The PNPLA3 Ile148Met interacts with overweight and dietary intakes on fasting triglyceride levels

The Ile148Met (rs738409, G-allele) in the patatin-like phospholipase domain-containing protein 3 gene (PNPLA3) associates with liver fat content and may lead to loss-of-function (hydrolysis) or gain-of-function (CoA-dependent lysophosphatidic acid acyltransferase) defects. PNPLA3 is up-regulated by dietary carbohydrates, and interactions between rs738409 and carbohydrates, and sugar and ω6:ω3-polyunsaturated fatty acid (PUFA) ratio on hepatic fat accumulation have been reported. We examined interaction between rs738409 and overweight, and between rs738409 and dietary intakes (carbohydrates, sucrose and ω6:ω3-PUFA ratio), on fasting triglyceride levels. From the Malmo Diet and Cancer Study-Cardiovascular Cohort, 4,827 individuals without diabetes aged 58 ± 6 years, 2,346 with BMI ≤ 25 kg/m² and 2,478 with BMI > 25 kg/m², were included in cross-sectional analyses. Dietary data were collected by a modified diet history method. Overweight modified the association between rs738409 and fasting triglyceride levels (P_interaction = 0.003). G-allele associated with lower triglycerides only among overweight individuals (P = 0.01). Nominally, significant interaction on triglyceride levels was observed between rs738409 and sucrose among normal-weight individuals (P_interaction = 0.03). G-allele associated with lower triglycerides among overweight individuals in the lowest tertiles of carbohydrate and ω6:ω3-PUFA ratio (P = 0.04 and P = 0.001) and with higher triglycerides among normal-weight individuals in the highest tertile of sucrose (P = 0.001). We conclude that overweight and dietary sucrose may modify the association between rs738409 and fasting triglyceride levels.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-014-0388-4) contains supplementary material, which is available to authorized users.     

Occurrence of neurotrophin receptors and transmitters in the developing Xenopus gut

The ontogeny of gut innervation in the anuran amphibian Xenopus laevis was studied using immunohistochemistry on sections of whole larvae from NF stages 38-52. Immunoreactivity to acetylated tubulin confirmed the presence of nerve fibres as early as stages 38-39. Actin immunoreactivity was found at stage 41, indicating the presence of smooth muscle cells. Trk-like neurotrophin receptors were occasionally found in nerve fibres as soon as stages 38-39. Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) immunoreactivities coexisted in nerves innervating the gut wall from stages 40-41, and nitric oxide synthase (NOS) from stage 42. Substance P/neurokinin A (SP/NKA) occurred at stage 42. In all these cases, the first fibres were observed in the oesophagus. Calcitonin gene-related peptide (CGRP) was first observed in nerves at stage 48. In general, VIP/PACAP and NOS innervation was denser than the tachykinin innervation. In conclusion, the development of nerve fibres in the Xenopus gut is probably dependent on neurotrophins that may act via Trk-like receptors and occur before the gut wall is fully organised morphologically. Feeding in Xenopus larvae starts at NF stage 45. The study demonstrates that several of the transmitters investigated are expressed in the gut innervation (and in endocrine cells) prior to this stage.     

Misreading of termination codons in eukaryotes by natural nonsense suppressor tRNAs

Translational stop codon readthrough provides a regulatory mechanism of gene expression that is extensively utilised by positive-sense ssRNA viruses. The misreading of termination codons is achieved by a variety of naturally occurring suppressor tRNAs whose structure and function is the subject of this survey. All of the nonsense suppressors characterised to date (with the exception of selenocysteine tRNA) are normal cellular tRNAs that are primarily needed for reading their cognate sense codons. As a consequence, recognition of stop codons by natural suppressor tRNAs necessitates unconventional base pairings in anticodon–codon interactions. A number of intrinsic features of the suppressor tRNA contributes to the ability to read non-cognate codons. Apart from anticodon–codon affinity, the extent of base modifications within or 3′ of the anticodon may up- or down-regulate the efficiency of suppression. In order to out-compete the polypeptide chain release factor an absolute prerequisite for the action of natural suppressor tRNAs is a suitable nucleotide context, preferentially at the 3′ side of the suppressed stop codon. Three major types of viral readthrough sites, based on similar sequences neighbouring the leaky stop codon, can be defined. It is discussed that not only RNA viruses, but also the eukaryotic host organism might gain some profit from cellular suppressor tRNAs.     

Sexual signaling in the European bitterling: females learn the truth by direct inspection of the resource

In many taxa females appear to base their mate choice on multipletraits. But the relative importance of different traits inmate choice has rarely been determined. Here we show that femalesof a freshwater fish, the European bitterling, Rhodeus sericeus,base their mate choice on multiple traits that differ in theirreliability as indicators of expected reproductive successand are used at different stages of the decision process. Theinitial decision to inspect a male is based on male behaviorand red coloration, whereas the final spawning decision isbased on the quality of the live unionid mussel, Anodonta anatina,that the male is defending as an oviposition site. Male traitsmay indicate which males are worth inspecting by reflectingmale quality, such as reproductive condition and genetic constitution.Male traits do not, however, reflect mussel quality, as bright males also court females vigorously toward mussels that yielda low probability of survival of the offspring. Females, onthe other hand, are choosier than males in their choice ofspawning site and seem to gain reliable information about thesurvival probability of the eggs by inspecting the mussel directly.     

