Scientists studying the virus’s continuing evolution, and the body’s immune responses, hope to head off a resurgence and to better understand long Covid.Rat droppings from New York City. Poop from dog parks in Wisconsin. Human waste from a Missouri hospital. These are some of the materials that are readying us for the next chapter of the coronavirus saga.More than four years into the pandemic, the virus has loosened its hold on most people’s bodies and minds. But a new variant better able to dodge our immune defenses may yet appear, derailing a hard-won return to normalcy.Scientists around the country are watching for the first signs.“We’re not in the acute phases of a pandemic anymore, and I think it’s understandable and probably a good thing” that most people, including scientists, have returned to their prepandemic lives, said Jesse Bloom, an evolutionary biologist at the Fred Hutchinson Cancer Center in Seattle.“That said, the virus is still evolving, it’s still infecting large numbers of people,” he added. “We need to keep tracking this.”Dr. Bloom and other researchers are trying to understand how the coronavirus behaves and evolves as populations amass immunity. Other teams are probing the body’s response to the infection, including the complex syndrome called long Covid.And some scientists have taken on an increasingly difficult task: estimating vaccine effectiveness in a crowded respiratory milieu.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

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Published8 hours agoShareclose panelShare pageCopy linkAbout sharingBy Fergus WalshMedical editor Thousands of patients in England with suspected lung cancer are being offered a blood test which can show if they can get early access to targeted therapies.The test looks for genetic variations to aid treatment decisions.Some tumours can be treated with pills rather than standard chemotherapy, often meaning fewer side effects. Lung cancer patient Kat Robinson, 33, was able to take tablets at home rather get treatment in hospital, giving her more precious time with her daughter.Kat says she has been told she has at least one year to live, but perhaps several more.She is among 2,000 patients who had already had the test when they presented with cancer symptoms. Lung cancer: Liquid biopsies could speed up treatmentA further 10,000 patients with suspected lung cancer will be offered it across 80 NHS Trusts in England over the next year.Kat’s symptoms began with a headache which wouldn’t go away. After two weeks, her sister persuaded her to see a doctor. “I thought it was a migraine, but my GP said you need to go to hospital right away. I immediately had an MRI and CT, and within two hours of stepping into the hospital I was talking to an oncology doctor.”They found seven tumours in my brain, which were causing my headaches, but further investigation found that my primary cancer was in my lung, where I have three tumours.”The cancer had also spread to Kat’s lymph nodes and her skull. She was offered a blood test, also described as a “liquid biopsy” which looks for fragments of DNA which have broken off tumours and are in the bloodstream. This so-called “circulating tumour DNA” revealed that Kat’s cancer growth was being driven by a mutation in the ALK gene. Although uncommon, the mutation is often seen in younger patients with non-small cell lung cancer who, like Kat, are non-smokers. It meant the best treatment for her was a targeted drug called brigatinib.”They were preparing me for radiotherapy and then chemotherapy, but instead I was able to go on this daily tablet.” She says she has had very few side effects, apart from nausea.Kat, from Dorset, decided to be completely candid with her 11-year-old daughter Paige about her cancer: “We talk about pretty much everything, and she has just tackled it head-on.”Paige says that before the diagnosis, her mother was very focused on her job as an accountant, but now she always has time for her. She says: “It has taught me that family is all that matters. I have learned how to cook loads of meals, and we are trying to build as many memories as we can.”Kat says when brigatinib stops working, doctors have said there is another targeted drug she can take before requiring radiotherapy and chemotherapy.The family has set up a gofundme page to help raise £10,000 so that Kat can take her daughter to Disney World in Florida. Brigatinib has a list price of more than £5,000 a month, but the NHS has negotiated a confidential discount with the manufacturer Takeda. Patient blood tests from across England will be analysed in a laboratory at the Royal Marsden Hospital in Sutton, Surrey, with the aim of turning around the results within 14 days.Prof Sanjay Popat, consultant clinical oncologist at the Marsden, says the use of the blood test is a “superb idea” and means patients have faster access to the right treatment for their cancer.He says brigatinib is one of eight targeted treatments for non-small cell lung cancer, which accounts for at least 80% of lung cancer cases. All these drugs are tablets which can be taken at home by patients. “These tablets are highly effective and their side-effect profile is very good. By contrast, chemotherapy is tough – it makes people tired, and can cause nausea and hair loss.”He says the longer term outlook for patients is improving. “In the pre-targeted drugs era patients with widespread non-small cell lung cancer had an average survival of around a year or even less. We are now seeing survival measured in years.”Prof Popat says the use of blood tests or ‘liquid biopsies’ is likely to broaden to breast cancer and cancers in children.Peter Johnson, National Clinical Director for Cancer at NHS England, says: “The NHS has shown it can lead the way on innovation in cancer diagnosis and treatment, and this pilot is another example of our commitment to getting patients cutting-edge treatments and therapies to improve outcomes, giving people facing lung cancer more precious time with loved ones.” More on this storyBlood-test biopsy could speed up cancer treatmentPublished25 April 2023Escape to the Country’s Jonnie Irwin dies aged 50Published3 FebruaryMy lung cancer was diagnosed after Covid symptomsPublished11 MarchRelated Internet LinksNHS EnglandThe Royal MarsdenThe BBC is not responsible for the content of external sites.

