Tests can reveal whether an antibody can turn into a killer

What makes a soldier switch sides? That is a really good question. Especially when the soldier is an antibody that is supposed to defend the body against one of the world’s most dangerous snake venoms but instead ends up helping the venom kill the body.
The question has become topical after a group of DTU researchers slightly changed how they tested an antibody that had previously proven promising as an antidote to snake venom. In the first experiment on mice, the damaging effect on muscle tissue from the venom of Bothrops Asper, a Costa Rican lancehead snake, was neutralized as expected. But in the second experiment, the antibody enhanced the snake venom’s potency, so that it no longer just affected the muscle tissue, but ended up killing the mice.
When and how the antibody was administered made the difference between life and death. In the first experiment, snake venom and antibody were mixed together for 30 minutes before being injected into the muscle tissue of the mouse. This method is only slightly similar to treating a real snakebite. In the second experiment, the researchers simulated the usual real-world scenario, where antivenom is administered after a snakebite: First, they injected the poison into the muscle tissue of the mouse. Three minutes later, they injected the antibody into the mouse’s veins.
“The fact that the antibody amplifies the toxin when venom and antidote are administered in different ways is an incredibly interesting discovery from a research point of view,” says Postdoc Christoffer Vinther Sørensen from DTU, who was the one testing the antibody when the observation was made.
“This is a significant discovery we have arrived at,” says Professor Bruno Lomonte from the University of Costa Rica. Alongside his colleague, Professor Julián Fernández, he has collaborated with Christoffer Vinther Sørensen and his project supervisor at DTU, Professor Andreas Hougaard Laustsen-Kiel, for the past 4 years. They hope that the discovery will contribute to expediting the development of the next generation of antivenom, ensuring that many people in need can benefit from it sooner.
The discovery has just been published in Nature Communications in the paper “Antibody-dependent enhancement of toxicity of myotoxin II from Bothrops asper.”
The first time ADET is observed in connection with animal venoms
The phenomenon, which the researchers have observed, is known as antibody-dependent enhancement of toxicity (ADET) and has not previously been observed in connection with toxins from the animal world and it remains a mystery in most areas. For example, scientists do not know how an antibody designed to combat venom can switch sides and instead intensify the toxins’ attacks on the body.

“We haven’t figured out how this happens, but it helps to identify another important aspect that should be tested when working with antibodies,” says Christoffer Vinther Sørensen.
His research project is part of international research work aimed at finding a broad-spectrum antivenom based on human antibodies that can be used as treatment against the world’s most dangerous snake venoms.
“Antibodies can fail in many ways. By mapping these ways, we and other antidote researchers in the future can ensure that promising antibodies are tested as soon as possible in the most essential experiments. We hope that this allows us to discard antibodies that are not optimal and quickly arrive at a final antivenom that can neutralize the world’s most dangerous snake venoms,” says Christoffer Vinther Sørensen and adds:
“While we don’t know why a ‘soldier’ switches sides, we now know that it’s something to keep an eye on, even with our close friends, the antibodies.”
FACTS
ADET — A complicated phenomenon
ADET, antibody-dependent enhancement of toxicity, is an immunological phenomenon similar to the phenomenon of antibody-dependent enhancement, ADE, which is already the subject of intense research.

ADE is best known from viral infections, where it can occur when antibodies from a previous infection with a particular virus bind to a new strain of the same virus or to a related virus, but do not neutralize it. This non-neutralising binding may then, in some cases, enhance the harmful effect of the virus, for example by making it easier for the virus to penetrate the body’s cells.
Antibodies play a crucial role in the body’s defense against pathogens. They are produced in the immune system and bind to bacteria, viruses, or toxins, preventing them from developing, penetrating the nerve pathways, or exerting their toxic effects.
NEW GENERATION OF ANTIDOTES
More than 100,000 people die annually from snakebites
In 2017, the World Health Organization (WHO) added snakebites to the list of neglected tropical diseases. Every year, 5.4 million people are bitten by snakes. Most happen in poor areas of the world where there is no viable market for pharmaceutical companies. Approximately 100,000 die from snakebites yearly, while three times as many are permanently disabled.
An international group of researchers, led by Professor Andreas Hougaard Laustsen-Kiel from DTU, is working to develop a new generation of broad-spectrum antivenoms that are effective against many snake species. The group aims to base antidotes on antibodies compatible with the human immune system and can eventually be cultivated in cell tanks.

