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Physical activity increases muscle protein synthesis rates. However, the impact of exercise on the coordinated up- and/or downregulation of individual protein synthesis rates in skeletal muscle tissue remains unclear. The authors assessed the impact of exercise on mixed muscle, myofibrillar, and mitochondrial protein synthesis rates as well as individual protein synthesis rates in vivo in rats. Adult Lewis rats either remained sedentary (n = 3) or had access to a running wheel (n = 3) for the last 2 weeks of a 3-week experimental period. Deuterated water was injected and subsequently administered in drinking water over the experimental period. Blood and soleus muscle were collected and used to assess bulk mixed muscle, myofibrillar, and mitochondrial protein synthesis rates using gas chromatography–mass spectrometry and individual muscle protein synthesis rates using liquid chromatography–mass spectrometry (i.e., dynamic proteomic profiling). Wheel running resulted in greater myofibrillar (3.94 ± 0.26 vs. 3.03 ± 0.15%/day; p <.01) and mitochondrial (4.64 ± 0.24 vs. 3.97 ± 0.26%/day; p <.05), but not mixed muscle (2.64 ± 0.96 vs. 2.38 ± 0.62%/day; p =.71) protein synthesis rates, when compared with the sedentary condition. Exercise impacted the synthesis rates of 80 proteins, with the difference from the sedentary condition ranging between −64% and +420%. Significantly greater synthesis rates were detected for F1-ATP synthase, ATP synthase subunit alpha, hemoglobin, myosin light chain-6, and synaptopodin-2 (p <.05). The skeletal muscle protein adaptive response to endurance-type exercise involves upregulation of mitochondrial protein synthesis rates, but it is highly coordinated as reflected by the up- and downregulation of various individual proteins across different bulk subcellular protein fractions. [ABSTRACT FROM AUTHOR]

Our understanding of complex biological processes can be enhanced by combining different kinds of high-throughput experimental data, but the use of incompatible identifiers makes data integration a challenge. We aimed to improve methods for integrating and visualizing different types of omics data. To validate these methods, we applied them to two previous studies on starvation in mice, one using proteomics and the other using transcriptomics technology. We extended the PathVisio software with new plugins to link proteins, transcripts and pathways. A low overall correlation between proteome and transcriptome data was detected (Spearman rank correlation: 0.21). At the level of individual genes, correlation was highly variable. Many mRNA/protein pairs, such as fructose biphosphate aldolase B and ATP Synthase, show good correlation. For other pairs, such as ferritin and elongation factor 2, an interesting effect is observed, where mRNA and protein levels change in opposite directions, suggesting they are not primarily regulated at the transcriptional level. We used pathway diagrams to visualize the integrated datasets and found it encouraging that transcriptomics and proteomics data supported each other at the pathway level. Visualization of the integrated dataset on pathways led to new observations on gene-regulation in the response of the gut to starvation. Our methods are generic and can be applied to any multi-omics study. The PathVisio software can be obtained at http://www.pathvisio.org. Supplemental data are available at http://www.bigcat.unimaas.nl/data/jib-supplemental/, including instructions on reproducing the pathway visualizations of this manuscript.

