Norfolk and Suffolk NHS trust deaths report ‘watered down to spare bosses’

Campaigners slam a report as the BBC reveals drafts were edited to remove leadership criticism.

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Anthony Fauci on the recent spike in Covid cases

Anthony Fauci tells the BBC’s Katty Kay that 96% of the US population has a degree of immunity.

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Saving species from extinction — high-quality kakapo population sequencing provides breakthrough in understanding key conservation genetics

High-quality sequencing of nearly the entire kākāpō population, funded through a Genomics Aotearoa project, is helping New Zealand to manage the health of this critically endangered species.

Not only is it already making a difference to kākāpō survival, but establishing sequencing methods to work with populations under threat is also likely to be the foundation for the future of endangered wildlife science in New Zealand and the rest of the world.

The state-of-the-art methods developed by Dr. Joseph Guhlin (University of Otago ) and an international team to study kākāpō has revealed important aspects of kākāpō biology. The methods, reusable code, and pipeline is a blueprint and tool for conservation genomics in other species, especially intensively managed species. This has massive implications.

Dr. Guhlin’s work over the last year have two very significant outcomes:

  • an in-depth understanding of kākāpō biology that simply would not be possible without genomics
  • high-quality code and reusable pipeline — allowing other researchers to rapidly integrate these methods into their own work — which has significantly advanced New Zealand’s genomic capability.

This has given researchers the tools needed to identify specific genetic characteristics that are crucial to survival.

“Using technology created by Google, we have achieved what is likely the highest quality variant dataset for any endangered species in the world. This dataset is made available, through DOC and Ngai Tahu, for future researchers working with kākāpō,” Dr Guhlin said.

Department of Conservation’s Science Advisor for kākāpō Recovery, Dr. Andrew Digby, believes the genetic tools this study provides will make an immense difference to kākāpō conservation.

“kākāpō suffer from disease and low reproductive output, so by understanding the genetic reasons for these problems, we can now help mitigate them. It gives us the ability to predict things like kākāpō chick growth and susceptibility to disease, which changes our on-the-ground management practices and will help improve survival rates.”

While the study marks the beginning of a new era of kākāpō conservation genetics, Dr Digby acknowledges what it means for the future of all threatened species.

“The Kakapo125+ project is a great example of how genetic data can assist population growth. The novel genetic and machine learning tools developed can be applied to improve the productivity and survival of other taonga under conservation management.”

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Curious and cryptic: New leaf insects discovered

An international research team including the University of Göttingen has described seven previously unknown species of leaf insects, also known as walking leaves. The insects belong to the stick and leaf insect order, which are known for their unusual appearance: they look confusingly similar to parts of plants such as twigs, bark or — in the case of leaf insects — leaves. This sophisticated camouflage provides excellent protection from predators as well as presenting a challenge to researchers. Genetic analysis enabled the researchers to discover “cryptic species,” which cannot be distinguished by their external appearance alone. The findings are not only important for the systematic study of leaf insects, but also for the protection of their diversity. The results were published in the scientific journal ZooKeys.

Taxonomy — meaning the naming, description and classification of species — is difficult in the case of leaf insects: individuals of different species can be difficult to tell apart, yet there can be huge variations within a species. “Individuals of different species are often counted as belonging to the same species based on their appearance. We were only able to identify some of the new species by their genetic characteristics,” explains the Project Lead, Dr Sarah Bank-Aubin, Göttingen University’s Animal Evolution and Biodiversity Department. Some individual insects from India were previously thought to belong to a species that is widespread in Southeast Asia. But now the researchers have found out that they are a completely new species of leaf insects. Bank-Aubin emphasises: “The finding is important for species conservation: if all the individuals die out in India, it is not just a group within a species that is reduced, as was previously thought. In fact, a whole distinct species is being wiped out. This means that the Indian species is particularly important to protect.” Other newly discovered species come from Vietnam, Borneo, Java and the Philippines.

