In recent years, therapeutic antibodies have transformed the treatment of cancer and autoimmune diseases. Now, researchers at Lund University in Sweden have developed a new, efficient method based on the genetic scissors CRISPR-Cas9, that facilitates antibody development. The discovery is published in Nature Communications.
Antibody drugs are the fastest growing class of drug, and several therapeutic antibodies are used to treat cancer. They are effective, often have few side effects and benefit from the body’s own immune system by identifying foreign substances in the body. By binding to a specific target molecule on a cell, the antibody can either activate the immune system, or cause the cell to self-destruct.
However, most antibody drugs used today have been developed against an antibody target chosen beforehand. This approach is limited by the knowledge of cancer we have today and restricts the discovery of new medicines to currently known targets.
“Many antibody drugs currently target the same molecule, which is a bit limiting. Antibodies targeting new molecules could give more patients access to effective treatment,” says Jenny Mattsson, doctoral student at the Department of Hematology and Transfusion Medicine at Lund University.
Another route — that pharmaceutical companies would like to go down — would be to search for antibodies against cancer cells without being limited to a pre-specified target molecule. In this way, new, unexpected target molecules could be identified. The problem is that this method (so-called “phenotypic antibody development”) requires that the target molecule be identified at a later stage, which has so far been technically difficult and time-consuming.
“Using the CRISPR-Cas9 gene scissors, we were able to quickly identify the target molecules for 38 of 39 test antibodies. Although we were certain that the method would be effective, we were surprised that the results would be this precise. With previous methods, it has been difficult to find the target molecule even for a single antibody,” says Jenny Mattsson.
The research project is a collaboration between Lund University, BioInvent International and the Foundation for Strategic Research. The researchers’ method has already been put into practical use in BioInvent’s ongoing research projects.
“We believe the method can help antibody developers and hopefully contribute to the development of new antibody-based drugs in the future,” concludes Professor Björn Nilsson, who led the project.

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DNA sequencing of bacteria found in pigs and humans in rural eastern North Carolina, an area with concentrated industrial-scale pig-farming, suggests that multidrug-resistant Staphylococcus aureus strains are spreading between pigs, farmworkers, their families and community residents, and represents an emerging public health threat, according to a study led by researchers at the Johns Hopkins Bloomberg School of Public Health.
S. aureus is commonly found in soil and water, as well as on the skin and in the upper respiratory tract in pigs, other animals, and people. It can cause medical problems from minor skin infections to serious surgical wound infections, pneumonia, and the often-lethal blood-infection condition known as sepsis. The findings provide evidence that multidrug-resistant S. aureus strains are capable of spreading and possibly causing illness in and around factory farm communities in the U.S. — a scenario the authors say researchers should continue to investigate.
The study was published online February 22 in Emerging Infectious Diseases, a journal published by the U.S. Centers for Disease Control and Prevention.
The researchers in recent years have been collecting samples of S. aureus from pigs, farmworkers, farmworkers’ family members, and community residents — including children — in the top pig-producing counties in North Carolina. For the study, they sequenced the DNA from some of these samples to determine the relation of the strains found in pigs and people. They found that the strains were very closely related, providing evidence for transmission between pigs and people. Most of the strains carried genes conferring resistance to multiple antibiotics.
“We found that these livestock-associated S. aureus strains had many genes that confer resistance to antimicrobial drugs commonly used in the U.S. industrialized pig production system,” says study first author Pranay Randad, PhD, a postdoctoral researcher in the Bloomberg School’s Department of Environmental Health and Engineering.
“These findings warrant future investigations into the transmission dynamics in nearby communities and disease burden associated with these strains in the United States,” says study senior author Christopher Heaney, PhD, associate professor in the same department. Epidemiologists have long suspected that S. aureus and other bacteria are transmitted from humans to pigs on factory farms, and thereafter evolve antibiotic resistance within the pigs. The animals are routinely given antibiotics to prevent outbreaks in their dense concentrations on factory farms. The drug-resistant bacterial strains may then be transmitted back to humans, becoming a potentially serious source of disease.