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Energy-starved breast cancer cells consume their surroundings for fuel

Breast cancer cells ingest and consume the matrix surrounding them to overcome starvation, according to a new study publishing January 16 in the open access journal PLOS Biology, by Elena Rainero of the University of Sheffield, UK, and colleagues. The finding elucidates a previously unknown mechanism of cancer cell survival, and may offer a new target for therapy development.
Cells in the breast, including tumor cells, are embedded in a meshwork called the extracellular matrix (ECM). Nutrients are scarce in the ECM, due to limited blood flow, and become even scarcer as tumor cells grow. And yet they continue to grow, leading the authors to investigate how tumor cells supply themselves with the raw materials to support that growth.
To do so, they seeded breast adenocarcinoma cells into either collagen (a major component of the ECM) or a commercial matrix preparation, or onto plastic, with or without certain critical amino acids. Without those amino acids, cells on plastic fared poorly compared to those in one or the other matrix. Similar results were seen with other matrix models — the tumor cells were able to overcome the reduction of amino acids when surrounded by matrix.
Next, by fluorescently labeling the collagen and watching its journey through the cell, the authors showed that the cells took up ECM and broke it down in digestive compartments called lysosomes; when the ECM was chemically treated to cross-link its components, the cells were unable to ingest it. Further investigation indicated that uptake was through an ingestion process called macropinocytosis, in which the cell engulfs large quantities of extracellular material.
What were the tumor cells after? Analysis of their metabolome indicated that procurement and breakdown of two amino acids, tyrosine and phenylalanine, dominated the metabolic changes in response to starvation. The authors noted that these two can serve as the raw material for energy production through the mitochondrial tricarboxylic acid (Krebs) cycle. When they knocked down HPDL, a central enzyme in the pathway from phenylalanine to the TCA, cell growth was significantly impaired. Blocking or reducing expression of HPDL, or the macropinocytosis promoter PAK1, reduced the ability of tumor cells to migrate and to invade surrounding tissue.
“Our results indicate that breast cancer cells take advantage of nutrients in the extracellular matrix in times of nutrient starvation, and that this process depends on both macropinocytosis and metabolic conversion of key amino acids to energy-releasing substrates,” Rainero said. “HPDL-mediated metabolism of tyrosine and phenylalanine could represent a metabolic vulnerability of cancer cells thriving in a nutrient deprived microenvironment.”
The authors add, “This study identified a novel mechanism employed by breast cancer cells to survive in the challenging environment they are in within tumours. As sources of food are scarce, cancer cells gain the ability to eat and digest components of the matrix around them. Here we have identified a key metabolic process that the cells need to be able to take advantage of the matrix, which could represent a novel therapeutic target.”

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Amnesia caused by head injury reversed in early mouse study