The researchers from Göttingen University worked with leaf insect expert Royce Cumming, City University New York. This research collaboration has led to the identification of over twenty new species. Dr Sven Bradler, who has been researching the evolution of stick and leaf insects at the University of Göttingen for more than 20 years, explains: “There are around 3,500 known species of stick and leaf insects and there are currently just over 100 described species of leaf insect. Although they only make up a small fraction of this diverse family of insects, their spectacular and unexpected appearance makes them unique.”

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Historic red tide event of 2020 fueled by plankton super swimmers

A major red tide event occurred in waters off Southern California in the spring of 2020, resulting in dazzling displays of bioluminescence along the coast. The spectacle was caused by exceedingly high densities of Lingulodinium polyedra (L. polyedra),a plankton species renowned for its ability to emit a neon blue glow. While the red tide captured the public’s attention and made global headlines, the event was also a harmful algal bloom. Toxins were detected at the height of the bloom that had the potential to harm marine life, and dissolved oxygen levels dropped to near-zero as the extreme biomass of the red tide decomposed. This lack of oxygen led to fish die-offs and other destructive impacts on local ecosystems.

Now, for the first time, a study led by scientists at UC San Diego’s Scripps Institution of Oceanography and Jacobs School of Engineering has pinpointed how this plankton species — a dinoflagellate — was able to create such an exceptionally dense bloom. The answer lies in dinoflagellates’ remarkable ability to swim, which lends them a competitive advantage over other species of phytoplankton. According to the authors, this swimming ability can lead to the formation of dense blooms, including those of the bioluminescent variety.

“The idea that vertical swimming gives dinoflagellates a competitive advantage actually goes back more than half a century, but only now do we have the technology to conclusively prove it in the field,” said oceanographer Drew Lucas, senior author of the paper and an associate professor at Scripps Oceanography and the Department of Mechanical and Aerospace Engineering at UC San Diego.

Lucas and former graduate student Bofu Zheng led the work alongside several colleagues in the midst of the red tide event in April and May 2020. The researchers seized the opportunity to deploy sophisticated ocean instruments off the coast of San Diego, resulting in unprecedented measurements. The effort was made possible with funding provided by the Southern California Coastal Ocean Observing System (SCCOOS) through an award by the National Oceanic and Atmospheric Administration (NOAA). The team’s findings were published in the Aug. 28 issue of the Proceedings of the National Academy of Sciences, showcased as the cover story.

The dinoflagellates — L. polyedra specifically — were shown to be highly mobile, swimming upward during the day to photosynthesize and downward at night to access a deep nutrient pool. This resulted in the intensified ruddy coloration of the water at the surface, hence the term “red tide,” seen most prominently in the afternoon. A large population of the dinoflagellates was documented making the downward journey at night, though a portion remained near the surface waters, leading to nighttime displays of bioluminescence. The authors found that this vertical migration is what allowed the dinoflagellates to outgrow their non-mobile competitors, including other species of phytoplankton.

The study validates a 50-year-old hypothesis originally presented by Scripps Oceanography biological oceanographer Richard “Dick” Eppley. He and colleagues posited that the vertical migration of dinoflagellates was linked to harmful algal blooms, which have been documented off Southern California for at least 120 years. Extensive lab research was conducted to support this idea, but it had never been tested in the field until the 2020 event.

As in many dinoflagellate species, L. polyedra is endowed with a pair of flagella — whip-like appendages that propel the single-celled organism through the water. In addition to its ability to swim, L. polyedra is remarkably fast, with a maximum swimming speed of up to 10 body lengths per second for almost 24 hours.

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“In the plankton world, they are Michael Phelps,” said Lucas, describing the dinoflagellates. “For comparison, fast-burst swimming in species like bluefin tuna or shortfin mako is around 9-10 body lengths per second, but only for very short periods. Their exceptional swimming allows L. polyedra to dive to cold depths where they can take up nutrients, allowing these organisms to really bloom and explode in population.”

