Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations

Phospho- and sphingolipids are crucial cellular and intracellular compounds. These lipids are required for active transport, a number of enzymatic processes, membrane formation, and cell signalling. Disruption of their metabolism leads to several diseases, with diverse neurological, psychiatric, and metabolic consequences. A large number of phospholipid and sphingolipid species can be detected and measured in human plasma. We conducted a meta-analysis of five European family-based genome-wide association studies (N = 4034) on plasma levels of 24 sphingomyelins (SPM), 9 ceramides (CER), 57 phosphatidylcholines (PC), 20 lysophosphatidylcholines (LPC), 27 phosphatidylethanolamines (PE), and 16 PE-based plasmalogens (PLPE), as well as their proportions in each major class. This effort yielded 25 genome-wide significant loci for phospholipids (smallest P-value = 9.88×10⁻²⁰⁴) and 10 loci for sphingolipids (smallest P-value = 3.10×10⁻⁵⁷). After a correction for multiple comparisons (P-value<2.2×10⁻⁹), we observed four novel loci significantly associated with phospholipids (PAQR9, AGPAT1, PKD2L1, PDXDC1) and two with sphingolipids (PLD2 and APOE) explaining up to 3.1% of the variance. Further analysis of the top findings with respect to within class molar proportions uncovered three additional loci for phospholipids (PNLIPRP2, PCDH20, and ABDH3) suggesting their involvement in either fatty acid elongation/saturation processes or fatty acid specific turnover mechanisms. Among those, 14 loci (KCNH7, AGPAT1, PNLIPRP2, SYT9, FADS1-2-3, DLG2, APOA1, ELOVL2, CDK17, LIPC, PDXDC1, PLD2, LASS4, and APOE) mapped into the glycerophospholipid and 12 loci (ILKAP, ITGA9, AGPAT1, FADS1-2-3, APOA1, PCDH20, LIPC, PDXDC1, SGPP1, APOE, LASS4, and PLD2) to the sphingolipid pathways. In large meta-analyses, associations between FADS1-2-3 and carotid intima media thickness, AGPAT1 and type 2 diabetes, and APOA1 and coronary artery disease were observed. In conclusion, our study identified nine novel phospho- and sphingolipid loci, substantially increasing our knowledge of the genetic basis for these traits.     

Plants used as natural dye sources in Turkey

This study was carried out in the regions where handcrafts such as carpet and rug weaving are common in Turkey. In the regions where natural dyes are used, 123 plant species belonging to 50 families were identified as sources of natural dyes. In natural dye production, different parts of the plant or the whole aboveground plant is used. Ten different colors are gained from the plants. Sometimes the same color can be obtained from different plants. By mixing different plants, it is possible to produce various colors. We also identified more than 12 natural and more than eight chemical assistant substances (mordant) that are used in the regions to bind dye to fibers, to maintain the strongness and brightness of the colors, and to obtain various colors     

Recent advances in chemistry,therapeutic properties and sources of polydatin

Polydatin (PLD), the 3-O-β-glucopyranoside of the well-known stilbenoid compound resveratrol, is a major compound of Fallopia japonica (Houtt.) R. Decr. (Japanese knotweed), which is widely used in traditional Chinese medicine to treat infection, inflammatory diseases and circulatory problems. It has shown a wide range of biological activities including anti-inflammatory, anti-oxidant, anti-cancer, neuroprotective, hepatoprotective, nephroprotective and immunostimulatory effects. Although resveratrol has similar beneficial effects, its low bioavailability has remained a problem. Glycosylation increases solubility of resveratrol in an aqueous environment, thus improving its bioavailability. This has led to a growing interest in PLD. Promising results obtained from bioactivity studies have boosted an intense research on this compound. The aim of this review is to give a comprehensive overview of the botanical sources, pharmacology, biosynthesis, biotechnological production, and bioactivities of PLD, and to discuss clinical studies on this compound.     

Serum and hair zinc levels in epileptic children taking valproic acid

This study was performed to investigate the serum and hair zinc levels in patients having epilepsy diagnoses who were intended to be put on valproic acid (VA) monotherapy and had never ingested antiepileptics before. A total of 16 patients having normal growth, development, and nutrition was selected as Group 1, and Group 2 was made up of 10 patients who had received VA monotherapy for 2 yrs or more and had normal growth, development, and nutrition characteristics. A control group (Group 3) was formed of 15 subjects who applied to the hospital for upper respiratory tract disorders. Serum and hair samples were taken for zinc assays from the Group 1 patients on the d 0, 15, 30, 45, 60, 75, and 180. Groups 2 and 3 were sampled only once, and zinc levels were determined. We found that both serum and hair zinc levels in Group 1 were higher than those of Group 2 and control group before the beginning of VA therapy, but they returned to normal during VA treatment. There was no zinc deficiency, and zinc replacement treatment may therefore be considered as unnecessary.     

