Maintenance of Chronic Fatigue Syndrome (CFS) in Young CFS Patients Is Associated with the 5-HTTLPR and SNP rs25531 A > G Genotype

Earlier studies have shown that genetic variability in the SLC6A4 gene encoding the serotonin transporter (5-HTT) may be important for the re-uptake of serotonin (5-HT) in the central nervous system. In the present study we investigated how the 5-HTT genotype i.e. the short (S) versus long (L) 5-HTTLPR allele and the SNP rs25531 A > G affect the physical and psychosocial functioning in patients with chronic fatigue syndrome (CFS). All 120 patients were recruited from The Department of Paediatrics at Oslo University Hospital, Norway, a national referral center for young CFS patients (12–18 years). Main outcomes were number of steps per day obtained by an accelerometer and disability scored by the Functional Disability Inventory (FDI). Patients with the 5-HTT SS or SL_G genotype had a significantly lower number of steps per day than patients with the 5-HTT L_AL_G, SL_A or L_AL_A genotype. Patients with the 5-HTT SS or SL_G genotype also had a significantly higher FDI score than patients with the 5-HTT L_AL_G, SL_A or L_AL_A genotype. Thus, CFS patients with the 5-HTT SS or SL_G genotype had worse 30 weeks outcome than CFS patients with the 5-HTT L_AL_G, SL_A or L_AL_A genotype. The present study suggests that the 5-HTT genotype may be a factor that contributes to maintenance of CFS.     

The effect of different nutrient concentrations on the growth rate and nitrogen storage of watercress (Nasturtium officinale R. Br.)

The mechanisms that allow broadly distributed aquatic plants to inhabit variable resource environments are unclear, yet understanding these mechanisms is important because broad environmental tolerance is often linked to invasiveness in terrestrial and aquatic plants. In an experimental stream, we examined the effects of different nutrient concentrations on the growth rate, biomass, and foliar nutrient concentrations of a cosmopolitan and potentially invasive aquatic plant, Nasturtium officinale (R. Br.). Nasturtium seedlings were grown under six nutrient treatment levels ranging from 0.64 μm N:0.09 μm P to 1531 μm N:204.13 μm P, for 8 weeks. Absolute and relative growth rates, and biomass of seedlings increased along a gradient of increasing nutrient concentrations but the effect of nutrient concentration was dependent on growing time. Seedling biomass varied among nutrient treatments in weeks 4 through 8 of the experiment, but did not differ in week 2. By week 8, the two highest nutrient treatments had greater biomass than the two lowest nutrient treatments. Foliar nitrogen concentration increased, whereas carbon concentration and C:N ratios decreased in response to increasing nutrients. Nasturtium grows slowly in nutrient-poor conditions but rapidly increases its growth, biomass accrual, and nitrogen storage as conditions become nutrient-rich. The response of Nasturtium to enhanced nutrient conditions may indicate how aquatic nuisance species successfully invade and dominate plant communities in streams, where resources often vary both temporally and spatially.     

Fitness landscape of Atlantic cod shaped by harvest selection and natural selection

Harvesting may lead to evolutionary changes in life histories on a contemporary time scale, changes that could be maladaptive in natural contexts. However, our understanding of the strength and direction of harvest-induced selection versus natural selection is still limited, partly due to the difficulty of tracking the fate of individuals in the wild. Here, we present direct estimates of harvest mortality, natural mortality and site fidelity of coastal Atlantic cod (Gadus morhua) from the Norwegian Skagerrak coast. Furthermore, we present standardised selection differentials for fish body size. Estimates are obtained from acoustic telemetry, where we continuously monitored fish (n = 60) within a semi-sheltered area using a network of 25 listening stations. To obtain additional information about harvested cod, all fish (body size: 30–66 cm) were also tagged with traditional T-bar tags with a printed reward of 500 NOK (60 E). We estimate that 75% of the fish died within the study area during 1 year. Fishing mortality was markedly higher than natural mortality. Together, recreational fishers and commercial fishers caught at least 50% of the tagged fish during 1 year. Standardised selection differentials showed that fisheries targeted larger fish (i.e. favoured the survival of smaller fish), while natural selection favoured the survival of larger fish. Albeit on a small scale, we provide empirical evidence that harvesting can have a dominant influence on the fitness landscape experienced by a marine fish such as the Atlantic cod. We suggest that no-take marine reserves may help to counter evolutionary impacts of harvesting in the ocean.     

Boric Acid Inhibits Germination and Colonization of Saprolegnia Spores In Vitro and In Vivo

Saprolegnia infections cause severe economic losses among freshwater fish and their eggs. The banning of malachite green increased the demand for finding effective alternative treatments to control the disease. In the present study, we investigated the ability of boric acid to control saprolegniosis in salmon eggs and yolk sac fry. Under in vitro conditions, boric acid was able to decrease Saprolegnia spore activity and mycelial growth in all tested concentrations above 0.2 g/L, while complete inhibition of germination and growth was observed at a concentration of 0.8 g/L. In in vivo experiments using Atlantic salmon eyed eggs, saprolegniosis was controlled by boric acid at concentrations ranging from 0.2–1.4 g/L during continuous exposure, and at 1.0–4.0 g/L during intermittent exposure. The same effect was observed on salmon yolk sac fry exposed continuously to 0.5 g/L boric acid during the natural outbreak of saprolegniosis. During the experiments no negative impact with regard to hatchability and viability was observed in either eggs or fry, which indicate safety of use at all tested concentrations. The high hatchability and survival rates recorded following the in vivo testing suggest that boric acid is a candidate for prophylaxis and control of saprolegniosis.     

