University of Sussex

New research identifies protein (PANK4) as an obstacle that blocks cancer cells from responding to chemotherapeutic treatment for glioblastoma. New research by the University of Sussex could help to increase life expectancy and improve treatment for an aggressive brain cancer, which impacts thousands of people every year in the UK, and hundreds of thousands worldwide. In the study, published in the journal of Advanced Science, researchers have discovered that an understudied protein, called PANK4, is able to block cancer cells from responding to chemotherapeutic treatment for the highly intrusive brain cancer, glioblastoma. Scientists at Sussex have demonstrated that if the protein is removed, cancer cells respond better to the main chemotherapy drug used globally for the treatment of glioblastoma. Prof Georgios Giamas, Professor of Cancer Cell Signalling at the University of Sussex explains: "Glioblastoma is a devastating brain cancer, and researchers are working hard to identify ways to delay progression of the disease, and tackle cell resistance to treatment. As this is the first time that PANK4 has been linked to glioblastoma, the next step is to develop a drug targeting this protein to try to reverse chemo-resistance and restore sensitivity, ensuring that patients receive the best treatment and have better outcomes." Glioblastoma is one of the most aggressive forms of brain cancer. Approximately 3,200 adults are diagnosed with the disease each year in the UK, and around 250,000 -- 300,000 globally, with a best-case survival rate of just one to 18 months after diagnosis. Following surgery to remove the tumour, glioblastoma patients are typically treated with radiation and the chemotherapeutic drug, temozolomide. Although patients initially respond well to the drug, the cancer cells quickly develop resistance to this treatment. The University of Sussex scientists led an international research team to understand the possible reasons for this resistance, helping to guide future therapies to improve quality of life and increase life expectancy for those with glioblastoma. The team identified a protein called PANK4 which, when removed from the cancer cells, can lead to the cell's death, and saw patients better responding to temozolomide. Linked to this, the researchers found that patients expressing high levels of the PANK4 protein had lower survival rates. Dr Viviana Vella, research fellow at the University of Sussex explains: "There are a multitude of under-investigated proteins that may hold great potential for therapeutic intervention. Our study sheds light on this understudied protein, PANK4, unveiling a protective role in temozolomide-resistant cancer cells. Ultimately, PANK4 depletion represents a vulnerability that can now be exploited to restore sensitivity to the drug and improve treatment." This study contributes to a body of ground-breaking research from the Sussex researchers, which focuses on the early diagnosis and treatment of glioblastoma. The research group now hope to develop a drug to reverse chemo-resistance and improve outlook for patients. Ms Charley Cranmer, Director of Fundraising and Communications, Action Against Cancer who funded the research adds: "Action Against Cancer is very proud to have funded this ground-breaking research that offers such hope for patients with this type of aggressive brain cancer."

Scientists have found the strongest evidence yet that our brains can compensate for age-related deterioration by recruiting other areas to help with brain function and maintain cognitive performance. Scientists have found the strongest evidence yet that our brains can compensate for age-related deterioration by recruiting other areas to help with brain function and maintain cognitive performance. As we age, our brain gradually atrophies, losing nerve cells and connections and this can lead to a decline in brain function. It's not fully understood why some people appear to maintain better brain function than others, and how we can protect ourselves from cognitive decline. A widely accepted notion is that some people's brains are able to compensate for the deterioration in brain tissue by recruiting other areas of the brain to help perform tasks. While brain imaging studies have shown that the brain does recruit other areas, until now it has not been clear whether this makes any difference to performance on a task, or whether it provides any additional information about how to perform that task. In a study published in the journal eLife, a team led by scientists at the University of Cambridge in collaboration with the University of Sussex have shown that when the brain recruits other areas, it improves performance specifically in the brains of older people. Study lead Dr Kamen Tsvetanov, an Alzheimer's Society Dementia Research Leader Fellow in the Department of Clinical Neurosciences, University of Cambridge, said: "Our ability to solve abstract problems is a sign of so-called 'fluid intelligence', but as we get older, this ability begins to show significant decline. Some people manage to maintain this ability better than others. We wanted to ask why that was the case -- are they able to recruit other areas of the brain to overcome changes in the brain that would otherwise be detrimental?" Brain imaging studies have shown that fluid intelligence tasks engage the 'multiple demand network' (MDN), a brain network involving regions both at the front and rear of the brain, but its activity decreases with age. To see whether the brain compensated for this decrease in activity, the Cambridge team looked at imaging data from 223 adults between 19 and 87 years of age who had been recruited by the Cambridge Centre for Ageing & Neuroscience (Cam-CAN). The volunteers were asked to identify the odd-one-out in a series of puzzles of varying difficulty while lying in a functional magnetic resonance imaging (fMRI) scanner, so that the researchers could look at patterns of brain activity by measuring changes in blood flow. As anticipated, in general the ability to solve the problems decreased with age. The MDN was particularly active, as were regions of the brain involved in processing visual information. When the team analysed the images further using machine-learning, they found two areas of the brain that showed greater activity in the brains of older people, and also correlated with better performance on the task. These areas were the cuneus, at the rear of the brain, and a region in the frontal cortex. But of the two, only activity in the cuneus region was related to performance of the task more strongly in the older than younger volunteers, and contained extra information about the task beyond the MDN. Although it is not clear exactly why the cuneus should be recruited for this task, the researchers point out that this brain region is usually good at helping us stay focused on what we see. Older adults often have a harder time briefly remembering information that they have just seen, like the complex puzzle pieces used in the task. The increased activity in the cuneus might reflect a change in how often older adults look at these pieces, as a strategy to make up for their poorer visual memory. Dr Ethan Knights from the Medical Research Council Cognition and Brain Sciences Unit at Cambridge said: "Now that we've seen this compensation happening, we can start to ask questions about why it happens for some older people, but not others, and in some tasks, but not others. Is there something special about these people -- their education or lifestyle, for example -- and if so, is there a way we can intervene to help others see similar benefits?" Dr Alexa Morcom from the University of Sussex's School of Psychology and Sussex Neuroscience research centre said: "This new finding also hints that compensation in later life does not rely on the multiple demand network as previously assumed, but recruits areas whose function is preserved in ageing." The research was supported by the Medical Research Council, the Biotechnology and Biological Sciences Research Council, the European Union's Horizon 2020 research and innovation programme, the Guarantors of Brain, and the Alzheimer's Society.

