Publisher Health

Researchers have successfully engineered human immune cells to model an infection common among immunocompromised people in a breakthrough discovery, paving the way for new drug testing and treatments.
The research, led by the Murdoch Children’s Research Institute and published in Stem Cell Reports, used cutting edge stem cell technology to better understand how the infection invades immune cells and causes health complications, such as lung and skin and soft tissue infections, in immunocompromised people, particularly those with cystic fibrosis.
Murdoch Children’s researcher Dr Shicheng Jacky Sun said the immune cell type the team created in the lab, known as a macrophage, played an important role in infection, inflammation and regeneration. But due to this function was also a natural host for germs.
“Using our stem cell-made immune cells, we successfully infected them with a germ called mycobacteria. We could see where these mycobacteria live inside human immune cells and the immune reactions they triggered,” he said.
“We were also able to use our stem cell model to rapidly test and screen different types of antibiotics against mycobacterium.”
Murdoch Children’s researcher Dr Sohinee Sarkar said the search for effective treatments had been hampered until now by the lack of infection models to test new drugs.

In a series of articles published in the journal Nature Genetics, researchers used data from the SPARK (Simons Powering Autism Research) research cohort, which was created to advance our understanding of the complex genetics of autism and includes genetic data from nearly 43,000 people with autism. The findings show differences in genetic influences among people all along the autism spectrum.
“Autism is a spectrum, and includes individuals with profound autism who often have cognitive differences and/or epilepsy, as well as individuals who are talented and exceptional, often in specific areas. We are now appreciating that the genetic contributions to different phenotypes vary in terms of the genes involved; when those genes are activated during brain development; and how common some of the genetic variants are in the population,” said Wendy Chung, M.D., Ph.D., principal investigator of SPARK.
One study, “Integrating de novo and inherited variants in 42,607 autism cases identifies mutations in new moderate effect genes,” was published in Nature Genetics on August 18, 2022. Researchers analyzed the DNA of almost 43,000 people with autism, including 35,000 participants from the SPARK autism research study, as part of SPARK’s ongoing effort to understand the full spectrum of autism genetics. This largest-ever autism cohort allowed researchers to identify a group of novel “moderate-effect” genes that tend to contribute to autism through inherited variants.
It is widely known that autism is heritable, but previous studies have primarily identified autism genes with de novo variants (DNV) — variants that occur spontaneously in germ cells prior to conception — that are not inherited. Most of these variants are also implicated in other neurodevelopmental disorders (NDDs). Most genetic variants of this type associated with autism have profound effects on the brain in those individuals when they occur. However, only 20 percent of individuals with autism have this type of genetic variant.
“For many years, we have known from twin studies that there must be inherited genetic variants that lead to autism, but we have not been able to systematically identify individual genes until now,” said lead author Pamela Feliciano, Ph.D., SPARK’s scientific director. “We have now identified a group of genes associated with autism, that can include inherited variants, which begin to explain a different part of the autism spectrum.”
To gain a better understanding of the full spectrum of autism genes, the researchers analyzed 19,843 participants with autism, along with one or both of their biological parents, and found that roughly 20 percent of people with autism have de novo genetic variants that affect the function of the associated gene. Nearly 70 percent of this genetic contribution can be attributed to known autism or neurodevelopmental disorder genes. However, this means that although known autism-associated genes are responsible for the majority of de novo variants, there are others still to be identified.

T cells are our immune system’s customised tools for fighting infectious diseases and tumour cells. On their surface, these special white blood cells carry a receptor that recognises antigens. With the help of cryo-electron microscopy, biochemists and structural biologists from Goethe University Frankfurt, in collaboration the University of Oxford and the Max Planck Institute of Biophysics, were able to visualise the whole T-cell receptor complex with bound antigen at atomic resolution for the first time. Thereby they have helped us understand a fundamental process which may pave the way for novel therapeutic approaches targeting severe diseases.
