Golgi screen identifies the RhoGEF Solo as a novel regulator of RhoB and endocytic transport.

The control of intracellular membrane trafficking by Rho GTPases is central to cellular homeostasis. How specific guanine nucleotide exchange factors and GTPase-activating proteins locally balance GTPase activation in this process is nevertheless largely unclear. By performing a microscopy-based RNAi screen, we here identify the RhoGEF protein Solo as a functional counterplayer of DLC3, a RhoGAP protein with established roles in membrane trafficking. Biochemical, imaging and optogenetics assays further uncover Solo as a novel regulator of endosomal RhoB. Remarkably, we find that Solo and DLC3 control not only the activity, but also total protein levels of RhoB in an antagonistic manner. Together, the results of our study uncover the first functionally connected RhoGAP-RhoGEF pair at endomembranes, placing Solo and DLC3 at the core of endocytic trafficking.

Bioavailability Study of Maqui Berry Extract in Healthy Subjects.

Several health promoting effects have been reported for maqui berry, rich in anthocyanins. Direct effects of anthocyanins as well as bioactive metabolites might be involved. Within the study, bioavailability of a proprietary standardized maqui berry extract Delphinol® was investigated based on two selected anthocyanins (delphinidin-3-O-glucoside (DS) + cyanidin-3-O-sambubioside (CS)) and two breakdown products (protocatechuic acid (PCA) + gallic acid (GA)) after a single-dose supplementation in humans. Pharmacokinetic parameters were calculated from individual concentration time curves. In all 12 subjects a significant increase was noted in plasma values of DG and CS after intake of maqui berry extract. Maximum concentration of DG was observed after 1.0 ± 0.3 h and CS after 2.0 ± 1.1 h. Within 8 h, concentrations nearly returned to baseline levels. The results confirm a fast uptake and metabolism of the two selected key substances. Additionally, the phenolic acids GA and PCA were observed as breakdown products of anthocyanins. In summary, the study clearly confirms the bioavailability of maqui berry extract and its specific anthocyanin compounds and related breakdown products in healthy subjects.

Blood glucose response after oral intake of lactulose in healthy volunteers: A randomized, controlled, cross-over study.

AIM: To investigate possible changes of blood glucose levels after oral intake of lactulose in healthy subjects. METHODS: The study was performed as prospective, randomized, two-part study with 4-way cross-over design with n = 12 in each study arm. Capillary blood glucose levels were determined over a time period of 180 min after intake of a single dose of 10 g or 20 g lactulose provided as crystal or liquid formulation. During the manufacturing process of lactulose, impurities with sugars (e.g., lactose, fructose, galactose) occur. Water and 20 g glucose were used as control and reference. Because lactulose is used as a functional food ingredient, it may also be consumed by people with impaired glucose tolerance, including diabetics. Therefore, it is of interest to determine whether the described carbohydrate impurities may increase blood glucose levels after ingestion. RESULTS: The blood glucose concentration-time curves after intake of 10 g lactulose, 20 g lactulose, and water were almost identical. None of the three applications showed any changes in blood glucose levels. After intake of 20 g glucose, blood glucose concentration increased by approximately 3 mmol/L (mean Cmax = 8.3 mmol/L), reaching maximum levels after approximately 30 min and returning to baseline within approximately 90 min, which was significantly different to the corresponding 20 g lactulose formulations (P < 0.0001). Comparing the two lactulose formulations, crystals and liquid, in the dosage of 10 g and 20 g, there was no difference in the blood glucose profile and calculated pharmacokinetic parameters despite the different amounts of carbohydrate impurities (1.5% for crystals and 26.45% for liquid). Anyhow, the absolute amount of single sugars was low with 0.3 g in crystals and 5.29 g in liquid formulation in the 20 g dosages. Lactulose was well tolerated by most volunteers, and only some reported mild to moderate mainly gastrointestinal side effects. CONCLUSION: The unchanged blood glucose levels after lactulose intake in healthy subjects suggest its safe use in subjects with impaired glucose tolerance.