A mouse study designed to shed light on memory loss in people who experience repeated head impacts, such as athletes, suggests the condition could potentially be reversed. The research in mice finds that amnesia and poor memory following head injury is due to inadequate reactivation of neurons involved in forming memories.
The study, conducted by researchers at Georgetown University Medical Center in collaboration with Trinity College Dublin, Ireland, is reported January 16, 2024, in the Journal of Neuroscience.
Importantly for diagnostic and treatment purposes, the researchers found that the memory loss attributed to head injury was not a permanent pathological event driven by a neurodegenerative disease. Indeed, the researchers could reverse the amnesia to allow the mice to recall the lost memory, potentially allowing cognitive impairment caused by head impact to be clinically reversed.
The Georgetown investigators had previously found that the brain adapts to repeated head impacts by changing the way the synapses in the brain operate. This can cause trouble in forming new memories and remembering existing memories. In their new study, investigators were able to trigger mice to remember memories that had been forgotten due to head impacts.
“Our research gives us hope that we can design treatments to return the head-impact brain to its normal condition and recover cognitive function in humans that have poor memory caused by repeated head impacts,” says the study’s senior investigator, Mark Burns, PhD, a professor and Vice-Chair in Georgetown’s Department of Neuroscience and director of the Laboratory for Brain Injury and Dementia.
In the new study, the scientists gave two groups of mice a new memory by training them in a test they had never seen before. One group was exposed to a high frequency of mild head impacts for one week (similar to contact sport exposure in people) and one group were controls that didn’t receive the impacts. The impacted mice were unable to recall the new memory a week later.
“Most research in this area has been in human brains with chronic traumatic encephalopathy (CTE), which is a degenerative brain disease found in people with a history of repetitive head impact,” said Burns. “By contrast, our goal was to understand how the brain changes in response to the low-level head impacts that many young football players regularly experience.”
Researchers have found that, on average, college football players receive 21 head impacts per week with defensive ends receiving 41 head impacts per week. The number of head impacts to mice in this study were designed to mimic a week of exposure for a college football player, and each single head impact by itself was extraordinarily mild.

Using genetically modified mice allowed the researchers to see the neurons involved in learning new memories, and they found that these memory neurons (the “memory engram”) were equally present in both the control mice and the experimental mice.
To understand the physiology underlying these memory changes, the study’s first author, Daniel P. Chapman, Ph.D., said, “We are good at associating memories with places, and that’s because being in a place, or seeing a photo of a place, causes a reactivation of our memory engrams. This is why we examined the engram neurons to look for the specific signature of an activated neuron. When the mice see the room where they first learned the memory, the control mice are able to activate their memory engram, but the head impact mice were not. This is what was causing the amnesia.”
The researchers were able to reverse the amnesia to allow the mice to remember the lost memory using lasers to activate the engram cells. “We used an invasive technique to reverse memory loss in our mice, and unfortunately this is not translatable to humans,” Burns adds. “We are currently studying a number of non-invasive techniques to try to communicate to the brain that it is no longer in danger, and to open a window of plasticity that can reset the brain to its former state.”
In addition to Burns and Chapman the authors include Stefano Vicini at Georgetown University and Sarah D. Power and Tomás J. Ryan at Trinity College Dublin, Ireland.
This work was supported by the Mouse Behavior Core in the Georgetown University Neuroscience Department and by the National Institutes of Health (NIH) / National Institute of Neurological Disorders and Stroke (NINDS) grants R01NS107370 & R01NS121316. NINDS also supported F30 NS122281 and the Neural Injury and Plasticity Training Grant housed in the Center for Neural Injury and Recovery at Georgetown University (T32NS041218). Seed funding is from the CTE Research Fund at Georgetown.
The authors report having no personal financial interests related to the study.

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'Smart glove' can boost hand mobility of stroke patients

This month, a group of stroke survivors in B.C. will test a new technology designed to aid their recovery, and ultimately restore use of their limbs and hands.
Participants will wear a new groundbreaking “smart glove” capable of tracking their hand and finger movements during rehabilitation exercises supervised by Dr. Janice Eng, a leading stroke rehabilitation specialist and professor of medicine at UBC.
The glove incorporates a sophisticated network of highly sensitive sensor yarns and pressure sensors that are woven into a comfortable stretchy fabric, enabling it to track, capture and wirelessly transmit even the smallest hand and finger movements.
“With this glove, we can monitor patients’ hand and finger movements without the need for cameras. We can then analyze and fine-tune their exercise programs for the best possible results, even remotely,” says Dr. Eng.
Precision in a wearable device
UBC electrical and computer engineering professor Dr. Peyman Servati, PhD student Arvin Tashakori and their team at their startup, Texavie, created the smart glove for collaboration on the stroke project. Dr. Servati highlighted a number of breakthroughs, described in a paper published last week in Nature Machine Intelligence.
“This is the most accurate glove we know of that can track hand and finger movement and grasping force without requiring motion-capture cameras. Thanks to machine learning models we developed, the glove can accurately determine the angles of all finger joints and the wrist as they move. The technology is highly precise and fast, capable of detecting small stretches and pressures and predicting movement with at least 99-per-cent accuracy — matching the performance of costly motion-capture cameras.”
Unlike other products in the market, the glove is wireless and comfortable, and can be easily washed after removing the battery. Dr. Servati and his team have developed advanced methods to manufacture the smart gloves and related apparel at a relatively low cost locally.

