Genetic susceptibility to chronic Chagas disease: an overview of single nucleotide polymorphisms of cytokine genes

Chagas disease is a parasitic infection that is a significant public health problem in Latin America. The mechanisms responsible for susceptibility to the infection and the mechanisms involved in the development of cardiac and digestive forms of chronic Chagas disease remain poorly understood. However, there is growing evidence that differences in susceptibility in endemic areas may be attributable to host genetic factors. The aim of this overview was to analyze the genetic susceptibility to human Chagas disease, particularly that of single nucleotide polymorphisms of cytokine genes. A review of the literature was conducted on the following databases: PubMed/MEDLINE and Scopus. The search strategy included using the following terms: "Cytokines", "Single Nucleotide Polymorphisms" and "Chagas Disease". After screening 25 citations from the databases, 19 studies were selected for the overview. A critical analysis of the data presented in the articles suggests that genetic susceptibility to Chagas disease and chronic Chagas cardiomyopathy is highly influenced by the complexity of the immune response of the host. Follow-up studies based on other populations where Chagas disease is endemic (with distinct ethnic and genetic backgrounds) need to be conducted. These should use a large sample population so as to establish what cytokine genes are involved in susceptibility to and/or progression of the disease.     

Functional Feeds Reduce Heart Inflammation and Pathology in Atlantic Salmon (Salmo salar L.) following Experimental Challenge with Atlantic Salmon Reovirus (ASRV)

Heart and Skeletal Muscle Inflammation (HSMI), recently associated with a novel Atlantic salmon reovirus (ASRV), is currently one of the most prevalent inflammatory diseases in commercial Atlantic salmon farms in Norway. Mortality varies from low to 20%, but morbidity can be very high, reducing growth performance and causing considerable financial impact. Clinical symptoms, including myocarditis, myocardial and red skeletal muscle necrosis, correlate with the intensity of the inflammatory response. In the present study, the effects of two functional feeds (FF1 and FF2) were compared to a standard commercial reference feed (ST) in Atlantic salmon subjected to an ASRV challenge. The functional feeds had reduced levels of total lipid and digestible energy, and different levels and proportions of long-chain polyunsaturated fatty acids (LC-PUFA). The objective was to determine whether these feeds could provide effective protection by decreasing the inflammatory response associated with HSMI. Histopathology, viral load, fatty acid composition and gene expression of heart tissue were assessed over a period of 16 weeks post-infection with ASRV. The viral load and histopathology scores in heart tissue in response to ASRV infection were reduced in fish fed both functional feeds, with FF1 showing the greatest effect. Microarray hierarchical cluster analysis showed that the functional feeds greatly affected expression of inflammation/immune related genes over the course of the ASRV infection. Viral load correlated with up-regulation of pro-inflammatory genes at the early-mid stages of infection in fish fed the ST diet. Expression of inflammatory genes 16-weeks after ASRV challenge reflected the difference in efficacy between the functional feeds, with fish fed FF1 showing lower expression. Thus, severity of the lesions in heart tissue correlated with the intensity of the innate immune response and was associated with tissue fatty acid compositions. The present study demonstrated that dietary modulation through clinical nutrition had major influences on the development and severity of the response to ASRV infection in salmon. Thus, HSMI was reduced in fish fed the functional feeds, particularly FF1. The modulation of gene expression between fish fed the different feeds provided further insight into the molecular mechanisms and progression of the inflammatory and immune responses to ASRV infection in salmon.     

HrpM is involved in glucan biosynthesis,biofilm formation and pathogenicity in Xanthomonas citri ssp. citri

Xanthomonas citri ssp. citri (Xcc) is the causal agent of citrus canker. This bacterium develops a characteristic biofilm on both biotic and abiotic surfaces. A biofilm‐deficient mutant was identified in a screening of a transposon mutagenesis library of the Xcc 306 strain constructed using the commercial Tn5 transposon EZ‐Tn5 <KAN‐2> Tnp Transposome (Epicentre). Sequence analysis of a mutant obtained in the screening revealed that a single copy of the EZ‐Tn5 was inserted at position 446 of hrpM, a gene encoding a putative enzyme involved in glucan synthesis. We demonstrate for the first time that the product encoded by the hrpM gene is involved in β‐1,2‐glucan synthesis in Xcc. A mutation in hrpM resulted in no disease symptoms after 4 weeks of inoculation in lemon and grapefruit plants. The mutant also showed reduced ability to swim in soft agar and decreased resistance to H ₂ O ₂ in comparison with the wild‐type strain. All defective phenotypes were restored to wild‐type levels by complementation with the plasmid pBBR1‐MCS containing an intact copy of the hrpM gene and its promoter. These results indicate that the hrpM gene contributes to Xcc growth and adaptation in its host plant.     

New cytogenetic aberrations found in a case of aggressive retinoblastoma

We describe a case of retinoblastoma with an atypical presentation and previously unreported cytogenetic aberrations. A 19-month-old girl with left intraocular retinoblastoma was treated with enucleation and chemotherapy. The disease showed aggressive evolution within a short period between diagnosis and relapse. Eight months after diagnosis, a new large tumor was present in the orbit of the right eye, with diffuse bone pain, pancytopenia and diffuse infiltration into the bone marrow and the central nervous system. The child did not respond to treatment and died. Cytogenetic studies made with G-banding, FISH and SKY analysis showed chromosomal aberrations commonly associated with retinoblastoma, including del(13q), i(6p), +1, and monosomy 16, along with others that had not been reported previously, including dup(5q), dic(15;22) and add(14q). The new chromosomal aberrations may be related to the aggressiveness of the disease in this case.     

