Serological and Genetic Evidence for Altered Complement System Functionality in Systemic Lupus Erythematosus: Findings of the GAPAID Consortium

Systemic lupus erythematosus is a chronic autoimmune disease with multifactorial ethiopathogenesis. The complement system is involved in both the early and late stages of disease development and organ damage. To better understand autoantibody mediated complement consumption we examined ex vivo immune complex formation on autoantigen arrays. We recruited patients with SLE (n = 211), with other systemic autoimmune diseases (n = 65) and non-autoimmune control subjects (n = 149). Standard clinical and laboratory data were collected and serum complement levels were determined. The genotype of SNP rs1143679 in the ITGAM gene was also determined. Ex vivo formation of immune complexes, with respect to IgM, IgG, complement C4 and C3 binding, was examined using a functional immunoassay on autoantigen microarray comprising nucleic acids, proteins and lipids. Complement consumption of nucleic acids increased upon binding of IgM and IgG even when serum complement levels were decreased due to consumption in SLE patients. A negative correlation between serum complement levels and ex vivo complement deposition on nucleic acid autoantigens is demonstrated. On the contrary, complement deposition on tested protein and lipid autoantigens showed positive correlation with C4 levels. Genetic analysis revealed that the non-synonymous variant rs1143679 in complement receptor type 3 is associated with an increased production of anti-dsDNA IgG antibodies. Notwithstanding, homozygous carriers of the previously reported susceptible allele (AA) had lower levels of dsDNA specific IgM among SLE patients. Both the non-synonymous variant rs1143679 and the high ratio of nucleic acid specific IgG/IgM were associated with multiple organ involvement. In summary, secondary complement deficiency in SLE does not impair opsonization of nucleic-acid-containing autoantigens but does affect other antigens and potentially other complement dependent processes. Dysfunction of the receptor recognizing complement opsonized immune complexes promotes the development of class-switched autoantibodies targeting nucleic acids.

Snail heterogeneity in clear cell renal cell carcinoma

Background: Intratumor heterogeneity may be responsible of the unpredictable aggressive clinical behavior that some clear cell renal cell carcinomas display. This clinical uncertainty may be caused by insufficient sampling, leaving out of histological analysis foci of high grade tumor areas. Although molecular approaches are providing important information on renal intratumor heterogeneity, a focus on this topic from the practicing pathologist' perspective is still pending. Methods: Four distant tumor areas of 40 organ-confined clear cell renal cell carcinomas were selected for histopathological and immunohistochemical evaluation. Tumor size, cell type (clear/granular), Fuhrman's grade, Staging, as well as immunostaining with Snail, ZEB1, Twist, Vimentin, E-cadherin, beta-catenin, PTEN, p-Akt, p110 alpha, and SETD2, were analyzed for intratumor heterogeneity using a classification and regression tree algorithm. Results: Cell type and Fuhrman's grade were heterogeneous in 12.5 and 60 % of the tumors, respectively. If cell type was homogeneous (clear cell) then the tumors were low-grade in 88.57 % of cases. Immunostaining heterogeneity was significant in the series and oscillated between 15 % for p110a and 80 % for Snail. When Snail immunostaining was homogeneous the tumor was histologically homogeneous in 100 % of cases. If Snail was heterogeneous, the tumor was heterogeneous in 75 % of the cases. Average tumor diameter was 4.3 cm. Tumors larger than 3.7 cm were heterogeneous for Vimentin immunostaining in 72.5 % of cases. Tumors displaying negative immunostaining for both ZEB1 and Twist were low grade in 100 % of the cases. Conclusions: Intratumor heterogeneity is a common event in clear cell renal cell carcinoma, which can be monitored by immunohistochemistry in routine practice. Snail seems to be particularly useful in the identification of intratumor heterogeneity. The suitability of current sampling protocols in renal cancer is discussed.