Augmented reality and robotics
Dr. Servati envisions a seamless transition of the glove into the consumer market with ongoing improvements, in collaboration with different industrial partners. The team also sees potential applications in virtual reality and augmented reality, animation and robotics.
“Imagine being able to accurately capture hand movements and interactions with objects and have it automatically display on a screen. There are endless applications. You can type text without needing a physical keyboard, control a robot, or translate American Sign Language into written speech in real time, providing easier communication for individuals who are deaf or hard of hearing.”

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Unraveling the role of supersulfides in regulating mitochondrial function and longevity

Supersulfides are gaining prominence for their occurrence as low-molecular-weight thiols or persulfidated cysteine residues, observed more frequently in both prokaryotic and eukaryotic cells. These compounds, which are characterized by sulfur-sulfur bonds, play key roles in energy metabolism, embryonic development, cardiac function, tumorigenesis, innate immunity, antiviral defense, and the prevention of chronic pulmonary disorders. Cysteinyl-tRNA synthetase (CARS) is pivotal across diverse organisms for synthesizing and integrating these supersulfides into proteins. However, the in vivo physiological functions of supersulfides produced by CARS remain unclear.
Now, a study conducted by a research team from Japan has revealed that cysteine persulfide (CysSSH) — a supersulfide synthesized by CARS — regulates cellular longevity in budding yeast. This study, published in Redox Biology, was led by Akira Nishimura from Nara Institute of Science and Technology (NAIST).
To investigate the impact of CARS and supersulfides in yeast, the researchers genetically engineered a mutant strain of Saccharomyces cerevisiae. This strain carried a mutated CARS gene capable of protein synthesis but exhibited decreased production of CysSSH.
Initially, the team demonstrated that the mutant yeast exhibited a markedly reduced lifespan compared to normal (or ‘wild-type’, WT) yeast. About 50% of mutant cells became nonviable within the first week whereas WT cells remained viable for twice the period. Interestingly, the researchers restored the normal longevity in the mutant strain by externally inducing the production of regular CARS in both the cells’ cytosol and mitochondria.
Subsequently, the researchers conducted additional experiments to gain a comprehensive understanding of the effects of the introduced mutation and consequently, the significance of CysSSH and associated supersulfides. Their examination revealed that the CARS-deficient yeast mutant suffered from abnormal mitochondrial energy metabolism, as well as an increased stress response throughout the endoplasmic reticulum. However, supplying the mutant cells with supersulfide donors, like Sodium disulfide (Na2S2) could reverse these detrimental effects. “To the best of our knowledge, this is the first demonstration of CARS- and supersulfide-dependent longevity control, mediated by mitochondrial respiration and the regulation of protein quality,” highlights Nishimura.
Notably, this study has important implications not only for yeast, but for countless lifeforms. “Since supersulfide-related lifespan regulation mechanisms are likely to be widely conserved in higher organisms including humans, the intake of supersulfides from supplements and other sources may contribute to the prevention of aging and the extension of a healthy life span,” remarks Nishimura. Moreover, abnormal mitochondrial metabolism and endoplasmic reticulum stress are hallmarks of various disorders, such as cardiac diseases, Alzheimer’s, Parkinson’s, and cancer. Thus, supersulfides may hold tremendous untapped potential in the medical field.
Inspired by the results of their study and with eyes on the future, Nishimura concludes, “Given the promising implications of the present experimental findings and the remarkable potency of supersulfides, continued investigation of supersulfides will surely aid the discovery and development of new drugs for challenging diseases.”

