Targeted degradation of zDHHC-PATs decreases substrate S-palmitoylation.

Reversible S-palmitoylation of protein cysteines, catalysed by a family of integral membrane zDHHC-motif containing palmitoyl acyl transferases (zDHHC-PATs), controls the localisation, activity, and interactions of numerous integral and peripheral membrane proteins. There are compelling reasons to want to inhibit the activity of individual zDHHC-PATs in both the laboratory and the clinic, but the specificity of existing tools is poor. Given the extensive conservation of the zDHHC-PAT active site, development of isoform-specific competitive inhibitors is highly challenging. We therefore hypothesised that proteolysis-targeting chimaeras (PROTACs) may offer greater specificity to target this class of enzymes. In proof-of-principle experiments we engineered cell lines expressing tetracycline-inducible Halo-tagged zDHHC5 or zDHHC20, and evaluated the impact of Halo-PROTACs on zDHHC-PAT expression and substrate palmitoylation. In HEK-derived FT-293 cells, Halo-zDHHC5 degradation significantly decreased palmitoylation of its substrate phospholemman, and Halo-zDHHC20 degradation significantly diminished palmitoylation of its substrate IFITM3, but not of the SARS-CoV-2 spike protein. In contrast, in a second kidney derived cell line, Vero E6, Halo-zDHHC20 degradation did not alter palmitoylation of either IFITM3 or SARS-CoV-2 spike. We conclude from these experiments that PROTAC-mediated targeting of zDHHC-PATs to decrease substrate palmitoylation is feasible. However, given the well-established degeneracy in the zDHHC-PAT family, in some settings the activity of non-targeted zDHHC-PATs may substitute and preserve substrate palmitoylation.

Dietary Patterns and Overweight/Obesity: A Review Article.

BACKGROUND: Dietary patterns analysis may provide insights into the influence of overall diet on overweight/obesity. In the past two decades, the relation between dietary patterns and overweight/obesity has been a research focus and a number of results were reported in the research field. METHODS: An electronic literature search was conducted in PubMed and Web of Science, to identify human studies published by Mar 2015 and written in English. The following keywords or phrases were involved: dietary patterns, dietary pattern, factor analysis, principal component analysis, diet, obesity, adiposity, overweight and BMI. All the studies were retrieved and prudent/healthy (n=17) and western/unhealthy (n=18) dietary patterns were identified. RESULTS: When compared with the lowest categories of a prudent/healthy dietary pattern, a reduced overweight/obesity risk was shown in the highest (OR=0.64; 95% CI: 0.52, 0.78; P<0.0001). While there was an increased overweight/obesity risk in the highest when compared with the lowest categories of a western/unhealthy dietary pattern (OR=1.65; 95% CI: 1.45, 1.87; P<0.0001). CONCLUSION: A prudent/healthy dietary pattern and limit intake of western/unhealthy dietary pattern should be followed, which helps to keep a healthy body mass.

Rural-Urban Differences of Dietary Patterns, Overweight, and Bone Mineral Status in Chinese Students.

China is an urban and rural social model country. In the past three decades, the developing speed of rural areas has been much slower than urban areas, which may lead to the differences in dietary patterns. This study aimed to investigate the disparities of dietary structures from urban and rural children, and to analyze the effects of different dietary patterns on their adverse outcome. Among 1590 students, aged 11 years to 17 years, from primary and middle schools, a cross-sectional study was conducted. There were three dietary patterns recognized: Westernization structure, meat diet structure, and Western and Chinese structure. Compared with rural students, more urban students were in the highest categories of the whole dietary patterns (p < 0.001). Overweight/obesity and central adiposity were more prevailing among urban students, while rural students had a more prevailing risk of bone fracture (p < 0.05). Through the adjustment for all confounding factors, the Westernization structure could increase the risk of overweight/obesity and central adiposity, the meat structure could increase the risk of elevated blood pressure/hypertension, while the risk of low bone mineral quality could be reduced by the Chinese and Western structure. In conclusion, a rural-urban disparity in dietary patterns was found in our study, and different dietary patterns were associated with the risk of some adverse outcomes. Therefore, there were different prevalences of the adverse outcomes between rural and urban students.

The complete mitochondrial genome of Sus cebifrons (Sus, Suidae).

In this work, we report the complete mitochondrial genome sequence of Sus cebifrons (Visayan warty pig). The total length of the mitogenome was 16,475 bp, and its overall base composition was estimated to be 35.0% for A, 25.8% for T, 26.2% for C and 13.0% for G, indicating an A-T (60.8%)-rich feature in Sus cebifrons mitogenome. It contained the typical structure of 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and a noncoding control region (D-loop region). The arrangement of these genes was the same as that found in other pigs. The complete mitochondrial genome sequence of the Sus cebifrons would provide new genetic resources for pig domestication study.

Birth weight and subsequent risk of asthma: a systematic review and meta-analysis.

BACKGROUND: Previous studies suggest that birth weight is related to later risk of asthma. However, few meta-analyses have investigated these associations. Therefore, we performed a meta-analysis with different classifications to further validate the relationship between birth weight and asthma. METHODS: PubMed (1990-2013), ScienceDirect (1990-2013), EMBASE(1990-2013),EBSCO (1990-2013) and Springer (1990-2013) were searched for articles. The following MeSH terms were used: "birth weight", "fetal growth retardation", "intrauterine growth restriction", "asthma", "wheezing". RESULTS: We included 18 studies with data from a total of over 90,000 children and adults. (1) Low birth weight (<2,500g) as compared with BW>2,500g and BW=2500-4000g was associated with increased risk of asthma (Children: OR, 1.28; 95% CI, 1.09-1.50, P<0.05; OR, 1.34; 95% CI, 1.13-1.60, P<0.05, Adults: OR, 1.25; 95% CI, 1.12-1.39, P<0.05; OR, 1.25; 95% CI, 1.12-1.40, P<0.05). (2) High birth weight (>4,000g) was not associated with the risk of asthma when BW<4,000g and BW=2500-4000g were used as the reference. CONCLUSIONS: These results suggest that low birth weight (<2,500g) is associated with increased risk of asthma both in children and adults and may serve as a mediator between prenatal influences and later disease risk; but high birth weight (>4,000g) was not associated with increased risk of asthma.