Metabolic pathways involved in lipogenesis from lactate and acetate in bovine adipose tissue: Effects of metabolic inhibitors

Metabolic inhibitors were used in vitro in an attempt to elucidate the biochemical pathways by which lactate is converted to fatty acids by bovine adipose tissue. Subcutaneous adipose tissue samples were obtained by biopsy techniques from steers fed a high-energy ration. Kynurenate (α-2-diamino-γ-oxabenzenebutanoic acid) (5–10 mm), an inhibitor of acetyl-CoA carboxylase, and cerulenin (2,3-epoxy-4-oxo-7,10-dodecadienamide) (20–100 μg/ml), an inhibitor of the fatty acid synthetase enzyme complex, inhibited fatty acid synthesis from both acetate and lactate. The hydrogen acceptor, N-methylphenazonium methosulfate (10 μm) inhibited acetate but not lactate incorporation into fatty acids. α-Cyanohydroxycinnamate (5 mm) and phenylpyruvate (10 mm), which inhibit pyruvate entry into the mitochondria and pyruvate carboxylase, respectively, decreased lipogenesis from both acetate and lactate. The effects of phenylpyruvate on lipogenesis from acetate were greater in the presence of glucose plus insulin. Agaric acid (2-hydroxy-1,2,3-nonadecanetricarboxylic acid) (0.2 and 1.0 mm), which inhibits citrate efflux from the mitochondria also decreased lipogenesis from both acetate and lactate. Fluoroacetate (2.5 mm), an inhibitor of aconitate hydratase, had no effect on lipogenesis from acetate; but, in the presence of glucose or pyruvate, decreased lactate incorporation into fatty acids. n-Butylmalonate (5 mm), which blocks malate transport across the mitochondrial membrane, decreased lipogenesis from lactate but not acetate. Malate transport during lipogenesis is not associated with an operative malate:asparate shuttle in bovine adipose tissue, as indicated by the lack of effect of either 0.2 or 1.0 mm aminooxyacetate, a transaminase inhibitor, on lipogenesis from acetate or lactate. The results suggest a functional ATP-citrate lyase:NADP-malate dehydrogenase pathway in bovine subcutaneous adipose tissue and that this pathway may be involved in lipogenesis from acetate as well as lactate.     

Modification of cardiac activity in response to dehydration in the terrestrial slug, Limax maximus

The level of body hydration in the terrestrial slug Limax maximus modifies several aspects of behavior such as pneumostome activity, feeding responsiveness, huddling, and contact-rehydration. The relationship between water balance and pneumostome activity and respiratory function suggested that cardiac activity might also be affected. To pursue this possibility, intact slugs and isolated heart-central nervous system (CNS) preparations were used to investigate cardiac responses to the increase in hemolymph osmolality which occurs during dehydration. In intact animals, heart rate increased in response to progressive air-dehydration and to increases in hemolymph osmolality resulting from injections of hyperosmotic solutions of mannitol or NaCl. In isolated preparations, the heart or CNS were separately exposed to hyperosmotic saline. Exposure of the heart alone to hyperosmotic saline resulted in decreased heart rate while exposure of only the CNS resulted in an increase in heart rate. These observations suggest that the increase in heart rate that is observed in intact air-dehydrated slugs is primarily mediated by the CNS.     

Phagocytosis of degenerating myelin in transected feline optic nerve: an immunohistochemical study

The phagocytic activity of neuroglial cells in adult feline degenerating optic nerve was investigated by immunocytochemistry at both light and electron microscopy levels. Degeneration was initiated by unilateral eye enucleation and the segment distal to the transection showing true Wallerian degeneration was examined. Following enucleation, twelve adult domestic cats were examined over a period of seven to 215 days. All cases showed slow clearance of myelin debris and absence of proliferating monocytes throughout the post-enucleation period. All phagocytic cells present were neuroglial cells, and many of these cells expressed oligodendroglial antigens. These findings demonstrate the persistence of an active population of oligodendrocytes that might play an additional functional role during Wallerian degeneration of feline optic nerve.     

Primate Location Preference in a Double-Tier Cage: The Effects of Illumination and Cage Height

Nonhuman primates are frequently housed in double-tier arrangements with significant differences between the environments of the upper and lower-row cages. Although several studies have investigated whether this arrangement alters monkeys' behavior, no studies have addressed the two most notable differences, light and height, individually to determine their relative importance. This experiment examined how rhesus and long-tailed macaques allocated their time between the upper and lower-row cages of a 1-over-1 apartment module under different lighting conditions. In Condition A, monkeys' baseline degree of preference for the upper- and lower-row was tested. In Condition B, the lighting environment was reversed by limiting illumination in the upper-row cage and increasing illumination in the lower-row cage. In both conditions, monkeys spent more time in the upper-row cage, thus indicating a strong preference for elevation regardless of illumination. The amount of time that monkeys spent in the lower-row cage increased by 7% under reversed lighting, but this trend was not significant. These results corroborate the importance of providing captive primates with access to elevated areas.     

Anthocyanins: Structural characteristics that result in unique metabolic patterns and biological activities

Interest in anthocyanins has increased immensely during the past decade. From these studies, it is clear that anthocyanins have unique properties: Anthocyanins are absorbed intact and absorption can be saturated; acylation of anthocyanins lowers their apparent absorption; anthocyanidin diglycosides in the form of sambubioside or rutinoside impart increased stability to the anthocyanin molecule; and the quantities excreted in urine are less than 0.1% of intake. However, 60–90% of the anthocyanins may disappear from the gastrointestinal tract within 4 h after a meal. What happens to the bulk of the anthocyanins that disappear is not clear. Degradation accounts for a part of this disappearance, but differs for the various aglycones and may be modified further by the nature of the aglycone glycosylation, which further complicates our understanding of this process. Anthocyanins may play an important role in health promotion in terms of obesity prevention, cardiovascular health, anti-inflammatory and anti-cancer effects.     