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Squishy, metal-free magnets to power robots and guide medical implants

“Soft robots,” medical devices and implants, and next-generation drug delivery methods could soon be guided with magnetism — thanks to a metal-free magnetic gel developed by researchers at the University of Michigan and the Max Planck Institute for Intelligent Systems in Stuttgart, Germany.
The material is the first in which carbon-based, magnetic molecules are chemically bonded to the molecular network of a gel, creating a flexible, long-lived magnet for soft robotics. The study describing the material was published today in the journal Matter.
Creating robots from flexible materials allows them to contort in unique ways, handle delicate objects and explore places that other robots cannot. More rigid robots would be crushed by the deep ocean’s pressure or could damage sensitive tissues in the human body, for example.
“If you make robots soft, you need to come up with new ways to give them power and make them move so that they can do work,” said Abdon Pena-Francesch, assistant professor of materials science and engineering affiliated with the Robotics Institute at the University of Michigan and a corresponding author of the study.
Today’s prototypes typically move with hydraulics or mechanical wires, which require the robot to be tethered to a power source or controller, also limiting where they can go. Magnets could unleash these robots, enabling them to be moved by magnetic fields.
Conventional, metallic magnets introduce their own complications, however. They could reduce the flexibility of soft robots and be too toxic for some medical applications.
The new gel could be a nontoxic alternative for medical operations, and further modifications to the magnet’s chemical structure could help it degrade in the environment and human body. Such biodegradable magnets could be used in capsules that are guided to targeted locations of the body to release medicine.

“If these materials can safely degrade in your body, you don’t have to retrieve them with another surgery later,” Pena-Francesch said. “This is still pretty exploratory, but these materials could enable newer, cheaper medical operations some day.”
The team’s gel consists solely of carbon-based molecules. The key ingredient is TEMPO, a molecule with a “free” electron that is not paired up with another electron inside an atomic bond. The spin of every unpaired TEMPO electron in the gel aligns under a magnetic field, which attracts the gel to other magnetic materials.
Additional “cross-linking molecules” in the gel act like a frame that connects the TEMPO molecules to a solid network structure while forming a protective cage around the TEMPO electrons. That cage prevents the unpaired electrons from forming bonds, which would remove the gel’s magnetic properties.
“Earlier studies soaked these small, magnetic molecules into a gel, but they could leak out of the gel,” said Zane Zhang, a doctoral student in materials science and engineering and co-author of the study. “By integrating the magnetic molecules into the cross-linked gel network, they are fixed inside.”
Locking the TEMPO molecules inside the material ensures that the gel does not leak potentially harmful TEMPO molecules into the body and allows the material to retain its magnetic properties for more than a year.
While weaker than metallic magnets, the TEMPO magnets are strong enough to be pulled and bent with another magnet. Their weaker magnetism also has some upsides — TEMPO magnets can be photographed by an MRI, unlike stronger magnets that can distort MRI images to the point of uselessness.
“Medical devices using our magnets could be used to deliver drugs to target locations and measure tissue adhesion and mechanics in the GI tract under MRI imaging,” said Metin Sitti, former director of the Physical Intelligence Department at Max Planck Institute for Intelligent Systems and a corresponding author of the study.
The research is funded by the American Chemical Society Petroleum Research Fund, Max Planck Society and the European Research Council Advanced Grant Soft-bodied Miniature Mobile Robots program. The material was built in the BioInspired Materials Laboratory and characterized in the Michigan Center for Materials Characterization.
Pena-Francesch is also an assistant professor of chemical engineering and macromolecular science and engineering.

