Fatty acid composition in adductor muscle of juvenile scallops (Pecten maximus) from five Norwegian populations reared in the same environment

Adductor muscle fatty acid (FA) composition was compared in Pecten maximus juveniles originating from five locations along the Norwegian coast from 59°N to 65°N to detect possible population differences. Broodstock sized scallops were translocated to sea conditions by a scallop hatchery near Bergen (60°N) before spawning in February 2006. The scallop larvae and juveniles were reared in the same environment for two years and 10 individuals from each population were sampled in May 2007 and in May 2008 for analysis of the FAs in the adductor muscle. The total lipid content determined as total amount of FAs were 5.7 ± 0.3 mg per g tissue, and no significant difference was found among the five populations. The polyunsaturated FAs made up close to 60% of the total, with 20:5n3 and 22:6n3 dominating. The saturated FA content was approximately 30%, while the monounsaturated FA were less abundant (7–10%). The FA composition of the muscles of the five populations was similar within each year, with larger differences between the years. Multivariate, supervised learning method PLS, applied pairwise, showed distinct FA composition, between the scallops from the five locations, indicating population differences. The relatedness between the populations was different in the two years, but the distinct FA profiles of the adductor muscle could be used to distinguish between scallop populations on a local scale. The results indicate habitat-specific lipid metabolism which may have important implications for the scallop aquaculture industry in the context of producing well adapted individuals for the specific locations.     

Testing candidate genes for attention-deficit/hyperactivity disorder in fruit flies using a high throughput assay for complex behavior

Fruit flies are important model organisms for functional testing of candidate genes in multiple disciplines, including the study of human diseases. Here we use a high-throughput locomotor activity assay to test the response on activity behavior of gene disruption in Drosophila melanogaster. The aim was to investigate the impact of disruption of 14 candidate genes for human attention-deficit/hyperactivity disorder (ADHD) on fly behavior. By obtaining a range of correlated measures describing the space of variables for behavioral activity we show, that some mutants display similar phenotypic responses, and furthermore, that the genes disrupted in those mutants had common molecular functions; namely processes related to cGMP activity, cation channels and serotonin receptors. All but one of the candidate genes resulted in aberrant behavioral activity, suggesting involvement of these genes in behavioral activity in fruit flies. Results provide additional support for the investigated genes being risk candidate genes for ADHD in humans.     

Essential role of insulin and insulin-like growth factor 1 receptor signaling in cardiac development and function

Cardiovascular disease is the leading cause of death in people with type 2 diabetes and is linked to insulin resistance even in the absence of diabetes. Here we show that mice with combined deficiency of the insulin receptor and insulin-like growth factor 1 (IGF-1) receptor in cardiac and skeletal muscle develop early-onset dilated cardiomyopathy and die from heart failure within the first month of life despite having a normal glucose homeostasis. Mice lacking the insulin receptor show impaired cardiac performance at 6 months, and mice lacking the insulin receptor plus one Igf1r allele have slightly increased mortality. By contrast, mice lacking the IGF-1 receptor or the IGF-1 receptor plus one Ir allele appear normal. Morphological characterization and oligonucleotide array analysis of gene expression demonstrate that prior to development of these physiological defects, mice with combined deficiency of both insulin and IGF-1 receptors have a coordinated down-regulation of genes encoding components of the electron transport chain and mitochondrial fatty acid beta-oxidation pathways and altered expression of contractile proteins. Thus, while neither the insulin receptor nor IGF-1 receptor in muscle is critical for glucose homeostasis during the first month of life, signaling from these receptors, particularly the insulin receptor, is required for normal cardiac metabolism and function.     

Rad18 E3 ubiquitin ligase activity mediates Fanconi anemia pathway activation and cell survival following DNA topoisomerase 1 inhibition

Camptothecin (CPT) and related chemotherapeutic drugs induce formation of DNA topoisomerase I (Top1) covalent or cleavage complexes (Top1ccs) that block leading-strand DNA synthesis and elicit DNA Double Stranded Breaks (DSB) during S phase. The Fanconi Anemia (FA) pathway is implicated in tolerance of CPT-induced DNA damage yet the mechanism of FA pathway activation by Top1 poisons has not been studied. We show here that the FA core complex protein FANCA and monoubiquitinated FANCD2 (an effector of the FA pathway) are rapidly mobilized to chromatin in response to CPT treatment in several human cancer cell lines and untransformed primary human dermal fibroblasts. FANCD2 depletion using siRNA leads to impaired recovery from CPT-induced inhibition or DNA synthesis, persistence of γH2AX (a DSB marker) and reduced cell survival following CPT treatment. The E3 ubiquitin ligase Rad18 is necessary for CPT-induced recruitment of FANCA and FANCD2 to chromatin. Moreover, Rad18-depletion recapitulates the DNA synthesis and survival defects of FANCD2-deficiency in CPT-treated cells. It is well-established that Rad18 promotes FA pathway activation and DNA damage tolerance in response to bulky DNA lesions via a mechanism involving PCNA monoubiquitination. In contrast, PCNA monoubiquitination is not involved in Rad18-mediated FA pathway activation or cell survival following acquisition of CPT-induced DSB. Moreover, while Rad18 is implicated in recombinational repair of DSB via an E3 ligase-independent mechanism, we demonstrate that Rad18 E3 ligase activity is essential for appropriate FA pathway activation and DNA damage tolerance after CPT treatment. Taken together, our results define a novel pathway of Rad18-dependent DSB repair that is dissociable from known Rad18-mediated DNA repair mechanisms based on its independence from PCNA ubiquitination and requirement for E3 ligase activity.Key words: camptothecin, Rad18, topoisomerase I, double strand breaks, Fanconi anemia     