New research fueled in part by citizen scientists reveals that the meadow spittlebug—known for the foamy, spit-like urine released by its nymphs—can feed on at least 1,300 species of host plants, more than twice the number of any other insect. New research fueled in part by citizen scientists reveals that the meadow spittlebug -- known for the foamy, spit-like urine released by its nymphs -- can feed on at least 1,300 species of host plants, more than twice the number of any other insect. The study, which is published today in the journal PLOS ONE, could be especially important in the effort to stop the bug from spreading a type of bacterium that has caused the death of crops across the world, including olive trees in Italy, grapevines in California, citrus trees in South America, and almond trees in Spain. "Thirteen hundred host plants means 1,300 opportunities to spread pathogenic bacteria in natural and agricultural environments, a sobering wake-up call," said the study's lead author Vinton Thompson, a research associate in the Museum's Division of Invertebrate Zoology. Meadow spittlebugs (Philaenus spumarius), also called froghoppers, suck sap from plants with straw-like mouthparts, picking up bacteria along the way and becoming vectors for plant diseases. Most recently, the bugs have been found to spread the bacterium Xylella fastidiosa, a pathogen that has decimated olive groves in the Apulia region of Italy. To predict what other plant species and ecosystems are at risk, scientists must understand the vector's host range. Thompson, who has been studying and documenting host plants of spittlebugs for 50 years, set out to do that along with collaborators in the United Kingdom. The scientists combined data from published literature, host records associated with museum specimens, observations, and data from a citizen science effort carried out in Britain called BRIGIT, which ran from 2019-2021 to help prepare for the possible introduction of X. fastidiosa to the UK. Meadow spittlebugs have a wide geographical range and can thrive in drastically different climates, from Hawaii to just south of the Arctic Circle. Scientists have suspected for some time that this bug had more hosts than any other insect, but the number they calculated was startling: the meadow spittlebug feeds on more than 1,300 species of plants across 117 families -- a world record for insects. These plant species include ferns, herbs, shrubs, vines and trees, annuals and perennials, grasses and forbs, plants of the tropics, subtropics, temperate and boreal zones, and conifers. The researchers found that the insect with the second-highest number of plant hosts is the fall webworm, a moth that is known to feed on 636 different plant species. "The spittlebug is the ultimate herbivore champion," said study author Claire Harkin, from the University of Sussex. "It will feed on just about every imaginable kind of vascular plant except those submerged in aquatic environments." Why do meadow spittlebugs have so many more host plants? More research is needed, but the scientists suspect it's due to the bugs' preference for sap from the xylem, which is the main water-carrying structure of the plant. Most sap-eating bugs feed from the plant's phloem, which is the tissue that transmits sugar and other metabolic compounds. Unlike sap from the phloem, the liquid in the xylem is similar across a diverse range of host plants. "These bugs feed on almost anything they can get at with their mouth parts," Thompson said. "Unfortunately, that means there is tremendous potential for the spread of X. fastidiosa in natural ecosystems if it's introduced. This review is just the first step in thinking about how to control this bug and the diseases it spreads." The meadow spittlebug is no stranger to superlatives: it is the highest jumping insect proportional to body size and has the largest measured sucking power of any bug -- strong enough that it could suck the water out of a cup at the base of the Statue of Liberty while perched on its crown. It also is exceptional at urination, excreting the human equivalent of 2,500 gallons of urine a day.