The new approach uses samples from infected humans to allow real-time monitoring of pathogens circulating in human populations, and enable vaccine-evading bugs to be quickly and automatically identified. This could inform the development of vaccines that are more effective in preventing disease.

The approach can also quickly detect emerging variants with resistance to antibiotics. This could inform the choice of treatment for people who become infected — and try to limit the spread of the disease.

It uses genetic sequencing data to provide information on the genetic changes underlying the emergence of new variants. This is important to help understand why different variants spread differently in human populations.

There are very few systems in place to keep watch for emerging variants of infectious diseases, apart from the established COVID and influenza surveillance programmes. The technique is a major advance on the existing approach to these diseases, which has relied on groups of experts to decide when a circulating bacteria or virus has changed enough to be designated a new variant.

By creating ‘family trees’, the new approach identifies new variants automatically based on how much a pathogen has changed genetically, and how easily it spreads in the human population — removing the need to convene experts to do this.

It can be used for a broad range of viruses and bacteria and only a small number of samples, taken from infected people, are needed to reveal the variants circulating in a population. This makes it particularly valuable for resource-poor settings.

The report is published today in the journal Nature.

“Our new method provides a way to show, surprisingly quickly, whether there are new transmissible variants of pathogens circulating in populations — and it can be used for a huge range of bacteria and viruses,” said Dr Noémie Lefrancq, first author of the report, who carried out the work at the University of Cambridge’s Department of Genetics.

Lefrancq, who is now based at ETH Zurich, added: “We can even use it to start predicting how new variants are going to take over, which means decisions can quickly be made about how to respond.”

“Our method provides a completely objective way of spotting new strains of disease-causing bugs, by analysing their genetics and how they’re spreading in the population. This means we can rapidly and effectively spot the emergence of new highly transmissible strains,” said Professor Julian Parkhill, a researcher in the University of Cambridge’s Department of Veterinary Medicine who was involved in the study.

Testing the technique

The researchers used their new technique to analyse samples of Bordetella pertussis, the bacteria that causes whooping cough. Many countries are currently experiencing their worst whooping cough outbreaks of the last 25 years. It immediately identified three new variants circulating in the population that had been previously undetected.

“The novel method proves very timely for the agent of whooping cough, which warrants reinforced surveillance, given its current comeback in many countries and the worrying emergence of antimicrobial resistant lineages,” said Professor Sylvain Brisse, Head of the National Reference Center for whooping cough at Institut Pasteur, who provided bioresources and expertise on Bordetella pertussis genomic analyses and epidemiology.

In a second test, they analysed samples of Mycobacterium tuberculosis, the bacteria that causes Tuberculosis. It showed that two variants with resistance to antibiotics are spreading.

“The approach will quickly show which variants of a pathogen are most worrying in terms of the potential to make people ill. This means a vaccine can be specifically targeted against these variants, to make it as effective as possible,” said Professor Henrik Salje in the University of Cambridge’s Department of Genetics, senior author of the report.

He added: “If we see a rapid expansion of an antibiotic-resistant variant, then we could change the antibiotic that’s being prescribed to people infected by it, to try and limit the spread of that variant.”

The researchers say this work is an important piece in the larger jigsaw of any public health response to infectious disease.

A constant threat

Bacteria and viruses that cause disease are constantly evolving to be better and faster at spreading between us. During the COVID pandemic, this led to the emergence of new strains: the original Wuhan strain spread rapidly but was later overtaken by other variants, including Omicron, which evolved from the original and were better at spreading. Underlying this evolution are changes in the genetic make-up of the pathogens.

Pathogens evolve through genetic changes that make them better at spreading. Scientists are particularly worried about genetic changes that allow pathogens to evade our immune system and cause disease despite us being vaccinated against them.

“This work has the potential to become an integral part of infectious disease surveillance systems around the world, and the insights it provides could completely change the way governments respond,” said Salje.

Key findings

• Sensitive cells: Scientists discovered dozens of specific cell types, mostly glial cells, known as brain support cells, that underwent significant gene expression changes with age. Those strongly affected included microglia and border-associated macrophages, oligodendrocytes, tanycytes, and ependymal cells.
• Inflammation and neuron protection: In aging brains, genes associated with inflammation increased in activity while those related to neuronal structure and function decreased.
• Aging hot spot: Scientists discovered a specific hot spot combining both the decrease in neuronal function and the increase in inflammation in the hypothalamus. The most significant gene expression changes were found in cell types near the third ventricle of the hypothalamus, including tanycytes, ependymal cells, and neurons known for their role in food intake, energy homeostasis, metabolism, and how our bodies use nutrients. This points to a possible connection between diet, lifestyle factors, brain aging, and changes that can influence our susceptibility to age-related brain disorders.