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In recent years, Heaney and colleagues have been gathering S. aureus isolates from pigs and farmworkers at factory-scale pig farms in North Carolina, one of the leading pig-farming states. Their research has shown that livestock-associated strains of S. aureus, many of them antibiotic-resistant strains, can be found not only in pigs but also in farmworkers, their family members, and residents living nearby.
For the new study they performed whole-genome sequencing on 49 of these S. aureus isolates to characterize these strains at the DNA level and get a more precise picture of their interrelatedness.
One finding was that all these isolates, whether taken from humans or pigs, belonged to a grouping of S. aureus strains known as clonal complex 9 (CC9).
“This CC9 is a novel and emerging subpopulation of S. aureus that not many people have been studying, apart from a few reports in Asia,” Randad says.
The researchers also determined from their analysis that the CC9 isolates from North Carolina were closely related, in many cases implying recent transmission between pigs and people. Moreover, virtually all of the isolates that appeared to be involved in transmission between pigs and humans were multidrug resistant, suggesting that diseases these isolates cause could be hard to treat.
The scope of the study didn’t include evaluating S. aureus-related disease among people in the affected communities, but one of the pig farmworkers who carried a CC9 isolate in their nose reported a recent skin infection.
“In other countries, such as in Europe, we see a high level of coordinated research on this topic from a public health perspective, with open access to collect bacterial isolates from pigs raised on factory farms, but so far in the U.S. not as much is being done,” Randad says.
Support for the study was provided by the Sherrilyn and Ken Fisher Center for Environmental Infectious Diseases Discovery Program at the Johns Hopkins University School of Medicine; the GRACE Communications Foundation; the National Institute for Occupational Safety and Health, the National Science Foundation, the National Institute of Allergy and Infectious Diseases, and the National Institute of Environmental Health Sciences, among other funding sources.

Two thirds of children use more than one screen at the same time after school, in the evenings and at weekends as part of increasingly sedentary lifestyles, according to new research at the University of Leicester.
An NIHR study of more than 800 adolescent girls between the ages of 11 and 14 identified worrying trends between screen use and lower physical activity — including higher BMI — as well as less sleep.
The use of concurrent screens (termed ‘screen stacking’) grew over the course of the week — with 59% of adolescents using two or more screens after school, 65% in the evenings, and 68% at weekends.
Some teens reporting using as many as four screens at one time.
But further analysis showed the use of any screen was still detrimental to the indicators of health and wellbeing. More than 90% owned or had access to a smart phone and using this after school had a knock on effect on their sleep.
Researchers from the Leicester Diabetes Centre at the University measured physical activity and sleep using accelerometers worn on participants’ wrists, while those involved in the study self-reported the number of screens they were using at the same time — such as scrolling on a mobile phone while also watching TV — as well as perceptions of self-esteem and physical self-worth.

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Dr Deirdre Harrington, Lecturer in Physical Activity for Health led the study during her time at Leicester and now works in the School of Psychological Sciences and Health at the University of Strathclyde. She said:
“Intuitively, we believe there must be negative effects on teenagers of using too many screens at the same time. Our data show it isn’t as simple as that.
“This research was done before the COVID-19 lockdown, where much more of our day is spent in front of a screen. More than ever the effects of this on adolescents need to be known — there are positives too, no doubt.
“These adolescents wore an accelerometer 24 hours a day for a week allowing us to capture their daily routines and even estimate their sleep. Uniquely, they also reported how many screens they used at the same time which is not well known.”
Melanie Davies, Professor of Diabetes Medicine at the University of Leicester and Co-Director of the Leicester Diabetes Centre based at Leicester General Hospital, said:
“Sadly, this study reminds us that we are in danger of creating a new generation of sedentary children. Increased sedentary time is closely linked to type 2 diabetes, which is increasing in younger age groups.
“The number of young people with type 2 diabetes has gone up by 50% in just five years.”
The study was supported by the National Institute for Public Health Research programme as well as the NIHR Leicester Biomedical Research Centre, and the NIHR Applied Research and Care (ARC) East Midlands.