Establishing Causality between Pollution and Effects at Different Levels of Biological Organization: The VALIMAR Project

The study summarizes the objectives of the VALIMAR project and gives selected examples of biomarker responses that allow causal relationships to be established between exposure and biological effects at different levels of biological organization. In this project, active and passive biomonitoring experiments with brown trout (Salmo trutta f. fario) and stone loach (Barbatula barbatula) were performed in two small streams in southern Germany between 1995 and 1999 in parallel with investigations on contaminant mixtures in the laboratory in order to evaluate the suitability of biomarkers representing different levels of biological organization for the assessment of pollution in small streams. In addition to biomarker studies, the morphology of the test streams was characterized and limnological and chemical parameters were monitored. Early life stage tests and ecological studies of brown trout and stone loach population demography, of the fish assemblages, and the macro- and meiozoobenthos communities in the two test streams were included in the project. Several causality criteria were addressed by means of combined (1) laboratory and field studies, (2) chemical, biological, and statistical investigations, and (3) in vivo and in vitro studies that allowed establishment of cause-effect relationships at different biological levels. The comparison of results obtained at these levels allowed identification of mechanisms responsible for the respective effects (coherence of association, biological plausibility). Finally, individual responses (biomarkers, bioindicators) could be extrapolated to higher biological levels (population, community) thus addressing the criteria of ‘time order’ and ‘coherence of association’.     

Assessment of Metabolomic and Proteomic Biomarkers in Detection and Prognosis of Progression of Renal Function in Chronic Kidney Disease

Chronic kidney disease (CKD) is part of a number of systemic and renal diseases and may reach epidemic proportions over the next decade. Efforts have been made to improve diagnosis and management of CKD. We hypothesised that combining metabolomic and proteomic approaches could generate a more systemic and complete view of the disease mechanisms. To test this approach, we examined samples from a cohort of 49 patients representing different stages of CKD. Urine samples were analysed for proteomic changes using capillary electrophoresis-mass spectrometry and urine and plasma samples for metabolomic changes using different mass spectrometry-based techniques. The training set included 20 CKD patients selected according to their estimated glomerular filtration rate (eGFR) at mild (59.9±16.5 mL/min/1.73 m²; n = 10) or advanced (8.9±4.5 mL/min/1.73 m²; n = 10) CKD and the remaining 29 patients left for the test set. We identified a panel of 76 statistically significant metabolites and peptides that correlated with CKD in the training set. We combined these biomarkers in different classifiers and then performed correlation analyses with eGFR at baseline and follow-up after 2.8±0.8 years in the test set. A solely plasma metabolite biomarker-based classifier significantly correlated with the loss of kidney function in the test set at baseline and follow-up (ρ = −0.8031; p<0.0001 and ρ = −0.6009; p = 0.0019, respectively). Similarly, a urinary metabolite biomarker-based classifier did reveal significant association to kidney function (ρ = −0.6557; p = 0.0001 and ρ = −0.6574; p = 0.0005). A classifier utilising 46 identified urinary peptide biomarkers performed statistically equivalent to the urinary and plasma metabolite classifier (ρ = −0.7752; p<0.0001 and ρ = −0.8400; p<0.0001). The combination of both urinary proteomic and urinary and plasma metabolic biomarkers did not improve the correlation with eGFR. In conclusion, we found excellent association of plasma and urinary metabolites and urinary peptides with kidney function, and disease progression, but no added value in combining the different biomarkers data.     

Predator–prey interactions between Dugesia gonocephala and free-living nematodes

1. Three groups of laboratory experiments clarified the role of nematodes as a potential food resource for the triclad Dugesia gonocephala. The first group measured the functional response of adult D. gonocephala feeding on juvenile or adult Caenorhabditis elegans. The feeding rates of D. gonocephala on adult and juvenile C. elegans followed a type II functional response. The maximum number of adult nematodes and juvenile nematodes eaten by a single D. gonocephala individual within 3 h was 94 and 197 nematodes, respectively. 2. A second group of microcosm experiments investigated the effect of D. gonocephala on the density and the vertical distribution of a nematode community in fine sand. The following treatments were performed: (i) microcosms with 400 nematodes and (ii) microcosms with 400 nematodes and one D. gonocephala. After 5 days, nematodes as a group, as well as the dominant species Tobrilus pellucidus and Trischistoma monohystera, showed no significant difference in vertical patterns between the treatments with and without D. gonocephala. 3. The third group of experiments determined whether grain size of the sediment (sand, fine gravel and coarse gravel) altered the ability of D. gonocephala to consume adult C. elegans. Sand and fine gravel reduced the predation effectiveness of D. gonocephala by 100%, whereas the predator consumed nematodes in coarse gravel (19 nematodes within 3 h).     

Generation of murine stromal cell lines supporting hematopoietic stem cell proliferation by use of recombinant retrovirus vectors encoding simian virus 40 large T antigen.

The bone marrow is a complex microenvironment made up of multiple cell types which appears to play an important role in the maintenance of hematopoietic stem cell self-renewal and proliferation. We used murine long-term marrow cultures and a defective recombinant retrovirus vector containing the simian virus 40 large T antigen to immortalize marrow stromal cells which can support hematopoiesis in vitro for up to 5 weeks. Such cloned cell lines differentially supported stem cells which, when transplanted, allowed survival of lethally irradiated mice, formed hematopoietic spleen colonies in vivo, and stimulated lymphocyte proliferation in vitro. Molecular and functional analyses of these cell lines did not demonstrate the production of any growth factors known to support the proliferation of primitive hematopoietic stem cells. All cell lines examined produced macrophage colony-stimulating factor. The use of immortalizing retrovirus vectors may allow determination of unique cellular proteins important in hematopoietic stem cell proliferation by the systematic comparison of stromal cells derived from a variety of murine tissues.