The team used the Wirewalker — an autonomous, ocean-wave-powered vertical profiling system that was developed at Scripps Oceanography — to continuously measure physical and biochemical conditions from the sea surface to the seafloor, reaching a depth of 100 meters (300 feet). Powered by wave energy, the instrument moves up and down a mooring line attached to a buoy, while taking measurements of temperature, salinity, depth, sunlight levels, chlorophyll fluorescence, and nitrate concentrations. They also captured near-surface images of the bloom using an Imaging FlowCytobot (IFCB), a robotic microscope installed on an offshore mooring; this site is now part of a larger IFCB network overseen by SCCOOS.

Data and images collected by these instruments validated Eppley’s original hypothesis, showing that indeed L. polyedra descended at dusk, reaching a maximum depth of about 30-40 meters (100-130 feet) after 18 to 24 hours of swimming. While in the deep, the dinoflagellates would take up nitrate, which acts as a growth nutrient for plankton, before returning to the surface around noon to photosynthesize during maximum sunlight.

The growth of phytoplankton biomass, or the “bloom,” correlated with proportional decreases in nitrate concentrations at depth, linking the important role that swimming phytoplankton have in the development of certain types of red tides. On cloudy days, the subsurface vertical migration was much less apparent, suggesting that the intensity of sunlight is an important trigger for vertical migration.

Lead author Zheng, now a postdoctoral investigator at Woods Hole Oceanographic Institution (WHOI), was impressed by the many advanced functions of the dinoflagellates, which are comparable in size to the diameter of a human hair.

“These single-celled organisms, namely L. polyedra, are so functionally complex and amazing,” said Zheng. “In addition to their swimming speed, which is far beyond human limits, they can coordinate their behavior according to the day-night cycle by migrating down at night and coming back to the ocean surface during the day; they can produce spectacular bioluminescence; they can photosynthesize; they can even prey on organisms that are smaller than them.”

The researchers also looked at long-term ocean monitoring data captured by the California Cooperative Oceanic Fisheries Investigations (CalCOFI), and long-term mooring data maintained by the Ocean Time-Series Group at Scripps Oceanography to see other consequences from the bloom. Looking at more than 70 years of climate data, the results showed that the bloom created physical and chemical conditions in the water column that deviated from the norm, showing the potential for massive blooms to alter characteristics of the coastal ocean.

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Study co-author and SCCOOS director Clarissa Anderson said this research stands out for its use of novel ocean technologies, which allowed for unparalleled measurements of how phytoplankton respond to small-scale changes in the coastal ocean, as well as calculations of nutrient uptake by dinoflagellates at such fine scales. She also noted the importance of long-term observations as being key to any future efforts to better understand harmful algal blooms.

“The more we understand complex mechanisms that allow a particular species or population of plankton to thrive and persist, the better we can predict runaway events like the 2020 red tide that lasted much longer than theory might dictate,” said Anderson, who is also a biological oceanographer at Scripps Oceanography. “With longer time series of rapid change in coastal nutrient delivery, circulation, light regimes, and algal toxins, we could build more accurate dynamical models for predicting plankton blooms, including those that turn harmful.”

According to the authors, linking phytoplankton behavior and changes in the coastal environment may help researchers better understand the conditions that cause and that arise from harmful algal blooms, aiding in predicting blooms and mitigating their effects.

In addition to Lucas, Zheng, and Anderson, the study was co-authored by Peter Franks, Tamara Schlosser, Uwe Send, and Andrew Barton of Scripps Oceanography; Kristen Davis of the University of California Irvine; and Heidi Sosik of WHOI. Funding for the study was provided by SCCOOS through NOAA awards #NA21NOS0120088 and #NA16NOS0120022.

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Scientists invent new way to sort cells by type using light

Researchers have developed and demonstrated a new method for high-throughput single-cell sorting that uses stimulated Raman spectroscopy rather than the traditional approach of fluorescence-activated cell sorting. The new approach could offer a label-free, nondestructive way to sort cells for a variety of applications, including microbiology, cancer detection and cell therapy.

Jing Zhang from Boston University will present this research at Frontiers in Optics + Laser Science (FiO LS), which will be held 9 — 12 October 2023 at the Greater Tacoma Convention Center in Tacoma (Greater Seattle Area), Washington.