Decreased reticuloendothelial system clearance and increased blood half-life and immune cell labeling for nano- and micron-sized superparamagnetic iron-oxide particles upon pre-treatment with Intralipid

Background

Superparamagnetic iron-oxide nanoparticles are useful as contrast agents for anatomical, functional and cellular MRI, drug delivery agents, and diagnostic biosensors. Nanoparticles are generally cleared by the reticuloendothelial system (RES), in particular taken up by Kupffer cells in the liver, limiting particle bioavailability and in-vivo applications. Strategies that decrease the RES clearance and prolong the circulation residence time of particles can improve the in-vivo targeting efficiency.

Methods

Intralipid 20.0%, an FDA approved nutritional supplement, was intravenously administered in rats at the clinical dose (2 g/kg) 1 h before intravenous injection of ultra-small superparamagnetic iron-oxide (USPIO) or micron-sized paramagnetic iron-oxide (MPIO) particles. Blood half-life, monocyte labeling efficiency, and particle biodistribution were assessed by magnetic resonance relaxometry, flow cytometry, inductively-coupled plasma MS, and histology.

Results

Pre-treatment with Intralipid resulted in a 3.1-fold increase in USPIO blood half-life and a 2-fold increase in USPIO-labeled monocytes. A 2.5-fold increase in MPIO blood half-life and a 5-fold increase in MPIO-labeled monocytes were observed following Intralipid pre-treatment, with a 3.2-fold increase in mean iron content up to 2.60 pg Fe/monocyte. With Intralipid, there was a 49.2% and 45.1% reduction in liver uptake vs. untreated controls at 48 h for USPIO and MPIO, respectively.

Conclusions

Intralipid pre-treatment significantly decreases initial RES uptake and increases in-vivo circulation and blood monocyte labeling efficiency for nano- and micron-sized superparamagnetic iron-oxide particles.

General significance

Our findings can have broad applications for imaging and drug delivery applications, increasing the bioavailability of nano- and micron-sized particles for target sites other than the liver.     

Genetic mapping of a major dominant gene for resistance to Ralstonia solanacearum in eggplant

Resistance of eggplant against Ralstonia solanacearum phylotype I strains was assessed in a F₆ population of recombinant inbred lines (RILs) derived from a intra-specific cross between S. melongena MM738 (susceptible) and AG91-25 (resistant). Resistance traits were determined as disease score, percentage of wilted plants, and stem-based bacterial colonization index, as assessed in greenhouse experiments conducted in Réunion Island, France. The AG91-25 resistance was highly efficient toward strains CMR134, PSS366 and GMI1000, but only partial toward the highly virulent strain PSS4. The partial resistance found against PSS4 was overcome under high inoculation pressure, with heritability estimates from 0.28 to 0.53, depending on the traits and season. A genetic map was built with 119 AFLP, SSR and SRAP markers positioned on 18 linkage groups (LG), for a total length of 884 cM, and used for quantitative trait loci (QTL) analysis. A major dominant gene, named ERs1, controlled the resistance to strains CMR134, PSS366, and GMI1000. Against strain PSS4, this gene was not detected, but a significant QTL involved in delay of disease progress was detected on another LG. The possible use of the major resistance gene ERs1 in marker-assisted selection and the prospects offered for academic studies of a possible gene for gene system controlling resistance to bacterial wilt in solanaceous plants are discussed.     

Sex Specific Differences in Fetal Middle Cerebral Artery and Umbilical Venous Doppler

Background

The incidence of several adverse pregnancy outcomes including fetal growth restriction are higher in pregnancies where the fetus is male, leading to suggestions that placental insufficiency is more common in these fetuses. Placental insufficiency associated with fetal growth restriction may be identified by multi-vessel Doppler assessment, but little evidence exists regarding sex specific differences in these Doppler indices or placental function. This study aims to investigate sex specific differences in fetal and placental perfusion and to correlate these changes with intra-partum outcome.

Methods and Findings

This is a prospective cohort study. We measured Doppler indices of 388 term pregnancies immediately prior to the onset of active labour (≤3 cm dilatation). Fetal sex was unknown at the time of the ultrasound assessment. Information from the ultrasound scan was not made available to clinical staff. Case notes and electronic records were reviewed following delivery. We report significantly lower Middle Cerebral artery pulsatility index (1.34 vs. 1.43, p = 0.004), Middle Cerebral artery peak velocity (53.47 cm/s vs. 58.10 cm/s, p = <0.001), and Umbilical venous flow/kg (56 ml/min/kg vs. 61 ml/min/kg, p = 0.02) in male fetuses. These differences however, were not associated with significant differences in intra-partum outcome.

Conclusion

Sex specific differences in feto-placental perfusion indices exist. Whilst the physiological relevance of these is currently unknown, the identification of these differences adds to our knowledge of the physiology of male and female fetuses in utero. A number of disease processes have now been shown to have an association with changes in fetal haemodynamics in-utero, as well as having a sex bias, making further investigation of the sex specific differences present during fetal life important. Whilst the clinical application of these findings is currently limited, the results from this study do provide further insight into the gender specific circulatory differences present in the fetal period.