The immune system of vertebrates is a powerful weapon against external pathogens and cancerous cells. T cells play a curcial role in this context. They carry a special receptor called the T-cell receptor on their surface that recognises antigens — small protein fragments of bacteria, viruses and infected or cancerous body cells — which are presented by specialised immune complexes. The T-cell receptor is thus largely responsible for distinguishing between “self” and “foreign.” After binding of a suitable antigen to the receptor, a signalling pathway is triggered inside the T cell that “arms” the cell for the respective task. However, how this signalling pathway is activated has remained a mystery until now — despite the fact that the T-cell receptor is one of the most extensively studied receptor protein complexes.
Many surface receptors relay signals into the interior of the cell by changing their spatial structure after ligand binding. This mechanism was so far assumed to also pertain to the T-cell receptor. Researchers led by Lukas Sušac, Christoph Thomas, and Robert Tampé from the Institute of Biochemistry at Goethe University Frankfurt, in collaboration with Simon Davis from the University of Oxford and Gerhard Hummer from the Max Planck Institute of Biophysics, have now succeeded for the first time in visualizing the structure of a membrane-bound T-cell receptor complex with bound antigen. A comparison of the antigen-bound structure captured using cryo-electron microscopy with that of a receptor without antigen provides the first clues to the activation mechanism.
For the structural analysis, the researchers chose a T-cell receptor used in immunotherapy to treat melanoma and which had been optimised for this purpose in several steps in such a way that it binds its antigen as tightly as possible. A particular challenge on the way to structure determination was to isolate the whole antigen receptor assembly consisting of eleven different subunits from the cell membrane. “Until recently, nobody believed that it would be possible at all to extract such a large membrane protein complex in a stable form from the membrane,” says Tampé.
Once they had successfully achieved this, the researchers used a trick to fish those receptors out of the preparation that had survived the process and were still functional: due to the strong interaction between the receptor complex and the antigen, they were able to “fish” one of the most medically important immune receptor complexes. The subsequent images collected at the cryo-electron microscope delivered groundbreaking insights into how the T-cell receptor works, as Tampé summarises: “On the basis of our structural analysis, we were able to show how the T-cell receptor assembles and recognises antigens and hypothesise how signal transduction is triggered after antigen binding.” According to their results, the big surprise is that there is evidently no significant change in the receptor’s spatial structure after antigen binding, as this was practically the same both with and without an antigen.
The remaining question is how antigen binding could instead lead to T-cell activation. The co-receptor CD8 is known to approach the T-cell receptor after antigen binding and to stimulate the transfer of phosphate groups to its intracellular part. The researchers assume that this leads to the formation of structures which exclude enzymes that cleave off phosphate groups (phosphatases). If these phosphatases are missing, the phosphate groups remain stable at the T-cell receptor and can trigger the next step of the signalling cascade. “Our structure is a blueprint for future studies on T-cell activation,” Tampé is convinced. “In addition, it’s an important stimulus for employing the T-cell receptor in a therapeutic context for treating infections, cancer, and autoimmune diseases.”
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Flexible electronics have enabled the design of sensors, actuators, microfluidics and electronics on flexible, conformal and/or stretchable sublayers for wearable, implantable or ingestible applications. However, these devices have very different mechanical and biological properties when compared to human tissue and thus cannot be integrated with the human body.
A team of researchers atTexas A&M University has developed a new class of biomaterial inks that mimic native characteristics of highly conductive human tissue, much like skin, which are essential for the ink to be used in 3D printing.
This biomaterial ink leverages a new class of 2D nanomaterials known as molybdenum disulfide (MoS2). The thin-layered structure of MoS2 contains defect centers to make it chemically active and, combined with modified gelatin to obtain a flexible hydrogel, comparable to the structure of Jell-O.
“The impact of this work is far-reaching in 3D printing,” said Dr. Akhilesh Gaharwar, associate professor in the Department of Biomedical Engineering and Presidential Impact Fellow. “This newly designed hydrogel ink is highly biocompatible and electrically conductive, paving the way for the next generation of wearable and implantable bioelectronics.”
