University of Tromso

New research found that marine heat waves -- prolonged periods of unusually warm ocean temperatures -- haven't had a lasting effect on the fish communities that feed most of the world. The finding is in stark contrast to the devastating effects seen on other marine ecosystems cataloged by scientists after similar periods of warming, including widespread coral bleaching and harmful algal blooms. Rutgers-led research found that marine heat waves -- prolonged periods of unusually warm ocean temperatures -- haven't had a lasting effect on the fish communities that feed most of the world. The finding is in stark contrast to the devastating effects seen on other marine ecosystems cataloged by scientists after similar periods of warming, including widespread coral bleaching and harmful algal blooms. "There is an emerging sense that the oceans do have some resilience, and while they are changing in response to climate change, we don't see evidence that marine heat waves are wiping out fisheries," said Alexa Fredston, the lead author of the study who conducted the research as a postdoctoral associate in the Global Change Research Group, part of the Department of Ecology, Evolution and Natural Resources in the Rutgers School of Environmental and Biological Sciences (SEBS.) The study, published in Nature, assessed effects on commercially important fish such as flounder, pollock and rockfish based on data extracted from long-running scientific trawl surveys -- conducted by towing a net along the seafloor -- of continental shelf ecosystems in North America and Europe between 1993 and 2019. The analysis included 248 marine heat waves with extreme sea bottom temperatures during this period. The researchers were surprised to find that marine heat waves in general don't show major adverse effects on regional fish communities. Although declines in biomass did occur after some marine heat waves, the researchers said these cases were the exception, not the rule. Overall, they found that the effects of marine heat waves aren't distinguishable from the natural variability in these ecosystems. "The oceans are highly variable, and fish populations vary quite a lot," said Fredston, now an assistant professor of ocean sciences at University of California, Santa Cruz. "Marine heat waves can drive local change, but there have been hundreds of marine heat waves with no lasting impacts." In addition to assessing the impact on the total quantity of organisms in a given area, known as biomass, the researchers examined whether marine heat waves were causing changes in the variety of fish species composing fish communities. For example, evidence might show the loss of species associated with cold water and an increase in species associated with warm water, a phenomenon known as tropicalization. The findings suggest fish may be able to find safe havens by moving to areas with cooler water during marine heat waves, which the researchers defined as periods of more than five days with extreme sea bottom temperatures for that region and season. The data included some notable examples of marine heat waves that did have profound impacts, such as the 2014-2016 marine heat wave in the Northeast Pacific known as "the Blob," one of the largest on record. While "the Blob" led to a 22 percent loss of biomass in the Gulf of Alaska, a 2012 marine heat wave in the Northwest Atlantic led to a 70 percent biomass gain. The authors also noted that these weren't large changes compared to natural variability in biomass, and similar effects weren't seen after most other marine heat waves. "We found that these negative impacts are unpredictable and that other heat waves had no strong impacts," said Malin Pinsky, an associate professor in the Department of Ecology, Evolution and Natural Resources and director of the Global Change Research Group at SEBS and a co-author of the study. "This means that each heat wave that hits is like rolling the dice: Will it be a bad one or not? We don't know until it happens." Other Rutgers researchers who participated in the study include Zoë Kitchel, a doctoral student, and Aurore Maureaud, a postdoctoral associate, both with the Department of Ecology, Evolution and Natural Resources at SEBS. Researchers from other institutions participated in the study, including the University of British Columbia, the University of Bern in Switzerland, the National Oceanic and Atmospheric Administration, the French Research Institute for Exploitation of the Sea, the University of Montpellier in France, the University of Tromsø in Norway and Fisheries and Oceans Canada.

