Source = e-Travel Blackboard: P.T NZ tour operator thl has announced plans to merge its New Zealand rental business with KEA Campers and United Campervans, in a bid to advocate tourism and deliver financial benefits. Although acquisition and implementation costs totalled $1.7 million, thl’s operating profit has been forecast rise to $19.3 million from $16.3 million during the 2012 financial year. “This merger is logical, strategic and the best response to the challenging realities of the current New Zealand market,” thl chairman Keith Smith said. “thl is the industry player that already has the scale to market New Zealand tourism and New Zealand campervan vacations to a broad international audience and therefore the best placed to make the most of the additional brands.” Debt reduction of $19 million is expected in the first eight months after the merger. In the first full year following the merger, operating earnings are forecast to rise to $28.8 million. “The merger is an appropriate response to the challenging macro-economic factors facing New Zealand tourism and the campervan industry,” thl chief executive Grant Webster said. United Campervans principal Kay Howe will join the thl board as an executive director to assist with the merger, while KEA Campers principal Grant Brady is poised to lead thl’s New Zealand vehicle sales operations. “thl, combined with United and KEA, has a great future and will be a powerful advocate for New Zealand tourism particularly in high-value international markets such as the United Kingdom and Europe,” Ms Howe said.thl recently posted high operating profits, despite global instability and economic uncertainty. The merger is scheduled to be completed on 31 October 2012.
Jul 27 2018A new drug discovery system allows scientists to specifically target members of an important family of enzymes, called phosphatases, which were previously considered mostly “undruggable”.Scientists from the Medical Research Council (MRC) Laboratory of Molecular Biology, in Cambridge, UK, demonstrated the capabilities of the new system by identifying a molecule that could successfully target a phosphatase to reduce the accumulation of Huntington’s disease-associated proteins in the brains of mice.The findings, published in Cell, could enable scientists to screen for drugs that can target specific phosphatases. Phosphatases are a type of enzyme that are a key part of signaling in cells – turning processes on and off. Most signaling starts with an activation signal – often when a type of enzyme called a kinase attaches a chemical tag, a phosphate group, to specific proteins to change their function. The signal is stopped by phosphatase enzymes, which cut off the phosphate group.There are more than 200 types of phosphatases involved in many different processes in cells, so any drug must selectively target only the right one, otherwise it will produce serious side-effects or kill the cell.Many drugs have been developed that can target specific kinases (such as anti-cancer drugs), but developing drugs that can specifically target particular phosphatases has proved difficult – because the functional part that cuts off phosphate groups is common to all phosphatases, so drugging one phosphatase inhibits hundreds of them and kills cells.Dr Anne Bertolotti from the MRC Laboratory of Molecular Biology, who led the study, said: “For decades, with no way to selectively target phosphatases, research into them has lagged behind kinases and they’ve been described as undruggable. Our new system is only a first step, but we hope cracking this problem will stimulate phosphatase research and drug development.”Targeting phosphatases – instead of kinases – is like targeting the brake, rather than the accelerator, on signals in cells. By inhibiting a phosphatase, we prolong a signaling event that has already been turned on, which may offer safer ways to specifically alter signaling in cells and help to create new drugs with fewer side-effects.”Related StoriesComputer-generated flu vaccine enters clinical trials in the USResearchers completely eliminate all traces of HIV from infected miceA Portable Solution for the On-scene Identification of KratomThe new system builds on previous work by the same scientists in which they created functional synthetic versions of phosphatase proteins.These synthetic phosphatases are tethered to chips so they can be screened to find a molecule that binds to one type of phosphatase, but to none of the other types. The successful molecule is then tested in cells grown in a dish to check it is safe before beginning testing in mice.Targeting Huntington’s diseaseThe researchers used the system to discover a molecule that showed promise in a mouse model of Huntington’s disease.Many neurodegenerative diseases, such as Alzheimer’s, Parkinson’s and Huntingdon’s diseases, feature misfolded proteins that accumulate in cells in the brain. The researchers hoped that slowing down a cell’s production of proteins could leave its ‘quality control machinery’ with more capacity to clear up the misfolded proteins.In this study, they aimed to slow down the cell’s protein production machinery by targeting a specific phosphatase (designated ‘PPP1R15B’). They used their new drug discovery platform and found a molecule, called Raphin1, that targeted only that phosphatase.When they tested Raphin1 in a mouse model of Huntington’s disease, they found it could cross into the brain where it reduced the accumulation of the disease-associated misfolded proteins in neurons. The scientists emphasize that this is early stage research and more work is needed to test if the drug will be safe or effective in humans.Dr Anne Bertolotti said: “Since Huntington’s disease runs in families and can be diagnosed genetically, early diagnosis could provide what we hope is a window of opportunity to target the disease before symptoms appear. Our unique approach manipulates cells to slow down normal functions and give them a chance to clear up the misfolded proteins that are characteristic of Huntington’s. However, it will take some years before we know if this approach works in humans and is safe.” Source:https://mrc.ukri.org/news/browse/drugs-to-target-undruggable-enzymes-critical-in-many-diseases/