“Our hypothesis is that those cell types are getting less efficient at integrating signals from our environment or from things that we’re consuming,” said Kelly Jin, Ph.D., a scientist at the Allen Institute for Brain Science and lead author of the study. “And that loss of efficiency somehow contributes to what we know as aging in the rest of our body. I think that’s pretty amazing, and I think it’s remarkable that we’re able to find those very specific changes with the methods that we’re using.”

To conduct the study, funded by the National Institutes of Health (NIH), researchers used cutting-edge single-cell RNA sequencing and advanced brain-mapping tools developed through NIH’s The BRAIN Initiative® to map over 1.2 million brain cells from young (two months old) and aged (18 months old) mice across 16 broad brain regions. The aged mice are what scientists consider to be the equivalent of a late middle-aged human. Mouse brains share many similarities with human brains in terms of structure, function, genes, and cell types.

“Aging is the most important risk factor for Alzheimer’s disease and many other devastating brain disorders. These results provide a highly detailed map for which brain cells may be most affected by aging,” said Richard J. Hodes, M.D., director of NIH’s National Institute on Aging. “This new map may fundamentally alter the way scientists think about how aging affects the brain and also provides a guide for developing new treatments for aging-related brain diseases.”

A path toward new therapies

Understanding this hot spot in the hypothalamus makes it a focal point for future study. Along with knowing which cells to specifically target, this could lead to the development of age-related therapeutics, helping to preserve function and prevent neurodegenerative disease.

“We want to develop tools that can target those cell types,” said Hongkui Zeng, Ph.D., executive vice president and director of the Allen Institute for Brain Science. “If we improve the function of those cells, will we be able to delay the aging process?”

The latest findings also align with past studies that link aging to metabolic changes as well as research suggesting that intermittent fasting, balanced diet, or calorie restriction can influence or perhaps increase life span.

“It’s not something we directly tested in this study,” said Jin. “But to me, it points to the potential players involved in the process, which I think is a huge deal because this is a very specific, rare population of neurons that express very specific genes that people can develop tools for to target and further study.”

Future brain aging research

This study lays the groundwork for new strategies in diet and therapeutic approaches aimed at maintaining brain health into old age, along with more research on the complexities of advanced aging in the brain. As scientists further explore these connections, research may unlock more specific dietary or drug interventions to combat or slow aging on a cellular level.

“The important thing about our study is that we found the key players — the real key players — and the biological substrates for this process,” said Zeng. “Putting the pieces of this puzzle together, you have to find the right players. It’s a beautiful example of why you need to study the brain and the body at this kind of cell type-specific level. Otherwise, changes happening in specific cell types could be averaged out and undetected if you mix different types of cells together.”

This study was funded by NIH grants R01AG066027 and U19MH114830. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Raman microscopy is a useful technique for imaging biological samples because it can provide chemical information about specific molecules — such as proteins — that take part in the body’s processes. However, the Raman light that comes from biological samples is very weak, so the signal can often get swamped by the background noise, leading to poor images.

The researchers have developed a microscope that can maintain the temperature of previously frozen samples during the acquisition. This has allowed them to produce images that are up to eight times brighter than those previously achieved with Raman microscopy.

“One of the main reasons for blurry images is the motion of the things you’re trying to look at,” explains lead author of the study, Kenta Mizushima. “By imaging frozen samples that were unable to move, we could use longer exposure times without damaging the samples. This led to high signals compared with the background, high resolution, and larger fields of view.” The technique uses no stains and doesn’t require any chemicals to fix the cells in position, so can provide a highly representative view of processes and cell behavior.

The team was also able to confirm that the freezing process conserved the physicochemical states of different proteins. This gives the cryofixing approach a distinct advantage of achieving what the chemical fixing methods cannot.

“Raman microscopy adds a complementary option to the imaging toolbox,” says senior author Katsumasa Fujita. “The fact that it not only provides cell images, but also information about the distribution and particular chemical states of molecules, is very useful when we are continually striving to achieve the most detailed possible understanding.”