“Our approach (stimulated Raman-activated cell ejection, S-RACE) offers an innovative way to sort cells based on their intracellular chemical composition in a high-throughput manner,” explains Zhang. “Various downstream phenotypic and/or genomic analysis could be applied to the separated cell populations. Furthermore, its compatibility with small cells is advantageous for sorting bacteria and other microorganisms. For example, by employing S-RACE, pathogens or cells exhibiting specific metabolic profiles could be directly captured from their natural habitat, e.g. water bodies, soil, or gastrointestinal tract. Subsequent sequencing enables tasks such as cell taxonomy identification and ecological function assessment.”

Flow cytometry is used in many biomedical fields to rapidly count and characterize various types of cells, including blood cells, stem cells, cancer cells and microorganisms. Sorting cells based on their size, granularity or expression of cell surface and intracellular molecules can be used to gain insights into biological processes or to separate out cells with certain characteristics for additional analysis.

Although most current high-throughput cell sorting methods rely on fluorescence signals for sorting, fluorescence labels can disturb cell function and can’t be used with small molecules. Raman spectroscopy is a promising alternative because it offers label-free and non-destructive single-cell measurement by obtaining a chemical fingerprint of the cell. However, it has been difficult to achieve both a strong Raman signal and a practical microfluidic setup for imaging cells.

In the new work, the researchers describe how they overcame this challenge by using stimulated Raman spectroscopy, which produces a signal several orders of magnitude higher than the more commonly used spontaneous Raman scattering. For sorting, stimulated Raman images are acquired to identify objects or cells of interest, and then 2D galvo mirrors point a 532-nm pulsed laser to the cell. Finally, an acousto-optic modulator is used as a fast pulse picker so that single laser pulses can be used to push the selected cell into the collector. Each ejection takes only about 8 milliseconds.

The researchers first demonstrated their stimulated Raman-activated cell ejection method using a mixture of 1-micron polymer beads, achieving around 95% purity and 98% throughput with about 14 ejections performed each second. They also showed that the method could be used with fixed bacteria.

To apply the sorting method to live yeast cells, the researchers added a thin layer of agar to the ejection module to protect cells from heat and drying and used an agar dish as a collector to provide more cushioning and moisture during cell landing. The researchers used the system to eject approximately 340 yeast cells and observed successful cell growth in the receiving dish after around 40 hours. They also showed that other genomic analysis approaches such as quantitative polymerase chain reaction could be integrated with the sorting approach.

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Unlocking the secrets of cell antennas

The non-specific lethal (NSL) complex is a chromatin-associated factor that has been shown to regulate the expression of thousands of genes in both fruit flies and mammals. Abrogation of the NSL genes leads to the death of the organism, and this phenotype gives rise to this complex’s curious name. Max Planck researchers have now identified the NSL complex as a “master” epigenetic regulator of intraciliary transport genes across multiple cell types and species. The study reveals that this class of genes is “turned on” by the NSL complex irrespective of whether a particular cell has cilia or not. Additionally, the researchers uncovered that this class of cilia-associated genes is in fact vitally important for the function of kidney podocytes, a highly specialized cell type that paradoxically does not carry cilia. These findings have important implications for ciliopathies and kidney disease.

Cilia are thin, eyelash-like extensions on the surface of cells. They perform a wide variety of functions, acting as mechanosensors or chemosensors, and play a crucial role in many signaling pathways. In the last few decades, the organelle has undergone a remarkable, but at the same time sinister, career transformation. It evolved from an organelle whose relevance was unclear to becoming a central player in the pathogenesis of a large group of diseases. These so-called ciliopathies are associated with a wide range of symptoms, including hearing loss, visual impairment, obesity, kidney disease, and mental disability. Different gene mutations impair cilia formation, maintenance, and function, resulting in these ciliopathies, which can sometimes be multi-organ, syndromic disorders.