Mitochondrial Dysfunction Is Involved in the Toxic Activity of Boric Acid against Saprolegnia

There has been a significant increase in the incidence of Saprolegnia infections over the past decades, especially after the banning of malachite green. Very often these infections are associated with high economic losses in salmonid farms and hatcheries. The use of boric acid to control the disease has been investigated recently both under in vitro and in vivo conditions, however its possible mode of action against fish pathogenic Saprolegnia is not known. In this study, we have explored the transformation in Saprolegnia spores/hyphae after exposure to boric acid (1 g/L) over a period 4–24 h post treatment. Using transmission electron microscopy (TEM), early changes in Saprolegnia spores were detected. Mitochondrial degeneration was the most obvious sign observed following 4 h treatment in about 20% of randomly selected spores. We also investigated the effect of the treatment on nuclear division, mitochondrial activity and function using confocal laser scanning microscopy (CLSM). Fluorescence microscopy was also used to test the effect of treatment on mitochondrial membrane potential and formation of reactive oxygen species. Additionally, the viability and proliferation of treated spores that correlated to mitochondrial enzymatic activity were tested using an MTS assay. All obtained data pointed towards changes in the mitochondrial structure, membrane potential and enzymatic activity following treatment. We have found that boric acid has no effect on the integrity of membranes of Saprolegnia spores at concentrations tested. It is therefore likely that mitochondrial dysfunction is involved in the toxic activity of boric acid against Saprolegnia spp.     

Molecular resistance fingerprint of pemetrexed and platinum in a long-term survivor of mesothelioma

Background

Pemetrexed, a multi-folate inhibitor combined with a platinum compound is the first-line treatment of malignant mesothelioma, but median survival is still one year. Intrinsic and acquired resistance to pemetrexed is common, but its biological basis is obscure. Here we report for the first time a genome-wide profile of acquired resistance in the tumour from an exceptional case with advanced pleural mesothelioma and almost six years survival after 39 cycles of second-line pemetrexed/carboplatin treatment.

Methodology and Principal Findings

Genome-wide analysis with Illumina BeadChip Kit of 25,000 genes was performed on mRNA from pre-treatment and post-resistance biopsies from this individual as well on case and control samples from our previously published study (in total 17 samples). Cell specific expression of proteins encoded by selected genes were analysed by immunohistochemistry. Serial serum levels of CA125, CYFRA21-1 and SMRP levels were examined. TS protein, the main target of pemetrexed was overexpressed. Proteins and genes related to DNA damage response, elongation and telomere extension and repair related directly and indirectly to platinum resistance were overexpressed, as the CHK1 protein and the genes CHEK2, LIG3, POLD1, POLA2, FANCD2, PRPF19, RECQ5 respectively, the last two not previously described in mesothelioma. We observed a down-regulation of leukocyte transendothelial migration and cell adhesion molecules pathways. Silencing of NT5C in two mesothelioma cell lines did not sensitize the cells to Pemetrexed. Proposed resistance markers are TS, KRT7/ CK7, TYMP/ thymidine phosphorylase and down-regulated SPARCL1 and CDKN1B. Moreover, comparison of the primary expression of the sensitive versus a primary resistant case showed multi-fold overexpressed DNA repair, cell cycle, cytokinesis, and spindle formation in the latter. Serum CA125 and SMRP reflected the clinical and radiological course and tumour burden.

Conclusions

Genome-wide microarray of mesothelioma pre- and post-resistance biopsies indicated a novel resistance signature to pemetrexed/carboplatin that deserve validation in a larger cohort.     

The functional <Emphasis Type="Italic">SLC11A1</Emphasis> gene polymorphisms are associated with sarcoidosis in Turkish population

Sarcoidosis (SA) is an immune-mediated multisystemic disorder of unknown etiology characterized by the accumulation of lymphocytes, mononuclear phagocytes and epithelioid cell granulomas involved in different organs and tissues. The belief that genetics contribute to SA etiology is supported by twin studies, disease clustering in families and racial differences in incidence rates. Involvements of SLC11A1 in macrophage function and activation, makes it an attractive candidate gene for immune-mediated and infectious diseases. We investigated the association between SA and four polymorphisms of the SLC11A1 gene, including a single nucleotide change in intron 4 (INT4); a nonconservative single-base substitution at codon 543 (D543N); a TGTG deletion in the 3′ untranslated region; and the functional (GT)_n repeat polymorphism in the 5′ region, in 95 Turkish SA patients and 150 healthy controls, by using amplification refractory mutation system–polymerase chain reaction and sequencing. We found significant association between SA and INT4 G/C allele frequency (P = 0.0000; odds ratio 2.75; 95% confidence interval 1.68–4.52) and 5′(GT)_n allele 2/3 frequency (P = 0.0000; odds ratio 2.69; 95% confidence interval 1.61–4.47) suggesting that SLC11A1 might be a plausible candidate gene for SA.