The new technique can be combined with other microscopy techniques for detailed analysis of biological samples and is expected to contribute to a wide range of areas in the biological sciences including medicine and pharmaceutics.

Conducted under the supervision of Prof. KWOK Hoi-Sing, Founding Director of the State Key Laboratory of Advanced Displays and Optoelectronics Technologies at HKUST, the study was a collaborative effort with the Southern University of Science and Technology, and the Suzhou Institute of Nanotechnology of the Chinese Academy of Sciences.

A lithography machine is crucial equipment for semiconductor manufacturing, applying short-wavelength ultraviolet light to make integrated circuit chips with various layouts. However, traditional mercury lamps and deep ultraviolet LED light sources have shortcomings such as large device size, low resolution, high energy consumption, low light efficiency, and insufficient optical power density.

To overcome these challenges, the research team built a maskless lithography prototype platform and used it to fabricate the first microLED device by using deep UV microLED with maskless exposure, improving optical extraction efficiency, heat distribution performance, and epitaxial stress relief during the production process.

Prof. KWOK highlighted, “The team achieved key breakthroughs for the first microLED device including high power, high light efficiency, high-resolution pattern display, improved screen performance and fast exposure ability. This deep-UV microLED display chip integrates the ultraviolet light source with the pattern on the mask. It provides sufficient irradiation dose for photoresist exposure in a short time, creating a new path for semiconductor manufacturing.”

“In recent years, the low-cost and high-precision maskless lithography technology of traditional lithography machines has become an R&D hotspot because of its ability to adjust the exposure pattern, provide more diverse customization options, and save the cost of preparing lithography masks. Photoresist-sensitive short-wavelength microLED technology is therefore critical to the independent development of semiconductor equipment,” Prof. KWOK explained.

“Compared with other representative works, our innovation features smaller device size, lower driving voltage, higher external quantum efficiency, higher optical power density, larger array size, and higher display resolution. These key performance enhancements make the study a global leader in all metrics,” Dr. FENG Feng, postdoctoral research fellow at HKUST’s Department of Electronic and Computer Engineering (ECE), concluded.

Their paper, titled “High-Power AlGaN Deep-Ultraviolet Micro-Light-Emitting Diode Displays for Maskless Photolithography,” has been published in the top journal Nature Photonics. It has since earned wide recognition in the industry and was named by the 10th International Forum on Wide Bandgap Semiconductors (IFWS) as one of the top ten advances in China’s third-generation semiconductor technology in 2024.

Looking forward, the team plans to continue enhancing the performance of AlGaN deep ultraviolet microLEDs, improve the prototype, and develop 2k to 8k high-resolution deep ultraviolet microLED display screens.

Dr. FENG is the first author, while Prof. LIU Zhaojun, Adjunct Associate Professor of HKUST’s ECE Department, who concurrently serves as an Associate Professor at Southern University of Science and Technology, is the corresponding author. Team members also include ECE postdoctoral research fellow Dr. LIU Yibo, PhD graduate Dr. ZHANG Ke, and collaborators from other institutions.

Currently, radar systems for automotive and aerospace applications require resolution-enhancement technologies to improve object recognition precision. Achieving this typically involves increasing bandwidth or utilizing ultra-high-resolution algorithms with significant complexity. However, it results in higher costs and increased system complexity.

The research team discovered that additional information embedded in the envelope of radar signals could be used. On that basis, they developed a new algorithm that analyzes the contour features of received signals. This innovative technology improves target differentiation without bandwidth expansion, achieving nearly double the resolution through signal processing on existing radar hardware. In addition, it enables the precise identification of objects both inside and outside the vehicle.

Dr. Bongseok Kim of the DGIST Automotive Technology Division stated, “I am delighted that our work has been published in the IEEE Sensors Journal … We will continue to enhance this technology through follow-up research to enable its practical application in autonomous vehicles and industrial environments.”

Meanwhile, this research was conducted with the support of DGIST’s general project (D-PIC 4.0) and the National Research Foundation of Korea’s Basic Research Support Program. The research results (first author: Dr. Bongseok Kim, DGIST; corresponding author:Dr. Sangdong Kim, DGIST) were published in the IEEE Sensors Journal in December.