The proper assembly, maintenance, and function of cilia rely on a process called “intraciliary transport.” Components of the intraciliary transport system “walk” on the microtubule to deliver cargo between the cell body and the ciliary tip to ensure a constant supply of materials. Mutation of genes encoding components within the intraciliary transport machinery could lead to ciliopathies. In their recent study in the journal Science Advances, the lab of Asifa Akhtar identified the NSL complex as a transcriptional regulator of genes known for their roles in the intraciliary transport system of cilia across multiple cell types.

The NSL complex enables intraciliary transport

The NSL complex is a potent epigenetic modifier that regulates thousands of genes in fruit flies, mice, and humans. However, most of the functions of the NSL complex remain mysterious and have only recently begun to be elucidated. “Previous research from our lab indicates that the NSL complex controls many pathways critical for organismal development and cellular homeostasis,” says Asifa Akhtar, Director at the MPI of Immunobiology and Epigenetics in Freiburg.

The complex comprises several proteins and is a histone acetyltransferase (HAT) complex that prepares the genes for activation. “Think of gene regulation as a team effort with different players. One important player is the NSL complex. It puts special marks on the histone proteins on which the DNA is wrapped around in the nucleus, like putting up green flags. These flags tell other regulators to switch on specific genes. We now found that the NSL complex does exactly this for a group of genes linked to moving materials within cilia,” says Tsz Hong Tsang, the first author of the study.

Without components of the NSL complex, the cell cannot build a cilium

The intraciliary transport system is essential because it is needed to build a functional cilium. The cell uses the intraciliary transport system to move material from the cilium base to the growing tip — similar to building a tower. In the study, the researchers used mouse cells to determine the functional consequences of the loss of the NSL complex in the cells.

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They found that fibroblast cells lacking the NSL complex protein KANSL2 could not activate the transport genes nor assemble cilia. “As cilia are the sensory and signaling hubs for cells, loss of KANSL2 leads to the inability of cells to activate the sonic hedgehog signaling pathway, which plays important roles in the regulation of embryonic development, cell differentiation, and maintenance of adult tissues as well as cancer,” says Asifa Akhtar.

Although tiny protrusions, these sensory organelles are incredibly important to cells. Ciliopathies, which affect organs as diverse as the kidney, liver, eye, ear, and central nervous system, remain challenging for biological and clinical studies. The researchers at the Max Planck Institute in Freiburg hope that their analysis of the role of the NSL complex has provided important insights into the regulation of these organelles and the genes associated with them, thus contributing to human health.

Consequences of NSL loss in non-ciliated cells

Cilia are found in most cell types in the human body. This explains why ciliopathies can affect so many different organs and tissues, but there are also cells that are not ciliated. One of the cell types that do not have cilia is mature glomerular podocytes, which are special filtration cells in the kidney. “Interestingly, we found that podocytes also express these intraciliary transport genes that are regulated by the NSL complex. So, we wondered what would happen if they are unable to switch on these genes,” says Tsz Hong Tsang.

The researchers found that in non-ciliated mouse podocytes, the loss of KANSL2 leads to changes in microtubule dynamics in the cells. Microtubules are cytoskeletal components responsible for the mechanical stabilization of the cell and intracellular transport between different organelles. While lacking cilia, mature podocytes have specialized cell processes extending from the cell body called primary and secondary processes, whose functions rely heavily on cytoskeletal components. Although apparently milder than the defect in ciliated cells, the Akhtar lab found that the cytoskeletal defects are likely the cause of severe glomerulopathy and kidney failure observed in mice lacking the NSL complex. These and other extraciliary functions of intraciliary transport genes may help explain the complexity of symptoms presented by ciliopathies.

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How being in space impairs astronauts’ immune system

A new study led by researchers at Karolinska Institutet in Sweden has examined how T cells of the immune system are affected by weightlessness. The results, which are published in the journal Science Advances, could explain why astronauts’ T cells become less active and less effective at fighting infection.

The next steps in the exploration of space are human missions to the moon and to Mars. Space is an extremely hostile environment that poses threats to human health. One such threat is changes to the immune system that occur in astronauts while in space and that persist after their return to Earth. This immune deficiency can leave them more vulnerable to infection and lead to the reactivation of latent viruses in the body.

