The mitochondrial citrate/isocitrate carrier plays a regulatory role in glucose-stimulated insulin secretion.

Glucose-stimulated insulin secretion (GSIS) is mediated in part by glucose metabolism-driven increases in ATP/ADP ratio, but by-products of mitochondrial glucose metabolism also play an important role. Here we investigate the role of the mitochondrial citrate/isocitrate carrier (CIC) in regulation of GSIS. Inhibition of CIC activity in INS-1-derived 832/13 cells or primary rat islets by the substrate analogue 1,2,3-benzenetricarboxylate (BTC) resulted in potent inhibition of GSIS, involving both first and second phase secretion. A recombinant adenovirus containing a CIC-specific siRNA (Ad-siCIC) dose-dependently reduced CIC expression in 832/13 cells and caused parallel inhibitory effects on citrate accumulation in the cytosol. Ad-siCIC treatment did not affect glucose utilization, glucose oxidation, or ATP/ADP ratio but did inhibit glucose incorporation into fatty acids and glucose-induced increases in NADPH/NADP+ ratio relative to cells treated with a control siRNA virus (Ad-siControl). Ad-siCIC also inhibited GSIS in 832/13 cells, whereas overexpression of CIC enhanced GSIS and raised cytosolic citrate levels. In normal rat islets, Ad-siCIC treatment also suppressed CIC mRNA levels and inhibited GSIS. We conclude that export of citrate and/or isocitrate from the mitochondria to the cytosol is an important step in control of GSIS

Minimal short-term effect of dietary 2'-fucosyllactose on bacterial colonisation, intestinal function and necrotising enterocolitis in preterm pigs

AbstractHuman milk decreases the risk of necrotising enterocolitis (NEC), a severe gastrointestinal disease that occurs in 5–10 % of preterm infants. The prebiotic and immune-modulatory effects of milk oligosaccharides may contribute to this protection. Preterm pigs were used to test whether infant formula enriched with α1,2-fucosyllactose (2'-FL, the most abundant oligosaccharide in human milk) would benefit gut microbial colonisation and NEC resistance after preterm birth. Caesarean-delivered preterm pigs were fed formula (Controls, n 17) or formula with 5 g/l 2'-FL (2'-FL, n 16) for 5 d; eight 2'-FL pigs (50 %) and twelve Controls (71 %) developed NEC, with no difference in lesion scores (P=0·35); 2'-FL pigs tended to have less anaerobic bacteria in caecal contents (P=0·22), but no difference in gut microbiota between groups were observed by fluorescence in situ hybridisation and 454 pyrosequencing. Abundant α1,2-fucose was detected in the intestine with no difference between groups, and intestinal structure (villus height, permeability) and digestive function (hexose absorption, brush border enzyme activities) were not affected by 2'-FL. Formula enrichment with 2'-FL does not affect gut microbiology, digestive function or NEC sensitivity in pigs within the first few days after preterm birth. Milk 2'-FL may not be critical in the immediate postnatal period of preterm neonates when gut colonisation and intestinal immunity are still immature.</jats:p

Benefit of respiratory gating in the Danish Breast Cancer Group partial breast irradiation trial

Background and purpose: Partial breast irradiation (PBI)has beenthe Danish Breast Cancer Group(DBCG) standard for selected breast cancer patients since 2016 based onearlyresults from the DBCG PBI trial.During trial accrual, respiratory-gated radiotherapy was introduced in Denmark. This study aims to investigate the effect of respiratory-gating on mean heart dose (MHD).Patients and methods: From 2009 to 2016 the DBCG PBI trial included 230 patientswith left-sided breast cancer receiving external beam PBI, 40 Gy/15 fractions/3 weeks.Localization of the tumor bed on the planning CT scan, the use of respiratory-gating, coverage of the clinical target volume (CTV), and doses to organs at risk were collected.Results: Respiratory-gating was used in 123 patients (53 %). In 176 patients (77 %) the tumor bed was in the upper and in 54 patients (23 %) in the lower breast quadrants. The median MHD was 0.37 Gy (interquartile range 0.26-0.57 Gy), 0.33 Gy (0.23-0.49 Gy) for respiratory-gating, and 0.49 Gy (0.31-0.70 Gy) for free breathing, p &lt; 0.0001. MHD was &lt; 1 Gy in 206 patients (90 %) and &lt; 2 Gy in 221 patients (96 %). Respiratory-gating led to significantly lower MHD for upper-located, but not for lower-located tumor beds, however, all MHD were low irrespective of respiratory-gating. Respiratory-gating did not improve CTV coverage or lower lung doses.Conclusions: PBI ensured a low MHD for most patients. Adding respiratory-gating further reduced MHD for upper-located but not for lower-located tumor beds but did not influence target coverage or lung doses. Respiratory-gating is no longer DBCG standard for left-sided PBI

Sustainable bioethanol production combining biorefinery principles using combined raw materials from wheat undersown with clover-grass

To obtain the best possible net energy balance of the bioethanol production the biomass raw materials used need to be produced with limited use of non-renewable fossil fuels. Intercropping strategies are known to maximize growth and productivity by including more than one species in the crop stand, very often with legumes as one of the components. In the present study clover-grass is undersown in a traditional wheat crop. Thereby, it is possible to increase input of symbiotic fixation of atmospheric nitrogen into the cropping systems and reduce the need for fertilizer applications. Furthermore, when using such wheat and clover-grass mixtures as raw material, addition of urea and other fermentation nutrients produced from fossil fuels can be reduced in the whole ethanol manufacturing chain. Using second generation ethanol technology mixtures of relative proportions of wheat straw and clover-grass (15:85, 50:50, and 85:15) were pretreated by wet oxidation. The results showed that supplementing wheat straw with clover-grass had a positive effect on the ethanol yield in simultaneous saccharification and fermentation experiments, and the effect was more pronounced in inhibitory substrates. The highest ethanol yield (80% of theoretical) was obtained in the experiment with high fraction (85%) of clover-grass. In order to improve the sugar recovery of clover-grass, it should be separated into a green juice (containing free sugars, fructan, amino acids, vitamins and soluble minerals) for direct fermentation and a fibre pulp for pretreatment together with wheat straw. Based on the obtained results a decentralized biorefinery concept for production of biofuel is suggested emphasizing sustainability, localness, and recycling principle

Rapid Hydrogen Shift Scrambling in Hydroperoxy-Substituted Organic Peroxy Radicals

Using quantum mechanical calculations, we have investigated hydrogen shift (H-shift) reactions in peroxy radicals derived from the atmospheric oxidation of 1-pentene (CH_2═CHCH_2CH_2CH_3) and its monosubstituted derivatives. We investigate the peroxy radicals, HOCH_2CH(OO)CR_1HCH_2CH_3, HOCH_2CH(OO)CH_2CR_1HCH_3, and HOCH_2CH(OO)CH_2CH_2CR_1H_2, where the substituent R_1 is an alcoholic (OH), a hydroperoxy (OOH), or a methoxy (OCH_3) group. For peroxy radicals with an OOH substituent, the H-shift reaction from the hydrogen atom on the OOH group to the OO group is extremely fast. We find that the rate constants of this type of H-shift reactions are greater than 10^3 s^(–1) for both the forward and the reverse reactions. It leads to the formation of two different radical isomers that react through different reaction mechanisms and yield different products. These very fast H-shift reactions are much faster than the reactions with NO and HO_2 under most atmospheric conditions and must be included in the atmospheric modeling of volatile organic compounds where hydroperoxy peroxy radicals are formed