Late‐in‐life treadmill training rejuvenates autophagy,protein aggregate clearance,and function in mouse hearts

Protein quality control mechanisms decline during the process of cardiac aging. This enables the accumulation of protein aggregates and damaged organelles that contribute to age‐associated cardiac dysfunction. Macroautophagy is the process by which post‐mitotic cells such as cardiomyocytes clear defective proteins and organelles. We hypothesized that late‐in‐life exercise training improves autophagy, protein aggregate clearance, and function that is otherwise dysregulated in hearts from old vs. adult mice. As expected, 24‐month‐old male C57BL/6J mice (old) exhibited repressed autophagosome formation and protein aggregate accumulation in the heart, systolic and diastolic dysfunction, and reduced exercise capacity vs. 8‐month‐old (adult) mice (all p < 0.05). To investigate the influence of late‐in‐life exercise training, additional cohorts of 21‐month‐old mice did (old‐ETR) or did not (old‐SED) complete a 3‐month progressive resistance treadmill running program. Body composition, exercise capacity, and soleus muscle citrate synthase activity improved in old‐ETR vs. old‐SED mice at 24 months (all p < 0.05). Importantly, protein expression of autophagy markers indicate trafficking of the autophagosome to the lysosome increased, protein aggregate clearance improved, and overall function was enhanced (all p < 0.05) in hearts from old‐ETR vs. old‐SED mice. These data provide the first evidence that a physiological intervention initiated late‐in‐life improves autophagic flux, protein aggregate clearance, and contractile performance in mouse hearts.     

Determination of fatty acid profiles,cholesterol and D,E, K vitamin’s content in Astacus leptodactylus caught from wild prior to reproduction period

In this study, fatty acids compositions, fat-soluble vitamins (D, E, and K) and cholesterol in the gonads, hepatopancreas, and abdomen muscle of male and female Astacus leptodactylus caught from wild were determined in their prior of reproduction period. The results showed that in female A. leptodactylus, compared with hepatopancreas, the ovaries contained a significantly high level of C16:0, C16:1n-7, C18:1n-9, C22:6n-3, the ratio of n-3 to n-6 (p < 0.05). In females, the values of δ-tocopherol, α-tocopherol, K₂ and D₂ vitamins, and cholesterol obtained in ovaries were significantly higher than those of obtained in abdomen muscle and hepatopancreas (p < 0.05). In male A. leptodactylus δ-tocopherol was found to be 1.91 μg/g in testes, which is significantly higher than that of abdomen muscle, hepatopancreas, and vasa deferentia (p < 0.05). In conclusion, the findings of present study are especially constructive for both crayfish biologists and farmers for preparing broodstock diets for crayfish at reproduction units.     

Chronotype and its relationship with sleep disorders in children with attention deficit hyperactivity disorder

Chronotype can be classified as morningness types, people who prefer morning hours for their physical and mental activities; eveningness types, people who prefer the afternoon or evening hours; and intermediate types, those who show characteristics of both morningness and eveningness types. Attention deficit hyperactivity disorder (ADHD) has been linked with disturbances in chronotype, particularly increased eveningness. Despite the possibility of an association between chronotypes, sleep disturbances and ADHD symptoms, there is little evidence of this association considering the child population. The purpose of this study was to examine chronotype preferences in children aged between 7 and 12 years who were diagnosed as having ADHD in the context of sleep disturbances. The Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version, Conner’s Rating Scales, Children’s Sleep Habit Questionnaire and Children’s Chronotype Questionnaire were used for the evaluation of children with ADHD and healthy controls. The ADHD group was 73% combined-type, and the eveningness scores of the ADHD group (n = 52) were significantly higher than the control group (n = 52) (p < 0.01). There was a positive correlation between the higher scores of eveningness and total scores on resistance to sleep time (p < 0.09), respiratory problems during sleep and daytime sleepiness in the ADHD group. CSHQ total score was found to be a predictive factor for eveningness among children with ADHD (p < 0.01). These findings highlight possible reciprocal links between ADHD symptoms, sleep disturbances and chronotype in children aged 7–12 years, which might lead to individualized treatment options.     

Cytoglobin: a potential marker for adipogenic differentiation in preadipocytes in vitro

Obesity, mainly characterized by the excess fat storage, is a global health problem resulting in serious morbidity and mortality. Identification of molecular mechanisms in adipogenic differentiation pathway might lead to development of new strategies for diagnosis, prevention and therapy of obesity and associated diseases. Discovery of new genes and proteins in the differentiation pathway could help to understand the key specific regulators of the adipogenesis. Cytoglobin (Cygb), identified as a new globin family member protein, is expressed in various tissues. Although its interaction with oxygen and nitric oxide indicates the potential role in antioxidant pathways, the exact role remains unclear. In the current study, expression level of Cygb was determined in proliferating and differentiating 3T3-F442A cells by gene expression and protein expression analysis. Results revealed that Cygb expression up-regulated in differentiated cells in parallel with adipogenic differentiation markers; PPARγ, CEBPα and FABP4 expressions. Besides, Cygb overexpression in preadipocytes contributed to the adipogenic differentiation as verified by detection of higher lipid droplets and increased PPARγ, CEBPα and FABP4 expressions with respect to control cells. These findings will shed light on the unknown roles of Cygb in adipogenesis and obesity.