For the first time, researchers have succeeded in predicting how to change the optimum temperature of an enzyme using large computer calculations. A cold-adapted enzyme from an Antarctic bacterium was used as a basis. For the first time, researchers have succeeded in predicting how to change the optimum temperature of an enzyme using large computer calculations. A cold-adapted enzyme from an Antarctic bacterium was used as a basis. The study is to be published in the journal Science Advances and is a collaboration between researchers at Uppsala University and the University of Tromsø. The type of cold-adapted enzymes used by the researchers for their study can be found in bacteria and fish that live in icy water, for example. Evolution has shaped them to be able to function even at very low temperatures at which other enzymes are normally stone dead. These enzymes also always have a lower optimum temperature and melting point than enzymes from warm-blooded animals and organisms that live at higher temperatures. The researchers wondered whether computer simulations of the catalysed chemical reaction could predict a small number of mutations in the Antarctic enzyme that could result in an increase in its optimum temperature. The results of the calculation showed that this would be possible if 16 mutations were inserted from the corresponding pig enzyme into the bacterial variant. The researchers then produced this hybrid enzyme and measured its catalytic activity as a function of temperature, and it was indeed found that the new variant had a 6 °C higher optimum than the original variant and was faster than both the Antarctic and pig enzymes at 50 °C. They also solved the three-dimensional structure of the hybrid enzyme by X-ray crystallography and showed that the necessary structural changes predicted by the computer calculations had indeed taken place. Computer-based enzyme design has become a major and hotly pursued research area in recent years. The goal is to create enzymes with new properties and to do so with the help of computer calculations instead of labour-intensive experiments. "For example, this may involve creating new enzymes that catalyse chemical reactions not found in nature or changing their properties so that they can better cope with heat, cold, high pressure, increased salinity and so on. This area is therefore the subject of great biotechnological interest," notes Johan Åqvist, Professor of Theoretical Chemistry at Uppsala University.

GSK plc (LSE/NYSE: GSK) announced positive results from a Phase IIa study demonstrating that GSK3036656, a first-in-class investigational antitubercular agent, was well tolerated and showed early bactericidal activity with a low, once-daily oral dose after 14 days of treatment in participants with drug-susceptible pulmonary tuberculosis. These results demonstrate the potential for GSK3036656 to be a component of simpler treatment regimens in the future which could help address the TB epidemic. A selection of these data was presented in an oral late breaker session at the Union World Conference on Lung Health on 11 November. The TB epidemic is one of the most pressing public health challenges: over the last decade TB was the leading cause of death due to an infectious disease globally, causing approximately 1.5 million deaths annually. Earlier this year, GSK made a commitment to invest 1bn over the next decade to accelerate R&D on infectious diseases, including TB, that disproportionately impact lower-income countries. David Barros-Aguirre, Head of Global Health Medicines R&D, GSK, said: Existing treatments for TB can be complicated, of long duration and have serious side effects which significantly impact the lives of patients with TB around the world. Todays encouraging data provide a good foundation from which to investigate GSK3036656 in different combinations in Phase IIb/c studies, with the aim of contributing to shorter, simpler and better tolerated treatment regimens for patients with TB. Anti-mycobacterial activity was demonstrated both in terms of reducing the number of viable TB cells which are able to multiply (colony forming units - CFU), and an increase in the time to detect bacterial growth in culture (time to positivity - TTP). In addition, PET CT imaging of the lungs showed a reduction in TB disease over 14 days in all participants taking GSK3036656 30mg. Prof. Andreas Diacon, Chief Scientific Officer, TASK, said The data show that GSK3036656 is a potential new antibiotic for tuberculosis that can be used in low, once daily doses. This can help reduce side effects and is an important characteristic of any new TB drug. GSK3036656 is of a completely new class of antibiotics which makes the chance of drug resistance very low. I am looking forward to evaluating GSK3036656 in shorter and