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'Feel good' hormone could explain why exercise helps boost your brain

A study exploring the mechanisms behind why cognitive performance improves in response to exercise, has found that dopamine plays a key role.
The neurotransmitter and hormone — which is tied to pleasure, satisfaction and motivation — is known to increase when you work out. New findings suggest it is also linked to faster reaction time during exercise.
The researchers behind the discovery say it could lead to a new therapeutic pathway for cognitive health, because of dopamine’s significant role in several conditions including Parkinson’s disease, schizophrenia, ADHD, addiction, and depression.
They measured the release of dopamine in the brain using a sophisticated scanning device, known as a positron emission tomography (PET). It tracks the metabolic and biochemical activity of the cells in the body.
The results revealed that when a participant cycled lying down in the machine, their brain increased the amount of dopamine release, and that this process was linked with improved reaction time.
Dr Joe Costello, from the University’s School of Sport, Health & Exercise Science (SHES), said: “We know cardiovascular exercise improves cognitive performance, but the exact mechanisms behind this process have not been rigorously investigated in humans until now.
“Using novel brain imaging techniques, we were able to examine the role dopamine plays in boosting brain function during exercise, and the results are really promising. Our current study suggests the hormone is an important neuromodulator for improved reaction time.

“These findings support growing evidence that exercise prescription is a viable therapy for a host of health conditions across the lifespan.”
As part of the study, three experiments were carried out with 52 male participants overall. In the first, individuals were asked to carry out cognitive tasks at rest and while cycling in the PET scanner, so the team could monitor the movement of dopamine in their brain.
The second used electrical muscle stimulation to test whether forced muscle movement to stimulate exercise would also improve cognitive performance. The final experiment combined both voluntary and involuntary exercise.
In the experiments where voluntary exercise was carried out, cognitive performance improved. This was not the case when only forced electrical stimulation was used.
Soichi Ando, Associate Professor in the Health & Sports Science Laboratory at the University of Electro-Communications in Japan, said: “We wanted to remove voluntary muscle movement for part of the study, to see if the process in which acute exercise improves cognitive performance is present during manufactured exercise. But our results indicate that the exercise has to be from the central signals of the brain, and not just the muscle itself.
“This suggests that when we tell our central command to move our body during a workout, that’s the process which helps the dopamine release in the brain.”
The team’s previous study examined the relationship between oxygen levels, cognitive performance and exercise, to test the theory that the more oxygen we breathe during a workout, the more awake our brain is. They found no change to an individual’s reaction time when cycling both inside and outside of an environment with low levels of oxygen (hypoxia).

“These latest findings support our previous theory that cognitive performance during exercise is affected by changes to brain regulating hormones, including dopamine,” added Dr Costello.
“There could also be a number of other psychophysiological factors including cerebral blood flow, arousal and motivation that play a part.”
The paper, published in The Journal of Physiology, says further studies are urgently needed to fully understand how dopamine release is linked to cognitive performance following exercise.
The authors also recognise limitations to the sample size being relatively small, and recommend more participants are needed in future experiments, from a range of populations including women and older individuals, over a longer period of time.
The study was a collaboration between the University of Portsmouth and University of Chichester in England; the University of Electro-Communications, Tohoku University, Meiji Yasuda Life Foundation of Health and Welfare, and Setsunan University in Japan; University Sultan Zainal Abidin in Malaysia; and Da-Yeh University in Taiwan.

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One-step synthesis of the most common, yet highly intricate, antibiotic molecular scaffold

