Association of KIR2DS1 and KIR2DS3 with fatal outcome in Ebola virus infection

Zaïre ebolavirus (ZEBOV) infection rapidly outruns the host's immunity and leads to death within a week. Fatal cases have been associated with an aberrant innate, proinflammatory immune response followed by a suppressed adaptive response leading to the rapid depletion of peripheral NK cells and lymphocytes. A critical role for NK cells has been suggested but not elucidated. In this genetic study, we investigated the association of KIR genotype with disease outcome by comparing genotypes of a Gabonese control population, IgG+ contacts, survivors, and fatalities of ZEBOV infection. We showed that the activating KIR2DS1 and KIR2DS3 genes associate with fatal outcome in Ebola virus infection. In addition, this study brings supplemental evidence in favor of the specificity of the IgG+ contact population. The outcome of fulminating Ebola virus infection could depend in part on the host's inherited KIR gene repertoire. This supports a key role for KIRs in disease susceptibility to infections

Activating KIR and HLA Bw4 Ligands Are Associated to Decreased Susceptibility to Pemphigus Foliaceus, an Autoimmune Blistering Skin Disease

The KIR genes and their HLA class I ligands have thus far not been investigated in pemphigus foliaceus (PF) and related autoimmune diseases, such as pemphigus vulgaris. We genotyped 233 patients and 204 controls for KIR by PCR-SSP. HLA typing was performed by LABType SSO reagent kits. We estimated the odds ratio, 95% confidence interval and performed logistic regression analyses to test the hypothesis that KIR genes and their known ligands influence susceptibility to PF. We found significant negative association between activating genes and PF. The activating KIR genes may have an overlapping effect in the PF susceptibility and the presence of more than three activating genes was protective (OR = 0.49, p = 0.003). A strong protective association was found for higher ratios activating/inhibitory KIR (OR = 0.44, p = 0.001). KIR3DS1 and HLA-Bw4 were negatively associated to PF either isolated or combined, but higher significance was found for the presence of both together (OR = 0.34, p<10−3) suggesting that the activating function is the major factor to interfere in the PF pathogenesis. HLA-Bw4 (80I and 80T) was decreased in patients. There is evidence that HLA-Bw4(80T) may also be important as KIR3DS1 ligand, being the association of this pair (OR = 0.07, p = 0.001) stronger than KIR3DS1-Bw4(80I) (OR = 0.31, p = 0.002). Higher levels of activating KIR signals appeared protective to PF. The activating KIR genes have been commonly reported to increase the risk for autoimmunity, but particularities of endemic PF, like the well documented influence the environmental exposure in the pathogenesis of this disease, may be the reason why activated NK cells probably protect against pemphigus foliaceus

Psoriasis Patients Are Enriched for Genetic Variants That Protect against HIV-1 Disease

An important paradigm in evolutionary genetics is that of a delicate balance between genetic variants that favorably boost host control of infection but which may unfavorably increase susceptibility to autoimmune disease. Here, we investigated whether patients with psoriasis, a common immune-mediated disease of the skin, are enriched for genetic variants that limit the ability of HIV-1 virus to replicate after infection. We analyzed the HLA class I and class II alleles of 1,727 Caucasian psoriasis cases and 3,581 controls and found that psoriasis patients are significantly more likely than controls to have gene variants that are protective against HIV-1 disease. This includes several HLA class I alleles associated with HIV-1 control; amino acid residues at HLA-B positions 67, 70, and 97 that mediate HIV-1 peptide binding; and the deletion polymorphism rs67384697 associated with high surface expression of HLA-C. We also found that the compound genotype KIR3DS1 plus HLA-B Bw4-80I, which respectively encode a natural killer cell activating receptor and its putative ligand, significantly increased psoriasis susceptibility. This compound genotype has also been associated with delay of progression to AIDS. Together, our results suggest that genetic variants that contribute to anti-viral immunity may predispose to the development of psoriasis

Different Patterns of Evolution in the Centromeric and Telomeric Regions of Group A and B Haplotypes of the Human Killer Cell Ig-Like Receptor Locus