This study was recently published in ACS Nano.
The ink has shear-thinning properties that decrease in viscosity as force increases, so it is solid inside the tube but flows more like a liquid when squeezed, similar to ketchup or toothpaste. The team incorporated these electrically conductive nanomaterials within a modified gelatin to make a hydrogel ink with characteristics that are essential for designing ink conducive to 3D printing.

Many therapeutics for asthma and other obstructive lung diseases target the β2-adrenergic receptor (β2AR), a G protein-coupled receptor (GPCR) that rapidly supports airway relaxation when stimulated. Yet, overuse of these agents is associated with adverse health outcomes, including death, which has limited their utility as frontline therapies.
Now, a mouse model study published in today’s issue of Molecular Cell, from investigators at University Hospitals (UH) and Case Western Reserve University, identifies a novel strategy to isolate the beneficial effects of β2AR stimulation. This suggests a new therapeutic approach to airway diseases as well as numerous other conditions involving the aberrant function of GPCRs.
“Not only is the β2-adrenergic receptor the mainstay for keeping airways open, it’s often studied as a prototype for how GPCRs work, which constitute the targets of 50% of all drugs,” explained Jonathan S. Stamler, MD, President, Harrington Discovery Institute at UH, Robert S. and Sylvia K. Reitman Family Foundation Distinguished Professor of Cardiovascular Innovation, and Professor of Medicine and Biochemistry at UH and Case Western Reserve School of Medicine.
“Our discovery highlights an obvious benefit to asthma and it’s exemplary of what to expect in GPCR regulation. It opens the area for broad-based research in maximizing the therapeutic benefits of GPCRs.”
All GPCRs, including the β2AR, operate via a feedback loop in which the same molecules that the receptors help generate can circle back and turn the receptors “off” or inactivate them. In the new study, the research team reveal nitric oxide to be a key molecule in the β2AR feedback loop, showing that the production of nitric oxide after β2AR stimulation mediates airway relaxation, but overproduction of the molecule also inactivates β2AR, leading to bronchoconstriction.
“If you prevent that feedback, you’re left with a very powerful airway relaxant that before now had not been thought to be that important in airway relaxation,” said Dr. Stamler.
The study also demonstrates that mice harboring a specific mutation in the β2AR gene that prevents nitric oxide from binding to and inactivating the receptor are resistant to bronchoconstriction, inflammation, and asthma.
Other GPCR receptors shown in the study to be regulated by nitric oxide-based protein modification include the β1 adrenergic receptor and the angiotensin II receptor 1.
“Nitric oxide should be thought of as a key new player in how this class of receptors works,” Dr. Stamler added. “It’s responsible for both the beneficial effects of the receptors and for turning them off. And if you can understand how they’re being turned off — how that nitric oxide is popping on to the receptor — and you can block that, you’re going to be left with a new pathway for opening airways. The next step in our research will focus on leveraging this new pathway therapeutically.”
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Swarms of microrobots injected into the human body could unblock internal medical devices and avoid the need for further surgery, according to new research from the University of Essex.
The study is the first-time scientists have developed magnetic microrobotics to remove deposits in shunts — common internal medical devices used to treat a variety of conditions by draining excess fluid from organs.
Shunts are prone to malfunctioning, often caused by blockages due to a build-up of sediment. The sediment not only narrows and obstructs liquid passing through the shunt, but it also affects the shunt’s flexibility. This leads to patients needing repeated, invasive surgeries throughout their lives either to replace the shunt or use a catheter to remove the blockage.
However, this new research, led by microrobotics expert Dr Ali Hoshiar, from Essex’s School of Computer Science and Electronic Engineering, has shown there could be a wireless, non-invasive alternative to clearing the blockage in a shunt.