better tolerated combinations with other new agents to bring about a new era of tuberculosis treatment. The investigational antitubercular agent will be tested in Phase IIb/c studies in different drug regimens to determine the appropriate partner agents to complement its anti-TB action and the optimal regimen durations. The aim is to identify a GSK3036656-containing regimen with sufficient tolerability, efficacy and short enough duration to progress to Phase III with a high probability of success. These innovative studies will be conducted in collaboration with industry and academic partners and will be co-funded by the European Unions IMI2 programme. GSK works in partnership to develop new TB medicines and vaccines, focusing efforts on research and early development, and partnering with world-leading organisations and funders on late development, manufacturing and access to maximise impact for patients. About the trial Study 201214 was a single centre, Phase IIa, open-label study to investigate the early bactericidal activity (EBA), safety, and tolerability of GSK3036656 in participants with drug-sensitive pulmonary tuberculosis. The study had four cohorts, with 12 to 20 participants in each cohort. The participants were randomized in a 3:1 ratio to receive either GSK3036656 at doses 1 mg, 5 mg, 15 mg, and 30 mg or standard-of-care (SoC) regimen for drug sensitive TB (i.e. Rifafour e-275 or equivalent generic alternative), respectively. The primary endpoint was to determine the rate of change in log10colony forming units (CFU) per mL direct respiratory sputum samples over the period baseline to Day 14 (EBA CFU0-14). A key secondary outcome was the rate of change in time to sputum culture positivity (EBA TTP) over the time period baseline to Day 14 (EBA TTP0-14). GSK3036656 doses of 5 mg to 30 mg showed bactericidal activity as evidenced by both endpoints after 14 days. GSK3036656 30 mg had the highest bactericidal activity: A decline in CFU of -0.138 log10CFU/mL (95% CI: -0.167, -0.109) An increase in TTP of 0.22 log10CFU/mL (95% CI: 0.019, 0.024) GSK3036656 was generally well tolerated with no serious adverse events (SAEs) identified in the study. The percentage of participants reported with adverse events was similar between SoC and GSK3036656 and no large differences between GSK3036656 and SoC or GSK3036656 dose related trends were observed. The trial was conducted as part of the anTBiotic project, a consortium which consists of GSK Global Health Medicines R&D (Spain), the University of Troms (Norway), Forschungszentrum Borstel (Germany), the University of Cape Town (South Africa) and the TASK Foundation (South Africa). The project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 733079. About tuberculosis Tuberculosis is the leading cause of death due to an infectious disease globally, other than COVID-19, causing approximately 1.5 million deaths annually. It is caused by a bacterium called Mycobacterium tuberculosis and mainly affects the lungs, although it can affect any part of the body. Current treatment options are often inadequate for patients with TB: long and complicated courses of treatment with serious side effects mean many people struggle to adhere to the full course. As a result, the bacteria are developing resistance to existing medicines making treatment less effective. New treatments are urgently needed: the ambition is to find shorter, simpler and better tolerated treatments for TB to reduce the burden on patients and increase adherence to treatment thereby preventing further selection of resistant strains. However, developing new TB treatment regimens is challenging as they involve a combination of more than three different compounds often from multiple organisations. A collaborative approach is required to ensure researchers can access the compounds at an early stage of development to understand how they work in combination. About GSK3036656 GSK3036656 is a first-in-class investigational antitubercular agent which is being developed for the treatment of tuberculosis as part of a future combination regimen. It suppresses protein synthesis in Mycobacterium tuberculosis (Mtb) by inhibiting the enzyme leucyl t-RNA synthetase (LeuRS). GSK3036656 has demonstrated activity not only against laboratory strains of Mtb, but also against a selection of Drug Sensitive TB (DS-TB), Multi Drug Resistant TB (MDR-TB) and Extensively Drug Resistant TB (XDR-TB) clinical isolates. Animal models of TB infection have shown that GSK3036656 is potent in vivo. The compound is the result of a collaboration between GSK and Anacor Pharmaceuticals which led to the identification of GSK3036656 as a selective anti-mycobacterial agent that is inactive against other respiratory pathogens. About GSK GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together.