Which alkylglycerols from shark liver oil have anti-tumour activities?

Alkylglycerols (alkyl-Gro) are ether lipids abundant in shark liver oil (SLO), and oral SLO or alkyl-Gro mix from this source have several in vivo biological activities including stimulation of haematopoiesis an immunological defences, or anti-tumour and anti-metastasis activities in vivo. Composition of natural alkyl-Gro mix contains several alkyl-Gro varying by chain length and unsaturation, and individual anti-tumour activity of each molecule present in natural mix remained unknown. We synthesized six prominent constituents of natural alkyl-Gro mix, namely 12:0, 14:0 16:0, 18:0, 16:1 n-7, and 18:1 n-9 alkyl-Gro. Using an in vivo model of grafted tumour in mice (3LL cells), we studied and compared the oral anti-tumour and anti-metastasis activities of each of these 6 alkyl-Gro. 16:1 and 18:1 alkyl-Gro showed strong activity in reducing lung metastasis number, while saturated alkyl-Gro had weaker (16:0) or no (12:0, 14:0, 18:0) effect. Spleen weights at day 20 after graft were also measured and showed tremendous variations depending on the treatment. Tumour graft resulted in a raise in spleen weight in control group, this raise was nearly abolished in 16:1 and 18:1 alkyl-Gro-treated mice, and was reduced in 14:0 and 16:0 alkyl-Gro-treated mice. Conversely, 18:0 alkyl-Gro-treated mice showed spleen weigh raise as compared with untreated grafted mice. These new data demonstrate a prominent role of unsaturation in the anti-tumour activities of alkyl-Gro.     

Impairment of proteasome function upon UVA- and UVB-irradiation of human keratinocytes

The major environmental influence for epidermal cells is sun exposure and the harmful effect of UV radiation on skin is related to the generation of reactive oxygen species that are altering cellular components including proteins. It is now well established that the proteasome is responsible for the degradation of oxidized proteins. Therefore, the effects of UV-irradiation on proteasome have been investigated in human keratinocyte cultures. Human keratinocytes were irradiated with 10 J/cm(2) of UVA and 0.05 J/cm(2) of UVB and proteasome peptidase activities were measured in cell lysates using fluorogenic peptides. All three peptidase activities were decreased as early as 1 h and up to 24 h after irradiation of the cells. Increased levels of oxidized and ubiquitinated proteins as well as proteins modified by the lipid peroxidation product 4-hydroxy-2-nonenal were also observed in irradiated cells. However, immunopurified 20S proteasome exhibited no difference in both peptidase specific activities and 2D gel pattern of subunits in irradiated cells, ruling out the possibility that the 20S proteasome could be a target for the UV-induced damage. Finally, extracts from irradiated keratinocytes were able to inhibit degradation by the proteasome, demonstrating the presence of endogeneous inhibitors, including 4-hydroxy-2-nonenal modified proteins, generated upon UV-irradiation.     

Nectar robbing improves male reproductive success of the endangered Aconitum napellus ssp. lusitanicum

Nectar robbery is usually thought to impact negatively on the reproductive success of plants, but also neutral or even positive effects have been reported. Very few studies have investigated the effects of nectar robbing on the behaviour of legitimate pollinators so far. Such behavioural changes may lead to the reduction of geitonogamy or to increased pollen movement. We simulated nectar robbing in experimental sites as well as in natural populations of Aconitum napellus ssp. lusitanicum, a rare plant pollinated by long-tongued bumblebees. In an experimental setup, we removed the nectaries of 40 % of the flowers, which is similar to rates of robbing observed in wild populations. Patches of plants with experimentally robbed flowers were compared with control patches containing plants with untreated flowers. We observed pollinator behaviour, mimicked male reproductive success (pollen dispersal) using fluorescent dye, and measured female reproductive success (seed set). The main legitimate visitors were bumblebees while honeybees were often observed robbing nectar. They did so by “base working”, i.e. sliding between tepals. Bumblebees tended to visit fewer flowers per plant and spent less time per single flower when these had been experimentally robbed. This change in behaviour consequently increased the proportion of flowers visited by bumblebees in patches with robbed flowers. Fluorescent dye mimicking pollen flow was dispersed larger distances after pollinators had visited patches with robbed flowers compared to control patches. Average seed set per plant was not affected by nectar robbing. Our results demonstrated that A. napellus does not suffer from nectar robbery but may rather benefit via improved pollen dispersal and thus, male reproductive success. Knowledge on such combined effects of behavioural changes of pollinators due to nectar robbery is important to understand the evolutionary significance of exploiters of such mutualistic relationships between plants and their pollinators.     

Molecular characterization and analysis of the operon encoding the antifungal lipopeptide bacillomycin D

Bacillus subtilis AU195 produces bacillomycin D, a cyclic lipopeptide that is an inhibitor of the aflatoxin producing fungus Aspergillus flavus. Sequence analysis of the bacillomycin D operon revealed four ORFs with the structural organization of the peptide synthetases. Disruption of ORF 2, which links the amino acid moiety to the b-amino fatty acid, resulted in the loss of antifungal activity. By comparing the sequence of bacillomycin D, iturin A and mycosubtilin operons, our results showed that intergenic module replacement have occurred between B. subtilis lipopeptide synthetases including the iturin family and the plipastatin and fengycin family.     

