Metastasis Suppressor microRNA-335 Targets the Formin Family of Actin Nucleators

MiRNAs can have pleiotropic effects by targeting multiple genes belonging to diverse signalling networks. Alternatively, miRNAs can enhance the potency of their cellular effects by targeting multiple genes within the same genetic pathway. Previously, we and others have demonstrated that miR-335 is a potent suppressor of tumour cell migration, invasion and metastasis, in part by targeting several genes involved in these cellular processes, including ROCK1, MAPK1, LRG1, SP1 and SOX4. Here, we demonstrate that direct targeting of multiple members of the formin family of actin nucleators contributes to the inhibitory effects of miR-335 in neuroblastoma cells. We demonstrate that miR-335 regulates the expression of at least five formin family members and validate three family members, FMNL3, FMN2 and DAAM2, as direct targets of miR-335. The contribution of the formin family genes to cancer progression and metastasis has recently begun to emerge and here we demonstrate for the first time the ability of FMN2 and DAAM2 to regulate tumour cell migration and invasion, using siRNA-mediated inhibition of each of these formin genes. Finally, we demonstrate that the formin genes, in particular FMNL3, are responsible for the protrusion of actin-rich filopodia structures that contribute to the enhanced migratory and invasive potential associated with reduced expression of miR-335. Thus, direct targeting of the formin family contributes to the metastasis suppressing abilities of miR-335 by providing a direct regulatory link to the actin assembly machinery of the cell. We conclude that miR-335 is a master regulator of tumour cell migration and invasion by directly targeting a plethora of genes that effectively control cell migratory processes.     

A Comparison of the Energy Yield at the End User for M. x giganteus Using Two Different Harvesting and Transport Systems

A comparison between two different harvest systems for Miscanthus x giganteus crop (direct cut/chip and mow/bale) in terms of the net energy delivered to an end user, and the various energy costs and energy yields associated with each system was conducted. Only minor differences in terms of energy consumption were observed between the two harvest systems when all phases of the harvesting chain had been taken into account. Chip harvesting consumed 0.11 GJ?t^?1 compared with 0.13 GJ?t^?1 for bale harvesting. Chip transportation was considerably more expensive than bale transportation for a set distance of 50 km (0.18 and 0.11 GJ?t^?1 for chip and bale, respectively). Despite this, higher overall net energy yield was achieved by direct cutting and chipping the material. This was due to the higher proportion of harvestable energy lost in the field as a result of the use of a mowing/baling system. The overall net energy delivered in terms of harvestable material by the direct cut and chip system was 12.45 GJ?t^–1 compared with 11.78 GJ?t^?1 by the mow and bale system, making direct cut the more efficient system even up to a transport distance of 400 km. A sensitivity analysis indicated that the choice of transport system becomes more important for energy efficiency as transport distance increases.     

In-vivo response of the Human Uterus to Orciprenaline in Early Labour

The effect of orciprenaline on uterine activity in 10 women in early induced labour at term with intact membranes was studied. Nine had uterine contractions in response to intravenous oxytocin and one to prostaglandin E₂. The inhibition of uterine contractility was dose-dependent. The effective dose varied between 10 and 20 μg/minute. Tachyphylaxis was not observed. The only significant effects noted in the mother were tachycardia and increased pulse pressure and in the fetus a smaller increase in heart rate.     

Cloning and developmental expression of MARK/Par-1/MELK-related protein kinase xMAK-V in<Emphasis Type="Italic"> Xenopus laevis</Emphasis>

MAK-V/Hunk is a recently identified MARK/Par-1-related mammalian protein kinase. Although the precise function of this protein kinase is yet to be established, available data suggest its involvement in animals development and in the physiology of the nervous system. Here we report characterization of a cDNA encoding Xenopus laevis orthologue of MAK-V/Hunk protein kinase, xMAK-V. The in silico analysis also revealed MAK-V/Hunk orthologues in the fish Fugu rubripes and primitive chordate Ciona intestinalis but not in invertebrate species such as Drosophila melanogaster and Caenorhabditis elegans, suggesting that MAK-V/Hunk is a chordate-specific protein kinase. The expression of xmak-v in X. laevis embryos was analyzed using whole-mount in situ hybridization. Expression of xmak-v has been detected in all developmental stages studied including maternal expression in unfertilized eggs. The xmak-v mRNA has a predominant occurrence on the animal hemisphere of the egg, and this pattern of expression is sustained throughout cleavage and blastula stages. At the gastrula stage xmak-v expression is restricted to the ectoderm. In the later stage embryos xmak-v is expressed over the entire embryonic surface including the open neural plate at stage 15 and also in neural tube at stage 22. At tadpole stage xmak-v expression is strong in embryonic epidermis, nervous system and sensory organs, and is also obvious in perisomitic mesoderm and brachial arches.Edited by N. Satoh     

Vaginal Delivery under Caudal Analgesia after Caesarean Section and other Major Uterine Surgery

In the absence of a recurring indication for caesarean section vaginal delivery in subsequent pregnancy is a “trial of scar,” with potentially serious implications for mother and baby. Labour under caudal analgesia was carefully supervised for 75 women with a surgically scarred uterus—due to lower segment section in 72, abdominal hysterotomy in one, and transcavity myomectomy in two. Every caesarean scar was assessed digitally during labour and every uterus was examined after delivery. Caudal analgesia provided a painless labour and delivery and made scar assessment easy. Controlled intravenous Syntocinon infusion was given to 25 patients. One scar dehiscence occurred early in labour and one in the second stage. Seventy mothers had 71 vaginal deliveries with one pair of twins and one breech. There was one stillbirth and no neonatal death. There were five repeat sections.     

Amyloid fibril formation by lens crystallin proteins and its implications for cataract formation

The alpha-, beta-, and gamma-crystallins are the major structural proteins within the eye lens and are responsible for its exceptional stability and transparency. Under mildly denaturing conditions, all three types of bovine crystallin assemble into fibrillar structures in vitro. Characterization by transmission electron microscopy, dye binding assays, and x-ray fiber diffraction shows that these species have all of the characteristics of fibrils associated with the family of amyloid diseases. Moreover, the full-length proteins are incorporated into the fibrils, (i.e. no protein cleavage is required for these species to form), although for the gamma-crystallins some fragmentation occurs under the conditions employed in this study. Our findings indicate that the inherent stability of the beta-sheet supramolecular structure adopted by the crystallins in the eye lens and the chaperone ability of alpha-crystallin must be crucial for preventing fibril formation in vivo. The crystallins are very stable proteins but undergo extensive post-translational modification with age that leads to their destabilization. The ability of the crystallins to convert into fibrils under destabilizing conditions suggests that this process could contribute to the development of cataract with aging.