The fast evolving human KIR gene family encodes variable lymphocyte receptors specific for polymorphic HLA class I determinants. Nucleotide sequences for 24 representative human KIR haplotypes were determined. With three previously defined haplotypes, this gave a set of 12 group A and 15 group B haplotypes for assessment of KIR variation. The seven gene-content haplotypes are all combinations of four centromeric and two telomeric motifs. 2DL5, 2DS5 and 2DS3 can be present in centromeric and telomeric locations. With one exception, haplotypes having identical gene content differed in their combinations of KIR alleles. Sequence diversity varied between haplotype groups and between centromeric and telomeric halves of the KIR locus. The most variable A haplotype genes are in the telomeric half, whereas the most variable genes characterizing B haplotypes are in the centromeric half. Of the highly polymorphic genes, only the 3DL3 framework gene exhibits a similar diversity when carried by A and B haplotypes. Phylogenetic analysis and divergence time estimates, point to the centromeric gene-content motifs that distinguish A and B haplotypes having emerged ∼6 million years ago, contemporaneously with the separation of human and chimpanzee ancestors. In contrast, the telomeric motifs that distinguish A and B haplotypes emerged more recently, ∼1.7 million years ago, before the emergence of Homo sapiens. Thus the centromeric and telomeric motifs that typify A and B haplotypes have likely been present throughout human evolution. The results suggest the common ancestor of A and B haplotypes combined a B-like centromeric region with an A-like telomeric region

Pokazatel'nyjj metod ocenki kachestva silosov

In 428 samples of silage the pH value was determined with the use of test paper and a pH - meter N-517. The level of NH₃ was determined with Conway method and with the indicatory method. The level of sugar uas determined with Glucotest and the content of acids (lactic, acetic, butyric) with Lepper method. Qn the baeie of the results statistic correlations were calculated and that allowed to work out a new method of silage quality evaluation. This method is based on the use of indicatory methods to indicate pH, NH₃ and sugar. The achieved data get points and the score is the base of classifying the silage to a proper class.В 428 образцах силосов определили величину рН применяя реактивную бумажку и рН-метр N-517. Уровень аммиака определили методом Конвея и показательным методом. Уровень сахара определили применяя глюкотекст а также содержание кислот (масляной, уксусной, молочной) по методу Леппера. На основе полученных результатов определили статистические взаимозависимости, которые позволили разработать новую оценку качества силоса. Оценка эта опирается на применению показательных методов для определения рН, аммиака и сахара, полученные величины получают балльную характеристику и их сумма является основой для отнесения силоса к определенному классу

Comparison of cadmium, zinc, manganese and nickel concentrations in fillets of selected species of food fish

Celem pracy było porównanie koncentracji kadmu, cynku, manganu i niklu w filetach popularnych gatunków ryb konsumpcyjnych dostępnych na rynku polskim: sprowadzanych z hodowli prowadzonych w Azji – tilapii nilowej i pangi, jednego z gatunków ryb morskich – dziko żyjącego mintaja, oraz pochodzącego z rodzimej hodowli pstrąga tęczowego. Uzyskane wyniki wskazują, że najwyższe poziomy kadmu występują w mięśniach pangi i tilapii nilowej. Najwyższe poziomy cynku, manganu i niklu obserwowano w tkance mięśniowej mintaja, co potwierdza pogląd, że ryby morskie są cennym źródłem mikroelementów w diecie człowieka. Jednak najkorzystniejsze proporcje koncentracji badanych metali odnotowano u pstrąga, gdzie wykazano najniższe poziomy kadmu i niklu – metali należących do szczególnie szkodliwych dla środowiska wodnego, a jednocześnie istotnie wyższe niż u pangi i tilapii poziomy cynku i manganu. Uzyskane wyniki pozwalają stwierdzić, że spośród badanych gatunków pstrąg potokowy jest najbezpieczniejszym dla konsumenta źródłem mikroelementów.The aim of the study was to compare the concentration of cadmium, zinc, manganese and nickel in fillets of four popular fish species available on the Polish market: Nile tilapia and pangasius imported from fish farms in Asia; pollock, a marine fish species living in the wild; and rainbow trout farmed domestically. The highest cadmium levels were found in the muscles of pangasius and Nile tilapia. The highest levels of zinc, manganese and nickel were observed in the muscle tissue of pollock, which supports the view that marine fish are a valuable source of micronutrients in the human diet. However, the best ratio of concentrations of the metals analysed was noted in trout, which had the lowest levels of cadmium and nickel, which are particularly harmful to the aquatic environment, and significantly higher levels of zinc and manganese than in pangasius and tilapia. The results obtained in the study indicate that trout is the safest source of micronutrients for the consumer