, Tbbr1-4 (Trypanosoma brucei brucei response 1–4), that control survival after T. b. brucei infection. Tbbr1 (chromosome 3) and Tbbr2 (chromosome 12) have independent effects, Tbbr3 (chromosome 7) and Tbbr4 (chromosome 19) were detected by their mutual inter-genic interaction. Tbbr2 was precision mapped to a segment of 2.15 Mb that contains 26 genes

Elektro – optický monitoring citrátu sodného aplikovatelného v hemodialýze

V této práci se popisují naše počáteční experimenty ve vývoji „on-line“ senzoru na monitoring koncentrace citrátu sodného (Na3C6H2O7) v mimo mozkovém proudění krve v průběhu hemodialýzy. Přesný a rychlý monitoring by umožnil regulaci koncentrace citrátu a návrat do krevního řečiště těla v jeho původních hodnotách, tím pacienta významně méně zatíženého než v přítomnosti. Nedávno jsme se soustředili na stanovení koncentrace měřením elektrické impedance a odrazivosti ve zkoumané krvi. Našim cílem je zkoumat trendy vlivu těchto signálů na koncentraci a vyvinout vhodnou metodiku, která může být použita později v senzorech. Částečně začínáme pracovat také na citlivosti metodiky, přičemž bychom rádi výpočtem dosáhli ekvivalentní elektrický model řešení. To je založeno na elektrochemickém dvouvrstvém modelu a korespondenci s Cole-Cole grafyIn this paper, we describe our initial steps in the development of online sensor to monitor the tri-sodium citrate concentration in extra-cerebral blood flow during haemodialysis. Accurate and fast monitoring would allow the regulation of the concentration of citrate returning to the human bloodstream to its original values, thereby, making the patient significantly less burdened than at present. In the early stages, we focused on the determination of concentration by measuring of electrical impedance and reflection in the collected blood. Our aim is to study the trends of influencing these signals by concentration and to develop a suitable methodology that can be used later in the sensor. In part, we begin working on the selectivity of the methodology that we would like to achieve by calculating the equivalent electrical model of the solution. It is based on the electrochemical double layer model and the corresponding Cole-Cole graphs

Sub-fossil bark beetles as indicators of past disturbance events in temperate Picea abies mountain forests

Temperate mountain forests have experienced an increase in frequency and severity of natural disturbances (e.g., droughts, fires, windstorms and insect outbreaks) in recent decades due to climate and environmental change. Outbreaks of bark beetles have caused significant dieback of conifer forests in Central Europe and it is essential to model and predict the potential severity of future bark beetle outbreaks. However, to predict future bark beetle activity, historical baseline information is required to contextualize the magnitude of current and potential future outbreaks. A fossil beetle record from a forest hollow in the Tatra Mountains, Slovakia; one of the best-preserved national parks in Central Europe, was produced to identify insect outbreaks during the last millennia. Sub-fossil bark beetle remains were compared with parallel pollen and charcoal to assess whether peaks in conifer bark beetle remains correspond with indications of disturbance documented in historical or sedimentary fossil records. Three peaks in bark beetle remains were detected (1) post-2004, (2) AD 1140–1440, and (3) AD 930–1030. The abundance of species Pityogenes chalcographus and Pityophthorus pityographus in the two top samples can be linked directly to large bark beetle outbreaks in the High Tatra Mountains after 2004. P. chalcographus and P. pityographus are also the abundant species in the second peak (AD 1140–1440) while the third peak (AD 930–1030) consists of the species Polygraphus poligraphus. The most prominent conifer bark beetle in Central Europe, Ips typographus, was found to be present in most of the samples but always at very low numbers. It is plausible that P. chalcographus and P. pityographus fossils might be useful proxies for past conifer bark beetle outbreaks in Central Europe, as they occur together with fossils of I. typographus but appear to be well-preserved. A significant correlation was found between primary bark beetles and macroscopic charcoal densities in the sediment, highlighting the complex interactions between disturbance agents, bark beetles and fire, in this long-term regime of natural disturbances. Our 1400-year disturbance record shows how bark beetle outbreaks have been an important component of the regional natural disturbance regime for over a millennium and have intensified with increasing anthropogenic activity. Bark beetle outbreaks are likely one of the drivers promoting the future ecological stability of the temperate conifer ecosystem over decades to centuries