Selfing inNarthecium ossifragum (Melanthiaceae)

Hagerup's (1950) observations of rain pollination inNarthecium ossifragum are commonly admitted. Nevertheless,Daumann (1970) stated that pollen and stigmas suffer considerable damage from rain impact. Experimental pollinations and pollen observations were conducted at a single site in the Upper Ardennes, Belgium, during three years. Rain water had a deleterious effect on both fruit and seed set and on pollen germination. Fruit and seed set differed among years mainly due to rainy weather. Fruit set also varied among experimental treatments. Pollination trials showed thatNarthecium ossifragum is self-compatible and autofertile. Emasculation had a deleterious effect and caging had no effect on fertility.     

Impact of Monochorionicity and Twin to Twin Transfusion Syndrome on Prenatal Attachment,Post Traumatic Stress Disorder,Anxiety and Depressive Symptoms

Monochronioric (MC) twin pregnancies are considered as high-risk pregnancies with potential complications requiring in-utero interventions. We aimed to assess prenatal attachment, anxiety, post-traumatic stress disorder (PTSD) and depressive symptoms in MC pregnancies complicated with Twin-To-Twin-transfusion syndrome (TTTS) in comparison to uncomplicated monochorionic (UMC) and dichorionic pregnancies (DC). Auto-questionnaires were filled out at diagnosis of TTTS and at successive milestones. Prenatal attachment, PTSD, anxiety and perinatal depression were evaluated respectively by the Prenatal Attachment Inventory (PAI) completed for each twin, the Post-traumatic Checklist Scale (PCLS), the State-Trait Anxiety Inventory (STAI) and the Edinburgh Perinatal Depression Scale (EPDS). There was no significant difference in the PAI scores between the two twins. In the DC and UMC groups, PAI scores increased throughout pregnancy, whilst it didn’t for TTTS group. TTTS and DC had a similar prenatal attachment while MC mothers expressed a significantly higher attachment to their fetuses and expressed it earlier. At the announcement of TTTS, 72% of the patients present a score over the threshold at the EPDS Scale, with a higher score for TTTS than for DC (p = 0.005), and UMC (p = 0.007) at the same GA. 30% of mothers in TTTS group have PTSD during pregnancy. 50% of TTTS- patients present an anxiety score over the threshold (STAI-Scale), with a score significantly higher in TTTS than in UMC (p<0.001) or DC (p<0.001). The proportion of subject with a STAI–State over the threshold is also significantly higher in TTTS than in DC at 20 GW (p = 0.01) and at 26 GW (p<0.05). The STAI-state scores in UMC and DC increase progressively during pregnancy while they decrease significantly in TTTS. TTTS announcement constitutes a traumatic event during a pregnancy with an important risk of PTSD, high level of anxiety and an alteration of the prenatal attachment. These results should guide the psychological support provided to these patients.     

Resveratrol Improved Flow-Mediated Outward Arterial Remodeling in Ovariectomized Rats with Hypertrophic Effect at High Dose

Objectives

Chronic increases in blood flow in resistance arteries induce outward remodeling associated with increased wall thickness and endothelium-mediated dilatation. This remodeling is essential for collateral arteries growth following occlusion of a large artery. As estrogens have a major role in this remodeling, we hypothesized that resveratrol, described as possessing phytoestrogen properties, could improve remodeling in ovariectomized rats.

Methods

Blood flow was increased in vivo in mesenteric arteries after ligation of adjacent arteries in 3-month old ovariectomized rats treated with resveratrol (5 or 37.5 mg/kg per day: RESV5 or RESV37.5) or vehicle. After 2 weeks arterial structure and function were measured in vitro in high flow (HF) and normal flow (NF) arteries isolated from each rat.

Results

Arterial diameter was greater in HF than in NF arteries in ovariectomized rats treated with RESV5 or RESV37.5, not in vehicle-treated rats. In mice lacking estrogen receptor alpha diameter was equivalent in HF and NF arteries whereas in mice treated with RESV5 diameter was greater in HF than in NF vessels. A compensatory increase in wall thickness and a greater phenylephrine-mediated contraction were observed in HF arteries. This was more pronounced in HF arteries from RESV37.5-treated rats. ERK1/2 phosphorylation, involved in hypertrophy and contraction, were higher in RESV37.5-treated rats than in RESV5- and vehicle-treated rats. Endothelium-dependent relaxation was greater in HF than in NF arteries in RESV5-treated rats only. In HF arteries from RESV37.5-treated rats relaxation was increased by superoxide reduction and markers of oxidative stress (p67phox, GP91phox) were higher than in the 2 other groups.

Conclusion

Resveratrol improved flow-mediated outward remodeling in ovariectomized rats thus providing a potential therapeutic tool in menopause-associated ischemic disorders. This effect seems independent of the estrogen receptor alpha. Nevertheless, caution should be taken with high doses inducing excessive contractility and hypertrophy in association with oxidative stress in HF arteries.