Building‐Site Camps and Extended Work Hours: A Two‐Week Monitoring of Self‐Reported Physical Exertion,Fatigue, and Daytime Sleepiness

Large‐scale construction work often requires people to work longer daily hours and more than the ordinary five days in a row. In order to minimize transportation times and optimize the use of personnel, workers are sometimes asked to live in temporary building‐site camps in the proximity of the work site. However, little is known about the biological and psychological effects of this experience. The objective of the present study was to investigate whether exposure to long work hours and extended workweeks while living in building‐site camps in between work shifts was associated with a build‐up of increased complaints of poor sleep, daytime sleepiness, physical exertion, and fatigue across a two‐week work cycle. Two groups of construction workers were examined. The camp group of 13 participants (mean age: 42±11 S.D. yrs) lived in building‐site camps and worked extended hours (between 07:00 and 18:00 h) and extended workweeks (six days in a row, one day off, five days in a row, nine days off). The home group of 16 participants (mean age 40±9 yrs) worked ordinary hours between 07:00 and 15:00 h and returned home after each workday. Self‐ratings of daytime sleepiness (Karolinska Sleepiness Scale), physical exertion (Borg CR‐10), and mood were obtained six or seven times daily during two workweeks. Fatigue ratings were obtained once daily in the evening, and ratings of sleep disturbances were obtained once daily in the morning with the Karolinska Sleep Diary. Data were evaluated in a repeated measures design. The results showed that both groups reported a similar level of daytime sleepiness, physical exertion, and mood across workdays and time points within a workday (all three‐way interactions had p>0.898). Although the home group reported earlier wake‐up times, the pattern of sleep disturbance ratings across the workdays did not differ between the groups. Both groups reported few sleep disturbances and good mood. However, the camp group reported higher physical exertion already at the start of work and showed a more gentle increase in ratings during the work shift and a smaller decline between the end of work and bedtime. The camp group also reported higher fatigue scores than the home group. However, none of the groups showed signs of increasing ratings in the progress of the two workweeks. For both groups, the ratings of daytime sleepiness formed a U‐shaped pattern, with the highest scores at awakening and at bedtime. Yet, the camp group reported higher daytime sleepiness than the home group at lunch break and at the second break in the afternoon. In conclusion, there were no signs of fatigue build‐up or accumulation of daytime sleepiness, physical exertion, or sleep disturbances in either group. Despite the fact that the camp group showed some signs of having trouble in recuperating in between work shifts, as indicated by the higher physical exertion ratings at the start of work, higher fatigue scores, and higher daytime sleepiness, the results constitute no real foundation for altering the camp group's current work schedule and living arrangements.     

Evidence for a voltage-gated, non-selective cation channel in the human red cell membrane.

Using the patch clamp technique we have identified a voltage-dependent, non-selective cation channel in the human red cell membrane. Basic properties of this channel are reported, and it is proposed that it may be involved in the increased transport of cations which is seen when intact human red cells are suspended in a depolarising media.     

Isethionate in certain red algae

Isethionic acid (2-hydroxyethanesulfonic acid) was isolated as salts from a methanolic extract ofHypnea musciformis collected in the Indian Ocean and identified by comparison (nuclear magnetic resonance, infrared and mass spectrometry) with an authentic sample. The compound has not previously been reported from plants. Investigations of 13 other species of red algae showed that only some samples of species of the families Gigartinaceae, Hypnaceae and Solieriaceae (all of order Gigartinales) contained isethionates.Author for correspondence     

Non-amidated forms of VIP (glycine-extended VIP and VIP-free acid) have full bioactivity on smooth muscle

The aim of the present study was to elucidate the importance of the C-terminal amide group for the biological activity of vasoactive intestinal peptide (VIP). Two synthetic peptides lacking the amide group: VIP having a carboxyl group at the C-terminus and the intermediate biosynthetic precursor, glycine-extended VIP were compared with VIP itself regarding the ability to inhibit spontaneous activity in smooth muscle strips from rat stomach and human Fallopian tube. Both the glycine-extended VIP and VIP having a carboxyl group at the C-terminus caused a significant and dose-dependent inhibition of smooth muscle activity and displayed dose-response curves similar to VIP. The potencies of the VIP variants did not differ significantly from that of VIP. Thus, alpha-carboxyamidation of VIP is not a prerequisite for biological activity.     

Peptide histidine methionine (PHM) increases vaginal blood flow in normal women

The effect of increasing doses of PHM given subepithelially or intravenously on vaginal blood flow was studied. Vaginal blood flow was measured by a heated oxygen electrode, and the concentration of PHM in peripheral plasma was monitored radioimmunochemically. Injection of PHM induced a significant dose-dependent increase in vaginal blood flow. The flow values correlated with the plasma concentrations independent of the way of administration. The efficacy was the same as previously found for VIP but the potency of subepithelially injected PHM was found to be 10-fold lower than that of VIP. In conclusion, PHM and VIP seem to have similar vasodilatory effects upon vaginal blood flow.