Published in the IEEE Transaction on Biomedical Engineering journal, Dr Hoshiar and his team have shown that a swarm of hundreds of microrobots — made of nano size magnetic nanoparticles — injected into the shunt could remove the sediment instead.
“Once the magnetic microrobots are injected into the shunt they can be moved along the tube to the affected area using a magnetic field, generated by a powerful magnet on the body’s surface,” explained Dr Hoshiar. “The swarm of microrobots can then be moved so they scrape away the sediment, clearing the tube.
“The non-invasive nature of this method is a considerable advantage to existing methods as it will potentially eliminate the risk of surgery and a surgery-related infection, thereby decreasing recovery time.”
With each microrobot smaller than the width of a human hair, once the swarm has done its job, it can either be guided to the stomach via a magnetic field or bodily fluid, so they leave the body naturally. Because the microrobots have very high biocompatibility they will not cause toxicity.
The research also found a direct relation between the strength of the magnetic field and the success of scraping away the sediment in the shunt.
This is the first proof-of-concept experiment using microswarms for opening a blockage in a shunt. The next stage of this research is to work with clinicians to carry out trials. The researchers are also looking at how the concept can be used to other applications.
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Men at the highest risk for prostate cancer could be fast-tracked for investigation if their genetic risk was considered in general practice, new research has concluded.
A large-scale study by the University of Exeter, published in the British Journal of Cancer, looked at the impact of incorporating genetic risk for cancer into the GP triage and referral processes. The research concluded that considering genetic risk could improve referrals for those in need — and importantly, avoid invasive biopsy investigations for those at low risk of cancer. Assessing genetic risk in primary care could lead to earlier diagnosis for men most at risk of prostate cancer.
Prostate cancer accounts for around a quarter of new cancer cases in men — approximately 52,000 men are diagnosed per year in the UK alone. It is the second most common cause of cancer death in men in the UK, and five-year survival doubles if it’s diagnosed at an early stage compared to advanced stage. Symptoms are common and easily misdiagnosed, and an estimated 14 per cent of prostate cancer deaths could be avoided if they were diagnosed earlier.
GPs make around 800,000 suspected prostate cancer referrals annually in the UK. The research team estimate that incorporating genetic risk for cancer into GP triage could mean 160,000 men could be expedited for faster investigation, while 320,000 of these could safely avoid referral and unpleasant investigation.
Lead author Dr Harry Green, independent Research Fellow at the University of Exeter Medical School, said: “Our study is the first to demonstrate that incorporating genetic risk into GP’s risk assessment of patients’ symptoms of possible prostate cancer could result in faster referral for those at most risk.”
At the moment, a prostate Specific Antigen (PSA) test is used to investigate men with erectile dysfunction or urination problems, but the accuracy of the test is unclear, and false positive results are common. Only one in three men with a positive PSA test have cancer. An invasive and unpleasant biopsy is often needed for diagnosis. Research shows the PSA test can miss around 15 per cent of cancers.

Severe breathlessness in COVID patients with co-morbidities should be used as a signal for quicker referral for palliative care to help manage their symptoms sooner, new research has found.
A study led by King’s College London shows that symptoms including having moderate to severe breathlessness, agitation and?more than one pre-existing health condition are all associated with shorter survival of COVID and should therefore be used as triggers to prioritise future referrals.
Researchers from King’s Florence Nightingale Faculty of Nursing, Midwifery & Palliative Care and collaborators from the University of York, Hull York Medical School and University of Lancaster, analysed demographic, clinical, outcome, and survival data from patients across 25 centres in England and Wales during the pandemic in 2020 and 2021 to assess changes in symptoms among people with COVID who receive palliative care and determine which treatments are most effective.
They examined symptom severity at three stages — at the point of referral to palliative care, at patients’ first COVID assessment, and at three follow-up assessments — and found the most common symptoms were breathlessness, weakness and lack of energy, drowsiness, anxiety, agitation, confusion/delirium, and pain.