While we appear to live in a world of plenty, behind the scenes, sourcing sufficient amounts of key ingredients can be challenging. For example, the synthesis of certain antibiotics, beta-lactam antibiotics, requires certain molecules in large quantities, and getting enough of these molecules has historically been difficult.
Now, in a study recently published in Nature Catalysis, researchers from Osaka University have unveiled a new, simplified way to synthesize the intricate beta-lactam scaffold that is characteristic of beta-lactam antibiotics.
Penicillin, the first mass-produced antibiotic, is an example of a beta-lactam antibiotic. These antibiotics are the first choice for certain bacterial infections because they are more selective and less toxic than most drugs. Unsurprisingly, there are dozens of beta-lactam antibiotics approved for clinical use and under development.
Unfortunately, synthesizing these antibiotics in the laboratory has been challenging owing to their small but intricate structure. Thus, catalysts are typically needed to facilitate critical steps during synthesis. One catalyst, known as a Fischer-carbene complex, works well but needs to be used in large quantities. The synthesis of a Fischer-carbene catalyst that works in small quantities was the goal of the research team’s study.
“Our new catalytic system can generate Fischer-carbene complexes from organosilicon compounds, which are non-toxic,” explains Tetsuya Inagaki, lead author of the study. “What’s more, we were able to isolate and characterize a key intermediate: a siloxycarbene-palladium complex.”
Unlike previous Fischer-carbene synthetic protocols, the process does not result in toxic chromium waste and does not require photo-irradiation. The reaction proceeds in just one step, is operationally straightforward, and requires only a small quantity of catalyst. The researchers used it to prepare the scaffold of the thienamycin antibiotic in 94% yield.
“We’re excited because our research will help synthesize Fischer-carbene catalysts that are otherwise difficult to isolate, and provide access to structurally complicated beta-lactam building blocks in one reaction vessel,” says Mamoru Tobisu, senior author. “We look forward to applying our reaction protocol to other classes of synthetic targets.”
This work is an important step forward in simplifying the synthesis of beta-lactams, the most common molecular scaffold of antibiotics. Because the synthetic protocol is simple and minimally toxic, applications to further chemical transformations should be straightforward.

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Warning of further measles outbreaks as cases rise

Image source, PA MediaOprah FlashBBC News West MidlandsPA MediaWest MidlandsPublished2 hours agoHealth officials have warned of further measles outbreaks across England after cases in the West Midlands rose by more than 30% in less than a week.The region has seen the largest surge in cases outside London, with more than 300 suspected infections reported between 23 October last year and Monday.Dr Ronny Cheung, children’s consultant, warned the infection “at best will cause children great discomfort and at worst deaths”.Official figures show uptake of the measles, mumps and rubella (MMR) vaccine across the country is at its lowest point in more than a decade.In 2022/23, some 84.5% of youngsters in the country had received both doses of the jab by the time they were five years old – the lowest level since 2010/11. Up to 92.5% had received one dose, figures show.UK Health Security Agency (UKHSA) data released on Monday has shown there were 198 lab-confirmed cases in the West Midlands and 104 “likely” cases.The majority (80%) have been found in Birmingham while 8% were identified in Coventry, with the rest spread across surrounding areas.This has risen from 133 confirmed and 96 suspected cases, reported on 11 October last year.Image source, ReutersUnvaccinated children who come into contact with the disease are being advised to stay at home for 21 days.Dr Cheung, officer for health services at the Royal College of Paediatrics and Child Health (RCPCH) said: “[We need to] reassure people about the benefits and remind people of the potential risks of measles, which I think a lot of people have forgotten about.”Asked if the country would see more outbreaks outside of the West Midlands, he said: “I’m afraid to say that we almost certainly will, partly because we know that vaccination rates are very low and they are not equally distributed.”There are areas where vaccination rates are much lower than others, usually in urban conurbations.’One in 5,000 die'”Also measles is incredibly contagious, so if you have pockets where lots of people are not immunised, you only need a few cases to cause a pretty significant outbreak. So, unfortunately this is something that is going to occur.”Helen Bedford, professor of children’s health at UCL Great Ormond Street Institute of Child Health, urged people to get vaccinated.”About one in 1,000 people with measles develop inflammation of the brain and even in high-income countries like the UK, about one in 5,000 die from the infection,” she said.”Measles is often more severe in adults. Apart from managing the symptoms of measles, there is no treatment.”There is no upper age limit for vaccination, so if you or your loved ones have missed out, now is the time to get that protection. We can stop this infection in its tracks with vaccination.” Follow BBC West Midlands on Facebook,

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Cloned rhesus monkey created to speed medical research