“If astronauts are to be able to undergo safe space missions, we need to understand how their immune systems are affected and try to find ways to counter harmful changes to it,” says study leader Lisa Westerberg, principal researcher at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet. “We’ve now been able to investigate what happens to T cells, which are a key component of the immune system, when exposed to weightless conditions.”

In the study, the researchers have tried to simulate weightlessness in space using a method called dry immersion. This involves a custom-made waterbed that tricks the body into thinking it is in a weightless state. The researchers examined T cells in the blood of eight healthy individuals for three weeks of exposure to simulated weightlessness. Blood analyses were performed before the experiment started, at 7, 14 and 21 days after the start, and at 7 days after the experiment ended.

They found that the T cells significantly changed their gene expression — that is to say, which genes were active and which were not — after 7 and 14 days of weightlessness and that the cells became more immature in their genetic programme. The greatest effect was seen after 14 days.

“The T cells began to resemble more so-called naïve T cells, which have not yet encountered any intruders. This could mean that they take longer to be activated and thus become less effective at fighting tumour cells and infections. Our results can pave the way for new treatments that reverse these changes to the immune cells’ genetic programme,” says Carlos Gallardo Dodd, PhD student at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet and shared first author with researchers Christian Oertlin and Julien Record at the same department.

After 21 days, the T cells had “adapted” their gene expression to weightlessness so that it had almost returned to normal, but analyses carried out seven days after the experiment ended showed that the cells had regained some of the changes.

The researchers now plan to use Esrange Space Centre’s sounding rocket platform in Kiruna, Sweden, to study how T cells behave in weightless conditions and how their function is affected.

The study was financed by the Swedish National Space Agency, the Swedish Research Council and Karolinska Institutet and was conducted in close collaboration with Claudia Kutter’s research group at Karolinska Institutet/SciLifeLab and collaboration partners at IBMP Moscow and New York University Abu Dhabi. There are no reported conflicts of interest.

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Tiny magnetic beads produce an optical signal that could be used to quickly detect pathogens

Getting results from a blood test can take anywhere from one day to a week, depending on what a test is targeting. The same goes for tests of water pollution and food contamination. And in most cases, the wait time has to do with time-consuming steps in sample processing and analysis.

Now, MIT engineers have identified a new optical signature in a widely used class of magnetic beads, which could be used to quickly detect contaminants in a variety of diagnostic tests. For example, the team showed the signature could be used to detect signs of the food contaminant Salmonella.

The so-called Dynabeads are microscopic magnetic beads that can be coated with antibodies that bind to target molecules, such as a specific pathogen. Dynabeads are typically used in experiments in which they are mixed into solutions to capture molecules of interest. But from there, scientists have to take additional, time-consuming steps to confirm that the molecules are indeed present and bound to the beads.

The MIT team found a faster way to confirm the presence of Dynabead-bound pathogens, using optics, specifically, Raman spectroscopy. This optical technique identifies specific molecules based on their “Raman signature,” or the unique way in which a molecule scatters light.

The researchers found that Dynabeads have an unusually strong Raman signature that can be easily detected, much like a fluorescent tag. This signature, they found, can act as a “reporter.” If detected, the signal can serve as a quick confirmation, within less than an hour, that a target pathogen is indeed present in a given sample. The team is currently working to develop a portable device for quickly detecting a range of bacterial pathogens, and has reported their results today in a special issue of the Journal of Raman Spectroscopy.

“This technique would be useful in a situation where a doctor is trying to narrow down the source of an infection in order to better inform antibiotic prescription, as well as for the detection of known pathogens in food and water,” says study co-author Marissa McDonald, a graduate student in the Harvard-MIT Program in Health Sciences and Technology. “Additionally, we hope this approach will eventually lead to expanded access to advanced diagnostics in resource-limited environments.”