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A new study led by Washington University School of Medicine in St. Louis and the National Cancer Institute (NCI) has identified an association between slow walking pace and an increased risk of death among cancer survivors.
While the study does not establish that slow walking is a cause of death, the association persisted across at least nine tumor types. Investigators now call for more research into these relationships and whether targeted interventions such as physical activity programs could help cancer survivors improve their ability to walk and increase survival after cancer diagnosis and treatment.
The study, a collaboration between Washington University, the NCI of the National Institutes of Health (NIH), the University of North Carolina and George Washington University, appears March 4 in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.
“Cancer survivors are living longer than ever — and that’s good news,” said first author Elizabeth A. Salerno, PhD, an assistant professor of surgery in the Division of Public Health Sciences at Washington University. “But it’s important to improve our understanding of how the diagnosis and treatment of a broad range of cancers may affect walking pace during survivorship — a potentially modifiable risk factor — which could lead to new treatment and rehabilitation strategies to improve the health of these patients.”
The researchers studied over 233,000 participants enrolled in the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study. Participants, who were ages 50 to 71, answered questionnaires about their overall health and walking pace, and whether they had any disability related to walking, such as walking at a very slow pace or being unable to walk. After the assessment, participants were followed for several years.
Compared with healthy controls enrolled in the study, cancer survivors were 42% more likely to report walking at the slowest pace and 24% more likely to report being disabled. Among cancer survivors, those who walked at the slowest pace had more than twofold increased risk of death from any cause, compared with those reporting the fastest walking pace.
The association between the slowest walking pace and a significantly increased risk of death from any cause held for nine cancer types, including breast, colon, melanoma, Non-Hodgkin lymphoma, oral, prostate, rectal, respiratory and urinary cancers. The association between mobility disability (not just slow pace) and death was even stronger and included all nine of the cancers mentioned above, plus endometrial, endocrine, ovarian and stomach cancers.
While slow walking pace also was linked to increased mortality that was due to any cause among individuals without a cancer diagnosis, the risk of death more than doubled for cancer survivors. Compared with individuals without a cancer diagnosis who walked at the fastest pace, cancer survivors who walked the slowest had more than tenfold increased risk of death from any cause. Cancer survivors with mobility disability had more than fivefold increased risk of death compared with individuals with no cancer diagnosis or disability.
The researchers noted that cancer survivors reported difficulties walking five years or more after cancer diagnosis and treatment, suggesting that the detrimental effects of cancer diagnosis and therapy are widespread across cancer types and long lasting, creating opportunities for intervening to help such patients improve their walking ability and pace.
“To our knowledge, this analysis is the first to explore the relationship between cancer, walking pace and subsequent mortality in 15 different cancer types,” said Salerno, who conducted this research while a postdoctoral researcher at the NCI. “Next steps include identifying the underlying reasons for these associations. It’s possible that slow walking may be due to the cancer itself, adverse effects of treatment, or changes in lifestyle. There is still much to be learned about these complex relationships, but our results highlight the importance of monitoring and even targeting walking pace after cancer.”
This work was supported by the Intramural Research Program of the National Cancer Institute (NCI) of the National Institutes of Health (NIH).

In order to stay alive, the cell must provide its various organelles with all the energy elements they need, which are formed in the Golgi apparatus, its centre of maturation and redistribution of lipids and proteins. But how do the proteins that carry these cargoes — the kinesins — find their way and direction within the cell’s “road network” to deliver them at the right place? Chemists and biochemists at the University of Geneva (UNIGE), Switzerland, have discovered a fluorescent chemical dye, making it possible for the first time to track the transport activity of a specific motor protein within a cell. A discovery to be read in the magazine Nature communication.
“It all started from a research that didn’t go as planned,” laughs Nicolas Winssinger, professor at the Department of Organic Chemistry of the Faculty of Science at UNIGE. “Initially, we wanted to develop a molecule that would make it possible to visualise the stress level of the cell, i.e. when it accumulates too much active oxygen species. During the experiment, the molecule did not work, but crystallised. Why did it crystallise? What were these crystals?”
Three hypotheses emerged as possible and the team reached out to Charlotte Aumeier, professor in the Department of Biochemistry of the Faculty of Sciences of the UNIGE to verify them. The first hypothesis suggested that crystallisation was due to the microtubules that polymerise. “Microtubules are small, rigid tubes that can grow or shrink and constitute the “road network” that allows molecules to move around the cell,” explains Charlotte Aumeier. The second hypothesis made Golgi’s apparatus responsible for this chemical reaction. The last possibility suggested that the crystals were the result of the small steps made by the kinesin proteins in the microtubules as they moved within the cell.
The biochemists’ little thumb
To verify these different options, the UNIGE team joined forces with the National Institute of Health (NIH) in Bethesda (USA), which specialises in electron microscopy. “We first recreated microtubules that we purified, which takes 14 hours,” explains Charlotte Aumeier. “For the kinesins, the motor proteins that move on microtubules and transport cargo, we isolated them from bacteria.” The scientists then put together about 20 different mixtures containing the small molecule QPD, which is systematically present in the crystals, and observed which solution worked. “We wanted to know what was needed to form the crystals. The microtubules? The kinesin? Yet another protein?” asks Nicolas Winssinger.
Following various experiments, the team discovered that the formation of these crystals was caused by one of the 45 types of kinesin present in the cell. “With each small step that this kinesin protein takes on the microtubule, it uses energy that leaves a trace identified by the QPD molecule,” continues the Geneva-based researcher. It is from this recognition that the crystals are formed. In this way, the crystals are chemically left behind by the passage of the kinesin, which can be tracked by scientists like a small thumb.
The opening of a new field of study
“Until now, it has not been possible to track a particular protein. With current techniques, we couldn’t separate the individual kinesins, so we couldn’t see which path they took precisely,” continues Charlotte Aumeier. “Thanks to the development of our new chemical fluorescent dye, we can observe in detail how a protein behaves, which route it takes, its direction or even its preferred path.” For the first time, scientists can visualise the walking path of motor proteins and study the fundamental question of the transport activity and distribution of cargoes in cells.