Of the 572 patients included in the study, of which the average age was 77 years-old, 87% were newly referred to palliative care with COVID, while 13% were already supported by palliative care when they contracted the virus.
Once they had been referred, symptoms of COVID were shown to improve quickly for all patients. The average time spent in palliative care was 46 hours. However, those who were newly referred did not survive for as long as those who were already being supported by palliative care.
Professor Irene Higginson, Professor of Palliative Care and Policy and lead researcher said: “This research shows the important role of palliative care for people who have underlying health conditions and worsening COVID.
“The symptom of worsening breathlessness could be a more time-effective trigger for referral to palliative care that helps doctors and nurses identify patients who require the support sooner.
“This would improve people’s symptoms and quality of life. There is no evidence that their length of life would be affected, so it seems like a sensible step to take.”
The research also found that COVID patients receiving palliative care have an average of two other health conditions such as diabetes, high blood pressure, heart disease, dementia, and cancer, and the most common treatments used include low dose morphine and midazolam (a type of sedative), and a regular dose of opioids.
The paper “Symptom control and survival for people severely ill with COVID: A multicentre cohort study” has been published in the Journal of Pain and Symptom Management.
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A review of the latest research highlights the most reported symptoms of various cardiovascular diseases (CVDs), noting that men and women often experience different symptoms, according to a new American Heart Association scientific statement published today in the Association’s flagship peer-reviewed journal, Circulation.
The statement also highlights how symptoms are experienced over time, which may be months or years apart depending on the condition, and on a spectrum of severity or intensity, noting the long-term nature of cardiovascular disease development. The scientific statement writing committee reviewed current research on the symptoms of different cardiovascular diseases. They found that symptoms vary over time and by sex.
Cardiovascular disease is the leading cause of death in the U.S. and around the world. It comprises several conditions, including 6 reviewed in this scientific statement: heart attack, heart failure, valve disease, stroke, heart rhythm disorders, and peripheral artery and vein disease.
“Symptoms of these cardiovascular diseases can profoundly affect quality of life, and a clear understanding of them is critical for effective diagnosis and treatment decisions. The scientific statement is a ‘state of the science’ compendium detailing the symptoms associated with CVD, similarities or differences in symptoms among the conditions, and sex differences in symptom presentation and reporting,” said Chair of the scientific statement writing committee Corrine Y. Jurgens, Ph.D., R.N., A.N.P., FAHA, an associate professor at Boston College’s Connell School of Nursing.
Measuring symptoms — what is important?
Due to their subjectivity, measuring symptoms is difficult. Symptoms may go unrecognized or unreported if people don’t think they are important or related to an existing health condition. In addition, symptoms may occur without changes in disease progression, and disease state may also progress without symptoms.

Researchers at the University of British Columbia have discovered a key vulnerability across all major variants of the SARS-CoV-2 virus, including the recently emerged BA.1 and BA.2 Omicron subvariants.
The weakness can be targeted by neutralizing antibodies, potentially paving the way for treatments that would be universally effective across variants.
The findings, published today in Nature Communications, use cryo-electron microscopy (cryo-EM) to reveal the atomic-level structure of the vulnerable spot on the virus’ spike protein, known as an epitope. The paper further describes an antibody fragment called VH Ab6 that is able to attach to this site and neutralize each major variant.
“This is a highly adaptable virus that has evolved to evade most existing antibody treatments, as well as much of the immunity conferred by vaccines and natural infection,” says Dr. Sriram Subramaniam (he/him), a professor at UBC’s faculty of medicine and the study’s senior author. “This study reveals a weak spot that is largely unchanged across variants and can be neutralized by an antibody fragment. It sets the stage for the design of pan-variant treatments that could potentially help a lot of vulnerable people.”
Identifying COVID-19 master keys
Antibodies are naturally produced by our bodies to fight infection, but can also be made in a laboratory and administered to patients as a treatment. While several antibody treatments have been developed for COVID-19, their effectiveness has waned in the face of highly-mutated variants like Omicron.