Bioinformatics-driven identification and examination of candidate genes for non-alcoholic fatty liver disease

Objective

Candidate genes for non-alcoholic fatty liver disease (NAFLD) identified by a bioinformatics approach were examined for variant associations to quantitative traits of NAFLD-related phenotypes.

Research Design and Methods

By integrating public database text mining, trans-organism protein-protein interaction transferal, and information on liver protein expression a protein-protein interaction network was constructed and from this a smaller isolated interactome was identified. Five genes from this interactome were selected for genetic analysis. Twenty-one tag single-nucleotide polymorphisms (SNPs) which captured all common variation in these genes were genotyped in 10,196 Danes, and analyzed for association with NAFLD-related quantitative traits, type 2 diabetes (T2D), central obesity, and WHO-defined metabolic syndrome (MetS).

Results

273 genes were included in the protein-protein interaction analysis and EHHADH, ECHS1, HADHA, HADHB, and ACADL were selected for further examination. A total of 10 nominal statistical significant associations (P<0.05) to quantitative metabolic traits were identified. Also, the case-control study showed associations between variation in the five genes and T2D, central obesity, and MetS, respectively. Bonferroni adjustments for multiple testing negated all associations.

Conclusions

Using a bioinformatics approach we identified five candidate genes for NAFLD. However, we failed to provide evidence of associations with major effects between SNPs in these five genes and NAFLD-related quantitative traits, T2D, central obesity, and MetS.     

Effects of different male remating intervals on the reproductive success of Choristoneura rosaceana males and females

The mass of the spermatophore transferred by a previously mated Choristoneura rosaceana male increases with time elapsed since the last mating but, even after 4 days, it never reaches the mass of the spermatophore of a virgin male. However, spermatophore mass is clearly not a good indicator of the male reproductive investment as the quantity of sperm in the second ejaculate of a previously mated male is the same as that of his first, if he is allowed a 2 (eupyrene sperm) to 3 day (apyrene sperm) recovery period. The interval between the first two matings had no influence on female fecundity or longevity but significantly affected fertility if the male had only 1 day to recover. The length of the post-copulatory refractory period was also shorter in females mated with previously mated males than in those mated with virgins, regardless of the male's remating interval. Furthermore, a significant variation in the eupyrene sperm content of the spermatophore transferred by virgin males had no influence on the length of the female refractory period. Globally, these results support the hypothesis that a factor, other than sperm numbers in the spermatheca, is responsible for maintaining the inhibition of pheromone production in this species.     

Inhibition of the oxygen-evolving complex of photosystem II and depletion of extrinsic polypeptides by nickel

The toxic effect of Ni²⁺ on photosynthetic electron transport was studied in a photosystem II submembrane fraction. It was shown that Ni²⁺ strongly inhibits oxygen evolution in the millimolar range of concentration. The inhibition was insensitive to NaCl but significantly decreased in the presence of CaCl₂. Maximal chlorophyll fluorescence, together with variable fluorescence, maximal quantum yield of photosystem II, and flash-induced fluorescence decays were all significantly declined by Ni²⁺. Further, the extrinsic polypeptides of 16 and 24 kDa associated with the oxygen-evolving complex of photosystem II were depleted following Ni²⁺ treatment. It was deduced that interaction of Ni²⁺ with these polypeptides caused a conformational change that induced their release together with Ca²⁺ from the oxygen-evolving complex of photosystem II with consequent inhibition of the electron transport activity.     

Effects of dietary thia fatty acids on lipid composition, morphology and macrophage function of Atlantic salmon (Salmo salar L.) kidney

High lipid levels are being used in modern salmonid diets to promote rapid growth; however there is a limiting supply of the traditional fish oils as the fish farming industry expands. One way to utilize the lipid sources better, could be to find ways to stimulate fatty acid (FA) oxidation so that Atlantic salmon use more energy for muscle growth and less for storage in perivisceral adipose tissue. We have previously shown that dietary inclusion of the thia FA tetradecylthioacetic acid (TTA) promoted hepatic beta-oxidation and reduced total body lipid levels. However, dietary TTA also had some negative effects, leading to accumulation of sulfone and sulfoxide metabolites of TTA in the kidney and increasing mortality rates, particularly at low water temperatures. Therefore we also wish to investigate the effects of TTA on kidney function at high and low temperatures, including some immune system parameters. The production of leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) immunoreactive material from exogenously added arachidonic acid in isolated head kidney macrophages was affected by both diet and temperature. The phagocytic activity in these cells was reduced by DTA in the 12 degrees C group and there was significantly higher protein degradation in head kidney macrophages at 12 degrees C compared to 5 degrees C in all dietary groups. Interestingly, the incorporation of thia FAs in the kidney was higher at 5 degrees C (0.3% TTA and 0.6% DTA) than at 12 degrees C (0.1% TTA and 0.5% DTA). Additionally, there were lower levels of saturated FAs, while higher levels of polyunsaturated FAs (PUFAs) in the kidney of TTA fed fish at 5 degrees C. We also observed temperature-independent tubular dilatation and a reduction in the density of melanomacrophages of the kidney in salmon fed TTA. Nevertheless, the mRNA expression of some immune-relevant genes in head kidney tissue was not affected by TTA-inclusion in salmon diets. In conclusion, it is clear that 0.6% TTA-inclusion in the feed leads to changes in the kidney function particularly at low water temperatures.     