Genetic improvement of the herbivorous blunt snout bream (Megalobrama amblycephala)

Selection experiments with the herbivorous blunt snout bream or Wuchang bream (Megalobrama amblycephala) were started in 1985. Mass selection for size and length/depth ratio resulted in a significant increase in growth and better shape, while inbreeding led to a significant decrease in growth. The total selection ratio from fry to mature brooders was about 0.03 per cent per generation. In the grow out stage, the average daily body weight gains of two lines of fifth generation (F5) fish were 29 per cent and 20 per cent respectively more than the control group, with an average of 5.8 per cent and 4 per cent improvements per generation, respectively. The body was 4 per cent deeper in ratio of standard length/body depth. The effects of inbreeding were examined by crossing full-sibs, the offspring of which were kept without selection. The third generation inbred fish showed 17 per cent lower growth as compared to the control group, with an average of 7.5 per cent per generation. The results demonstrate that selection is a powerful tool to improve the economic traits of the blunt snout bream, but inbreeding can rapidly lead to a reduction in performance. In 2000, the 6th generation of selected bream was certified by the Chinese Ministry of Agriculture as a good breed for aquaculture.

Genetic diversity and selective breeding of red common carps in China

China has a very rich genetic diversity in common carp (Cyprinus carpio) and the red common carp plays an important role in Chinese aquaculture and genetic studies. Selective breeding, particularly crossbreeding has been applied successfully to red common carps in China, and the products of these efforts have been in commercial use since the 1970s. However, knowledge of the quantitative and molecular genetics of these carps is limited. Studies were therefore undertaken to: (1) understand the genetic diversity and genetic relationship of red common carps in China; (2) understand the inheritance of color phenotype of Oujiang color carp; (3) select stable Oujiang color carp with fast growth rate and ornamental Oujiang color carp comparable with the Koi common carp from Japan; (4) study the culture performance and culture systems suitable for the Oujiang color carp in cages and paddies; (5) extend better quality fish and appropriate culture systems for small scale fish farmers in poor areas.

Genetic diversity in wild stocks of the giant freshwater prawn (Macrobrachium rosenbergii): implications for aquaculture and conservation

The giant freshwater prawn (Macrobrachium rosenbergii) is cultured widely around the world but little is known about the levels and patterns of genetic diversity in either wild or cultured stocks. Studies have suggested that genetic diversity may be relatively low in some cultured stocks due to the history of how they were founded and subsequent exposure to repeated population bottlenecks in hatcheries. In contrast, wild stocks have an extensive distribution that extends from Southern Asia across Southeast (SE) Asia to the Pacific region. Therefore, wild stocks could be an important resource for genetic improvement of culture stocks in the future. Understanding the extent and patterns of genetic diversity in wild giant freshwater prawn stocks will assist decisions about the direction future breeding programs may take. Wild stock genetic diversity was examined using a 472 base-pair segment of the 16S rRNA gene in 18 wild populations collected from across the natural range of the species. Two major clades ("eastern" and "western") were identifi ed either side of Huxley’s line, with a minimum divergence of 6.2 per cent, which implies separation since the Miocene period (5-10 MYA). While divergence estimates within major clades was small (maximum 0.9 per cent), evidence was also found for population structuring at a lower spatial scale. This will be examined more intensively with a faster evolving mtDNA gene in the future.

Baseline biochemical and genetic profiles of four fishes from the River Nile

Six enzyme systems coding for 10 loci and 6 proteins were examined in the blood of Polypterus senegalus, Clarias lazera, Tilapia nilotica and Protopterus annectens, using electrophoresis. Six loci were polymorphic in all the four species, three polymorphic in three species and one polymorphic in T. nilotica. Four protein loci were monomorphic in all the four species with variants in P. senegalus and T. nilotica. Haemoglobin can be used as a species-specific marker. Polymorphism was 53-56 per cent and average heterozygosity was 0.1-0.15.

Marine fisheries, genetic effects and biodiversity

Preservation of marine biodiversity deserves serious consideration as almost 65% of the earth's organisms (excluding insects) are marine. There is little knowledge at present on the status of marine biodiversity. However, the seas are an important source of protein for human consumption and genetic diversity is a key factor in ecosystem functioning, stability and resilience. Overfishing and destructive practices may have unalterable impact on marine biodiversity. This paper discusses measures that can be adopted to protect the most productive areas of the marine ecosystem.