Study co-authors at MIT include Postdoctoral Associate Jongwan Lee; Visiting Scholar Nikiwe Mhlanga; Research Scientist Jeon Woong Kang; Tata Professor Rohit Karnik, who is also the associate director of the Abdul Latif Jameel Water and Food Systems Lab; and Assistant Professor Loza Tadesse of the Department of Mechanical Engineering.

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Oil and water

Looking for diseased cells and pathogens in fluid samples is an exercise in patience.

“It’s kind of a needle-in-a-haystack problem,” Tadesse says.

The numbers present are so small that they must be grown in controlled environments to sufficient numbers, and their cultures stained, then studied under a microscope. The entire process can take several days to a week to yield a confident positive or negative result.

Both Karnik and Tadesse’s labs have independently been developing techniques to speed up various parts of the pathogen testing process and make the process portable, using Dynabeads.

Dynabeads are commercially available microscopic beads made from a magnetic iron core and a polymer shell that can be coated with antibodies. The surface antibodies act as hooks to bind specific target molecules. When mixed with a fluid, such as a vial of blood or water, any molecules present will glom onto the Dynabeads. Using a magnet, scientists can gently coax the beads to the bottom of a vial and filter them out of a solution. Karnik’s lab is investigating ways to then further separate the beads into those that are bound to a target molecule, and those that are not. “Still, the challenge is, how do we know that we have what we’re looking for?” Tadesse says.

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The beads themselves are not visible by eye. That’s where Tadesse’s work comes in. Her lab uses Raman spectroscopy as a way to “fingerprint” pathogens. She has found that different cell types scatter light in unique ways that can be used as a signature to identify them.

In the team’s new work, she and her colleagues found that Dynabeads also have a unique and strong Raman signature that can act as a surprisingly clear beacon.

“We were initially seeking to identify the signatures of bacteria, but the signature of the Dynabeads was actually very strong,” Tadesse says. “We realized this signal could be a means of reporting to you whether you have that bacteria or not.”

Testing beacon

As a practical demonstration, the researchers mixed Dynabeads into vials of water contaminated with Salmonella. They then magnetically isolated these beads onto microscope slides and measured the way light scattered through the fluid when exposed to laser light. Within half a second, they quickly detected the Dynabeads’ Raman signature — a confirmation that bound Dynabeads, and by inference, Salmonella, were present in the fluid.

“This is something that can be used to rapidly give a positive or negative answer: Is there a contaminant or not?” Tadesse says. “Because even a handful of pathogens can cause clinical symptoms.”

The team’s new technique is significantly faster than conventional methods and uses elements that could be adapted into smaller, more portable forms — a goal that the researchers are currently working toward. The approach is also highly versatile.

“Salmonella is the proof of concept,” Tadesse says. “You could purchase Dynabeads with E.coli antibodies, and the same thing would happen: It would bind to the bacteria, and we’d be able to detect the Dynabead signature because the signal is super strong.”

The team is particularly keen to apply the test to conditions such as sepsis, where time is of the essence, and where pathogens that trigger the condition are not rapidly detected using conventional lab tests.

“There are a lot cases, like in sepsis, where pathogenic cells cannot always be grown on a plate,” says Lee, a member of Karnik’s lab. “In that case, our technique could rapidly detect these pathogens.”

This research was supported, in part, by the MIT Laser Biomedical Research Center, the National Cancer Institute, and the Abdul Latif Jameel Water and Food Systems Lab at MIT.

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Cluster of slightly unhealthy traits linked with earlier heart attack and stroke

Middle-aged adults with three or more unhealthy traits including slightly high waist circumference, blood pressure, cholesterol and glucose have heart attacks and strokes two years earlier than their peers, according to research presented at ESC Congress 2023.1

“Many people in their 40s and 50s have a bit of fat around the middle and marginally elevated blood pressure, cholesterol or glucose but feel generally well, are unaware of the risks and do not seek medical advice,” said study author Dr. Lena Lönnberg of Västmanland County Hospital, Västerås, Sweden. “This scenario, called metabolic syndrome, is a growing problem in Western populations where people are unknowingly storing up problems for later in life. This is a huge missed opportunity to intervene before heart attacks and strokes that could have been avoided occur.”