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Researchers at Scripps Institution of Oceanography at UC San Diego examining 14 years of hospital admissions data conclude that the fine particles in wildfire smoke can be several times more harmful to human respiratory health than particulate matter from other sources such as car exhaust. While this distinction has been previously identified in laboratory experiments, the new study confirms it at the population level.
This new research work, focused on Southern California, reveals the risks of tiny airborne particles with diameters of up to 2.5 microns, about one-twentieth that of a human hair. These particles — termed PM2.5 — are the main component of wildfire smoke and can penetrate the human respiratory tract, enter the bloodstream and impair vital organs.
The study appears March 5 in the journal Nature Communications by researchers from Scripps Institution of Oceanography and the Herbert Wertheim School of Public Health and Human Longevity Science at UC San Diego. It was funded by the University of California Office of the President, the National Oceanic and Atmospheric Administration (NOAA), the Alzheimer’s Disease Resource Center for Advancing Minority Aging Research at UC San Diego and theOffice of Environmental Health Hazard Assessment.
To isolate wildfire-produced PM2.5 from other sources of particulate pollution, the researchers defined exposure to wildfire PM2.5 as exposure to strong Santa Ana winds with fire upwind. A second measure of exposure involved smoke plume data from NOAA’s Hazard Mapping System.
A 10 microgram-per-cubic meter increase in PM2.5 attributed to sources other than wildfire smoke was estimated to increase respiratory hospital admissions by 1 percent. The same increase, when attributed to wildfire smoke, caused between a 1.3 to 10 percent increase in respiratory admissions.
Corresponding author Rosana Aguilera said the research suggests that assuming all particles of a certain size are equally toxic may be inaccurate and that the effects of wildfires — even at a distance — represent a pressing human health concern.
“There is a daily threshold for the amount of PM2.5 in the air that is considered acceptable by the county and the Environmental Protection Agency (EPA),” said Aguilera, a postdoctoral scholar at Scripps Institution of Oceanography. “The problem with this standard is that it doesn’t account for different sources of emission of PM2.5.”
As of now, there is not a consensus as to why wildfire PM2.5 is more harmful to humans than other sources of particulate pollution. If PM2.5 from wildfires is more dangerous to human lungs than that of ambient air pollution, the threshold for what are considered safe levels of PM2.5 should reflect the source of the particles, especially during the expanding wildfire season. This is especially relevant in California and other regions where most PM2.5 is expected to come from wildfires.
In Southern California, the Santa Ana winds drive the most severe wildfires and tend to blow wildfire smoke towards populated coastal regions. Climate change delays the start of the region’s rainy season, which pushes wildfire season closer to the peak of the Santa Ana winds in early winter. Additionally, as populations grow in wildland urban interface areas, the risks of ignitions and impacts of wildfire and smoke increase for those who live inland and downwind.
Coauthor Tom Corringham points to the implications for climate change: “As conditions in Southern California become hotter and drier, we expect to see increased wildfire activity. This study demonstrates that the harm due to wildfire smoke may be greater than previously thought, bolstering the argument for early wildfire detection systems and efforts to mitigate climate change.”

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RCSI researchers have discovered a new way to ‘put the brakes’ on excessive inflammation by regulating a type of white blood cell that is critical for our immune system.
The discovery has the potential to protect the body from unchecked damage caused by inflammatory diseases.
The paper, led by researchers at RCSI University of Medicine and Health Sciences, is published in Nature Communications.
When immune cells (white blood cells) in our body called macrophages are exposed to potent infectious agents, powerful inflammatory proteins known as cytokines are produced to fight the invading infection. However, if these cytokine levels get out of control, significant tissue damage can occur.
The researchers have found that a protein called Arginase-2 works through the energy source of macrophage cells, known as mitochondria, to limit inflammation. Specifically they have shown for the first time that Arginase-2 is critical for decreasing a potent inflammatory cytokine called IL-1.
This discovery could allow researchers to develop new treatments that target the Arginase-2 protein and protect the body from unchecked damage caused by inflammatory diseases.
“Excessive inflammation is a prominent feature of many diseases such as multiple sclerosis, arthritis and inflammatory bowel diseases. Through our discovery, we may be able to develop novel therapeutics for the treatment of inflammatory disease and ultimately improve the quality of life for people with these conditions,” commented senior author on the paper Dr Claire McCoy, Senior Lecturer in Immunology at RCSI.
The study was led by researchers at the School of Pharmacy and Biomolecular Sciences, RCSI (Dr Claire McCoy, Dr Jennifer Dowling and Ms Remsha Afzal) in collaboration with a network of international researchers from Australia, Germany, and Switzerland.
The research was funded by Science Foundation Ireland, with initial stages of the research originating from a grant from the National Health Medical Research Council, Australia.

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