Context: Long-term weight loss (WL) maintenance is the biggest challenge for overweight and obesity because of the almost unavoidable phenomenon of partial or even total weight regain (WR) after WL. Objective: In the present study we investigated the relations of (the changes of) adipocyte size and other risk biomarkers with WR during the follow-up of the Yoyo dietary intervention. Methods: In this randomized controlled study, 48 overweight/obese participants underwent a very-low-calorie diet to lose weight, followed by a weight-stable period of 4 weeks and a follow-up period of 9 months. Anthropometric measurements, adipocyte volume of abdominal subcutaneous adipose tissue, and plasma metabolic parameters (free fatty acids [FFAs], triglycerides [TGs], total cholesterol, glucose, insulin, homeostasis model assessment of insulin resistance [HOMA-IR], interleukin 6 [IL-6], angiotensin-converting enzyme [ACE] activity, retinol binding protein 4 [RBP4]) at the beginning and the end of follow-up were analyzed. Results: Our results show that changes of TGs, IL-6, HOMA-IR, and ACE are significantly positively correlated with WR. Multiple linear regression analysis shows that only TG and IL-6 changes remained significantly correlated with WR and increased body fat mass. Moreover, the change in HOMA-IR was tightly correlated with the change in TGs. Surprisingly, change in adipocyte volume during follow-up was not correlated with WR nor with other factors, but positive correlations between adipocyte volume and HOMA-IR were found at the beginning and end of the follow-up. Conclusion: These results suggest that TGs and IL-6 are independently linked to WR via separate mechanisms, and that HOMA-IR and adipocyte volume may indirectly link to WR through the change of plasma TGs. [ABSTRACT FROM AUTHOR]

Limb mammary syndrome (LMS), mapped to human chromosome 3q27, is a newly described genetic disorder involving ectrodactyly, mammary hypoplasia, and other hand/foot anomalies. It overlaps with the ulnar mammary syndrome (UMS) and a clefting syndrome, but allelism with these has been excluded. A large Dutch family with the syndrome has been studied. No mutations were found in the SOX2 (ital) open reading frame, but the SOX2 (ital) gene at 3q27 seems like an excellent candidate: the corresponding protein simulates FGF4 (ital) expression and the protein is one that is important for signaling in limb development/outgrowth. .

Mouse models show that congenital neural tube defects (NTDs) can occur as a result of mutations in the platelet-derived growth factor receptor-[Alpha] gene (PDGFR[Alpha]). Mice heterozygous for the PDGFR[Alpha]-mutation Patch, and at the same time homozygous for the undulated mutation in the Paxl gene, exhibit a high incidence of lumbar spina bifida occulta, suggesting a functional relation between PDGFR[Alpha] and Pax1. Using the human PDGFR[Alpha] promoter linked to a luciferase reporter, we show in the present paper that Paxl acts as a transcriptional activator of the PDGFR[Alpha] gene in differentiated Tera-2 human embryonaL carcinoma cells. Two mutant Pax1 proteins carrying either the undulated.mutation or the Gin [right arrow] His mutation previously identified by us in the PAX1 gene of a patient with spina bifida, were not or less effective, respectively. Surprisingly, Pax1 mutant proteins appear to have opposing transcriptional activities in undifferentiated Tera-2 cells as well as in the U-2 OS osteosarcoma cell line. In these cells, the mutant Pax1 proteins enhance PDGFR[Alpha]-promoter activity whereas the wild-type protein does not. The apparent up-regulation of PDGFR[Alpha] expression in these cells clearly demonstrates a gain-of-function phenomenon associated with mutations in Pax genes. The altered transcriptional activation properties correlate with altered protein-DNA interaction in band-shift assays. Our data provide additional evidence that mutations in Pax1 can act as a risk factor for NTDs and suggest that the PDGFR[Alpha] gene is a direct target of Pax1. In addition, the results support the hypothesis that deregulated PDGFR[Alpha] expression may be causally related to NTDs.

A pathological mutation has been reported for the first time in a nuclear complex I gene of the mitochondrial respiratory chain. Twenty complex I-deficient patients with multisystem disorders have been studied. For the human nuclear gene that encodes with 18-kD (AQDQ) subnuit of the mitochondrial respiratory chain complex I, an identified mutation, cDNA cloning, chromosomal localization have been reported. The gene of the cDNA has been mapped to chromosome 5. A homozygous 5-bp duplication was found in a complex I-deficient child with parents heterozygous for the mutation. The duplication was in the 18-kD cDNA and destroys a consensus phosphorylation site. The patient had normal muscle morphology and a surprisingly nonspecific fatal progressive phenotype and no increased lactate concentrations in body fluids. In 19 patients who were complex I-deficient, mutations were not found in the 18-kD gene.