It is estimated that up to 31% of the global population has metabolic syndrome.2 Previous studies have shown that people with metabolic syndrome are at higher risk of diabetes, heart disease, stroke and premature death.3-5 This study investigated the link between asymptomatic metabolic syndrome in midlife and cardiovascular disease and death up to three decades later.

The study enrolled 34,269 adults in their 40s and 50s who attended a cardiovascular screening programme in 1990 to 1999 in the Swedish county of Västmanland. Participants went to their primary health care centre for a clinical examination by a nurse, which included measurements of height, weight, blood pressure, total cholesterol, blood glucose, and waist and hip circumference. They also completed a questionnaire about lifestyle habits, previous history of cardiovascular disease and diabetes, and socioeconomic factors such as education.

Individuals were classified as having metabolic syndrome if they had three or more of the following: 1) waist circumference of 102 cm or above for men and 88 cm or above for women, 2) total cholesterol 6.1 mmol/l or above, 3) 130 mmHg or higher systolic blood pressure and/or 85 mm Hg or higher diastolic blood pressure, 4) fasting plasma glucose 5.6 mmol/l or higher.

Participants with metabolic syndrome were matched for age, sex and date of health examination to two individuals without metabolic syndrome who served as controls. Data on cardiovascular events (myocardial infarction and stroke) and death were collected from national and local registers. The researchers analysed the associations between midlife metabolic syndrome and nonfatal cardiovascular events and all-cause mortality after adjusting for age, sex, smoking, physical inactivity, education level, body mass index, hip circumference and living alone or with family.

A total of 5,084 individuals (15%) met the criteria for metabolic syndrome and a control group of 10,168 individuals without metabolic syndrome was identified. Some 47% of participants were women. During a median follow-up of 27 years, 1,317 (26%) participants with metabolic syndrome died compared with 1,904 (19%) controls — meaning that those with metabolic syndrome were 30% more likely to die during follow-up than their counterparts without metabolic syndrome.

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Non-fatal cardiovascular events (myocardial infarction and/or stroke) occurred in 1,645 (32%) participants with metabolic syndrome and 2,321 (22%) controls — corresponding to a 35% greater risk of heart attack and stroke in the metabolic syndrome group. The median time to the first non-fatal heart attack or stroke was 16.8 years in the metabolic syndrome group and 19.1 years in the control group — a 2.3 year difference.

Dr. Lönnberg said: “As metabolic syndrome is a cluster of risk factors, the level of each individual component does not have to be severely raised. In fact, most people live with slightly raised levels for many years before having symptoms that lead them to seek health care. In our study, middle-aged adults with metabolic syndrome had a heart attack or stroke 2.3 years earlier than those without the collection of unhealthy traits. Blood pressure was the riskiest component, particularly for women in their 40s, highlighting the value of keeping it under control.”

She concluded: “The results underline the importance of early detection of risk factors through health screening programmes so that preventive actions can be taken to prevent heart attack, stroke and premature death. As a general rule of thumb, even if you feel well, check your blood pressure every year, avoid smoking, keep an eye on your waist circumference and last, but definitely not least, be physically active every day.”

Notes

1The abstract “Early screening for metabolic syndrome opens a window of opportunity learnings from a long-term, population-based study” will be presented during the session Risk factors and prevention: epidemiology (2) which takes place on Friday 25 August from 09:15 to 10:00 CEST at Station 10.

2Noubiap JJ, Nansseu JR, Lontchi-Yimagou E, et al. Geographic distribution of metabolic syndrome and its components in the general adult population: A meta-analysis of global data from 28 million individuals. Diabetes Res Clin Pract. 2022;188:109924.

3Lind L, Sundström J, Ärnlöv J, et al. A longitudinal study over 40 years to study the metabolic syndrome as a risk factor for cardiovascular diseases. Sci Rep. 2021;11:2978.

4Lakka HM, Laaksonen DE, Lakka TA, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA. 2002;288:2709-2716.

5Ford ES. Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence. Diabetes Care. 2005;28:1769-1778.

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