Cellular localization of Nicastrin affects amyloid beta species production

The gamma-secretase complex, composed by presenilin, nicastrin, APH-1 and PEN-2, is involved in intramembranous proteolysis of membrane proteins, such as amyloid precursor protein or Notch. Cleavage occurs in multiple cellular compartments. Here, nicastrin mutants containing targeting signals to the endoplasmic reticulum, trans-Golgi network, lysosomes, or plasma membrane have been shown to yield active gamma-secretase complexes with different activities and specificities: wild-type and plasma membrane nicastrin complexes yielded the highest amounts of secreted amyloid-beta peptide (Abeta), predominantly Abeta40, whereas intracellular targeted mutants produced intracellular Abeta, with a comparatively higher amount of Abeta42. These results suggest that compartmental microenvironments play a role in gamma-secretase activity and specificity.     

Laurus novocanariensis essential oil: Seasonal variation and valorization

We investigated the qualitative and quantitative seasonal variation of the leaf and fruit oils of the Macaronesian endemism Laurus novocanariensis and their plant defensive potential. The monoterpene fraction dominated the leaf (74%) and berry essential oils (73–44%, ripe–unripe). The insect antifeedant effects of these oils were species- and season-dependent against the aphids (Myzus persicae and Rhopalosiphum padi). Overall, the biological effects of these oils correlated with the oxygenated terpene fraction. Among the pure components tested, β-caryophyllene and its oxide were strong antifeedants to Leptinotarsa decemlineata and Spodoptera littoralis. The aphids responded to β-ocimene, β-pinene, 1,8-cineole, linalool (antifeedants) and linalool oxide (attractive to M. persicae). The antifungal effects of the leaf oils on Fusarium spp. were season-dependent. β-Caryophyllene oxide proved to be a strong antifungal. L. novocanariensis oils inhibited Lactuca sativa germination and radicle elongation, the leaves being more effective. Linalool also inhibited seed germination.     

Assessment methodology for southern siliceous basins in Portugal

A sampling programme was developed in three stream types, of siliceous geology, from the south of Portugal (small and mid-sized lowland streams and small-sized median altitude streams). The samples were taken according to the AQEM site protocol procedure, keeping transport and depositional habitats samples separated. In each stream type, at least 13 sites were studied over a gradient of organic pollution (pre-classification). The benthic macroinvertebrates were identified to the lowest possible taxonomic level. A Detrended Correspondence Analysis of macroinvertebrate communities identified a gradient of organic pollution strongly related to the first axis. This ordination allowed the establishment of classes of organic pollution using the Kmeans software (post-classification). Metrics based on the macroinvertebrate communities (tolerance, richness, composition and trophic structure) were computed and tested for correlation with the gradient of organic pollution (first axis of DCA). Most of the selected metrics were able to discriminate the four quality classes (high, good, moderate and poor) of ecological status. A multimetric index, integrating ASPT′ index, Trichoptera families and percentage of Gasteropoda, Oligochaeta and Diptera, is proposed to assess the ecological status of Portuguese southern siliceous basins.     

Gonad development and fatty acid composition of Patella depressa Pennant (Gastropoda: Prosobranchia) populations with different patterns of spatial distribution, in exposed and sheltered sites

The present study examines the effect of shore exposure on the feeding performance (assessed by fatty acid analyses of the whole body) and gonad condition (stage of development and gonad somatic index, GSI) of Patella depressa populations. Male and female limpets were collected at exposed and sheltered sites, during winter and summer. The population at the exposed site was at a more advanced stage of gonad development, with a higher dispersion of gonad stages, both in winter and summer. Additionally, limpets from the exposed site, particularly the males, presented a higher GSI than the corresponding stage in the sheltered site. The quantitatively most important fatty acids were the saturated fatty acids (SFA) 16:0, 14:0, and 18:0, the monounsaturated fatty acids (MUFA) 18:1(n−7), 18:1(n−9), 16:1(n−7) and 20:1(n−9) and the polyunsaturated fatty acids (PUFA) 20:5(n−3) and 20:4(n−6). Females had a significantly higher fatty acid methyl esters (FAME) content (in summer and winter) and higher amounts of SFA and MUFA (in summer), which points to a higher degree of storage of neutral lipids in this sex. Male and female limpets at the exposed site had a significantly higher FAME, SFA, MUFA, PUFA and highly unsaturated fatty acids (HUFA) content than the corresponding sex in the sheltered site in summer. In addition, an inversion in the eicosapentaenoic acid (EPA)/arachidonic acid (ARA) and (n−3)/(n−6) ratios was observed in the sheltered site, as a result of the significantly higher levels of ARA and (n−6) fatty acids and lower amounts of EPA and (n−3) fatty acids found in the sheltered limpets. A high variability among patches in the fatty acid composition in the exposed site was found in winter, possibly related to the aggregation of limpets at this time. The differences found between limpets from the exposed and sheltered sites suggest qualitative and quantitative differences in their diets. Additionally, the results show that the spatial aggregation strategy adopted by limpets in sites of great wave and wind exposure does not affect their feeding and reproductive success, at least in the site examined here. In fact, more developed gonads, a higher GSI and an elevated FAME content was found in the exposed population. Possible factors are suggested and discussed to explain these observations.