Comparing water-related plant functional traits among dominant grasses of the Colorado Plateau: Implications for drought resistance

Plant and Soil - Water is the primary limiting factor for plants in drylands, which are projected to become even drier with climate change. Plant functional traits related to water influences...     

The presence of meniscal lesions is a strong predictor of neuropathic pain in symptomatic knee osteoarthritis: a cross-sectional pilot study

Introduction

Pain in osteoarthritis (OA) has been classically attributed to joint structural damage. Disparity between the degree of radiographic structural damage and the severity of symptoms implies that factors other than the joint pathology itself contribute to the pain. Peripheral and central sensitization have been suggested as two of the underlying mechanisms that contribute to pain in OA. The aim of this study was to explore in symptomatic knee OA patients, the structural changes assessed by magnetic resonance imaging (MRI) that could be used as markers of neuropathic pain (NP).

Methods

This cross-sectional observational pilot study included 50 knee OA patients with moderate to severe pain (VAS ≥40) in the target knee. The presence of NP was determined based on the PainDETECT questionnaire. Among the 50 patients included, 25 had PainDETECT score ≤12 (unlikely NP), 9 had PainDETECT score between 13 and 18 (uncertain NP) and 16 had PainDETECT score ≥19 (likely NP). WOMAC, PainDETECT, and VAS pain scores as well as knee MRI were assessed.

Results

Data showed no significant difference in demographic characteristics between the three groups. However, a positive and statistically significant association was found between the WOMAC pain (P <0.001), function (P <0.001), stiffness (P = 0.007) and total (P <0.001) scores as well as higher VAS pain score (P = 0.023), and PainDETECT scores. Although no difference was found in the cartilage volume between groups, the presence of meniscal extrusion in both medial (P = 0.006) and lateral (P = 0.023) compartments, and presence of meniscal tears in the lateral compartment (P = 0.011), were significantly associated with increasing PainDETECT score. Moreover, the presence of bone marrow lesions in the lateral plateau and the extent of the synovial membrane thickness in the lateral recess were associated with increasing PainDETECT scores (P = 0.032, P = 0.027, respectively).

Conclusions

In this study, meniscal lesions, particularly extrusion, were found to be among the strongest risk factors for NP in knee OA patients.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01733277","term_id":"NCT01733277"}}NCT01733277. Registered 16 November 2012.     

A Thesaurus for Soil Invertebrate Trait-Based Approaches

Soil invertebrates are known to be much involved in soil behaviour and therefore in the provision of ecosystem services. Functional trait-based approaches are methodologies which can be used to understand soil invertebrates’ responses to their environment. They (i) improve the predictions and (ii) are less dependent on space and time. The way traits have been used recently has led to misunderstandings in the integration and interpretation of data. Trait semantics are especially concerned. The aim of this paper is to propose a thesaurus for soil invertebrate trait-based approaches. T-SITA, an Internet platform, is the first initiative to deal with the semantics of traits and ecological preferences for soil invertebrates. It reflects the agreement of a scientific expert community to fix semantic properties (e.g. definition) of approximately 100 traits and ecological preferences. In addition, T-SITA has been successfully linked with a fully operational database of soil invertebrate traits. Such a link enhances data integration and improves the scientific integrity of data.     

Implicit Processing of Visual Emotions Is Affected by Sound-Induced Affective States and Individual Affective Traits

The ability to recognize emotions contained in facial expressions are affected by both affective traits and states and varies widely between individuals. While affective traits are stable in time, affective states can be regulated more rapidly by environmental stimuli, such as music, that indirectly modulate the brain state. Here, we tested whether a relaxing or irritating sound environment affects implicit processing of facial expressions. Moreover, we investigated whether and how individual traits of anxiety and emotional control interact with this process. 32 healthy subjects performed an implicit emotion processing task (presented to subjects as a gender discrimination task) while the sound environment was defined either by a) a therapeutic music sequence (MusiCure), b) a noise sequence or c) silence. Individual changes in mood were sampled before and after the task by a computerized questionnaire. Additionally, emotional control and trait anxiety were assessed in a separate session by paper and pencil questionnaires. Results showed a better mood after the MusiCure condition compared with the other experimental conditions and faster responses to happy faces during MusiCure compared with angry faces during Noise. Moreover, individuals with higher trait anxiety were faster in performing the implicit emotion processing task during MusiCure compared with Silence. These findings suggest that sound-induced affective states are associated with differential responses to angry and happy emotional faces at an implicit stage of processing, and that a relaxing sound environment facilitates the implicit emotional processing in anxious individuals.