Published1 hour agoShareclose panelShare pageCopy linkAbout sharingImage source, Zhaodi Liao, NatureBy Pallab GhoshScience correspondentChinese researchers have cloned the first rhesus monkey, a species which is widely used in medical research because its physiology is similar to humans.They say they could speed up drug testing, as genetically identical animals give like-for-like results, providing greater certainty in trials.Previous attempts to clone a rhesus have either not led to births or the offspring have died a few hours later. One animal welfare group has said it is “deeply concerned” by the development.In mammals, sexual reproduction leads to offspring made up of a mixture of genes from their father and mother. In cloning, techniques are used to create a genetically identical copy of a single animal. The most famous cloned animal, Dolly the sheep, was created in 1996. Scientists reprogrammed a cell from another sheep to turn them into embryos which are building block cells that can grow into any part of an organism. These embryos were then implanted into Dolly’s surrogate mother. Writing in the journal Nature communications, the researchers say they have essentially done the same thing but with a rhesus monkey. They say that the animal has remained healthy for more than two years, indicating the cloning process was successful. Dr Falong Lu of the University of Chinese Academy of Sciences told BBC News that ”everyone was beaming with happiness” at the successful outcome.But a spokesperson for the UK’s Royal Society for the Prevention of Cruelty to Animals (RSPCA) said that the organisation believed that the animal suffering caused outweighed any immediate benefit to human patients. Rhesus monkeys are found in the wild in Asia, with populations in Afghanistan through India, Thailand, Vietnam and China. They are used in experiments to study infection and immunity.The first macaque monkeys were cloned in 2018, but rhesus monkeys are preferred for medical researchers, because of their genetic similarity to humans.Image source, Chinese Academy of SciencesThe problem with this method of cloning adult cells to become embryonic is that in most attempts, mistakes are made in the reprogramming, and very few end up becoming born and fewer still are born healthy – between 1 and 3% in most mammals. And it has proved harder still with rhesus monkeys, with no births until the research team succeeded two years ago.They discovered that in failed rhesus attempts, the placentas, which provide oxygen and nutrients to the growing foetus, were not reprogrammed properly by the cloning process and so did not develop normally. The researchers got around the problem by not using the part of the cloned embryo that goes on to develop into the placenta – the outer part. As the graphic below shows, they removed the inner cells – which develop into the body of the animal and inserted them into a non-cloned outer embryo – which they hoped would develop into a normal placenta.The researchers used 113 embryos, 11 of which were implanted and achieved two pregnancies and one live birth.They named the monkey “ReTro”, after the scientific method, called “trophoblast replacemement”, used to produce the animal.The RSPCA said it had grave misgivings about the research.”There is no immediate application for this study. We are expected to assume that human patients will benefit from these experiments, but any real-life applications would be years away and it is likely that more animal ‘models’ will be necessary in developing these technologies,” a spokesperson said.”The RSPCA is deeply concerned about the very high numbers of animals who experience suffering and distress in these experiments and the very low success rate. Primates are intelligent and sentient animals, not just research tools”.Prof Robin Lovell-Badge, of the Francis Crick institute in London, who strongly supports animal research when the benefits to patients outweigh the suffering to animals, has similar concerns.”Having animals of the same genetic make-up will reduce a source of variation in experiments. But you have to ask if it is really worth it.”The number of attempts they had is enormous. They have had to use many embryos and implant them into many surrogate mothers to get one live born animal.”Prof Lovell-Badge also has concerns that the scientists have produced only one live birth.”You cannot make any conclusions about the success rate of this technique when you have one birth. It’s nonsense to ever propose you can. You need at least two, but preferably more.”In response, Dr Falong Lu told BBC News that the team’s aim is to obtain more cloned monkeys while reducing the number of embryos used. He added that all ethical approvals had been obtained for the research.”All animal procedures in our research adhered to the guidelines set by the Animal Use and Care Committees at the Shanghai Institute of Biological Science, Chinese Academy of Sciences (CAS), and the Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology. The protocol has been approved by the Animal Use and Care Committee of the CAS Center for Excellence in Brain Science and Intelligence Technology”.Follow Pallab on X, formerly known as TwitterMore on this storyFirst monkey clones created in the labPublished24 January 2018Twenty years on from Dolly the sheepPublished4 July 2016Related Internet LinksChinese Academy of SciencesThe BBC is not responsible for the content of external sites.

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