Blood vessels engineered from stem cells could help solve several research and clinical problems, from potentially providing a more comprehensive platform to screen if drug candidates can cross from the blood stream into the brain to developing lab-grown vascular tissue to support heart transplants, according to Penn State researchers. Led by Xiaojun “Lance” Lian, associate professor of biomedical engineering and of biology, the team discovered the specific molecular signals that can efficiently mature nascent stem cells into the endothelial cells that comprise the vessels and regulate exchanges to and from the blood stream.
They published their findings today (March 21) in Stem Cell Reports. The team already holds a patent on foundational method developed 10 years ago and has filed a provisional application for the expanded technology described in this paper.
The researchers found they could achieve up to a 92% endothelial cell conversion rate by applying two proteins — SOX17 and FGF2 — to human pluripotent stem cells. This type of stem cell, which the researchers derived from a federally approved stem cell line, can differentiate into almost any other cell type if provided the right proteins or other biochemical signals. SOX17 and FGF2 engage three markers in stem cells, triggering a growth cascade that not only converts them to endothelial cells but also enables them to form tubular-like vessels in a dish.
The more efficient differentiation and lab-grown vessels could allow researchers to grow an artificial blood brain barrier to test neurological drugs under development, according to Lian. Other eventual clinical uses may include reestablishing vascular structures after heart damage.
“Drugs designed to treat brain diseases need to pass through the blood brain barrier to be effective,” Lian said. The blood brain barrier is a membrane packed with vessels and regulates what can pass from the blood into the brain. “Our cells can form a tight layer in a dish, onto which we could add various chemicals and see how they pass through.”
Next, Lian said, the team will collaborate with industry partners to advance the artificial blood brain barrier and begin testing various drugs. Getting to this point, however, required a decade of investigating the molecular mechanism underpinning how stem cells convert to endothelial cells.
“In 2014, we published a protocol using a small molecule that could help the cells differentiate about 20% of the time, but we’ve now found that just one gene, SOX17, is sufficient for differentiating the about 80% of cells into endothelial cells,” said Lian, associate professor of biomedical engineering and of biology at Penn State. “That was completely unknown.”
In their prior stem cell differentiation process, the low efficiency resulted in heterogenous cell populations, making them difficult to sort and to obtain enough for other research or clinical applications. Lian explained that the researchers knew some of the cells were endothelial cells, but they couldn’t predict the other cell types.

To make more homogenous populations, the researchers examined the proteins at play during the process. They first noticed that cells expressed SOX17 during differentiation, so they removed the cells’ ability to express the protein and analyzed how its absence changed function.
“Before knocking down SOX17 expression, about 20% of stem cells would become endothelial cells,” Lian said “After, differentiation dropped to about 5% at best. We found that SOX17 is required for this process. It was a lucky and surprising finding.”
With the addition of SOX17, 80% of stem cells could differentiate. But the researchers wanted to do better, Lian said. The stem cells produce three markers, but SOX17 only triggers two of them to begin the differentiation process. The third marker, called CD31, doesn’t work when only exposed to SOX17.
“That was a problem for us. We spent two to three years figuring out why,” Lian said, explaining that another protein, called FGF2 could induce the marker without affecting SOX17’s influence on the other two markers. The combination results in up to 92% of the stem cells differentiating into endothelial cells — a more than 350% increase in efficiency from the researchers’ original approach. “Sometimes science is very difficult, but we do not give up.”
With all three markers activated, the differentiated cells can form tubular-like vessels in a dish. They can also uptake proteins, like blood vessels in the body. The researchers tested this ability by inducing inflammation to see if the endothelial cells could detect the protein signal involved — they could.
“Our cells are indeed functional,” Lian said. “With SOX17 and FGF2, we can determine the fate of these stem cells to be precisely what we need.”
Lian is also affiliated with the Materials Research Institute and the Huck Institutes of the Life Sciences at Penn State. Other collaborators on the study include Michael W. Ream, who is a graduate student in the Lian lab in the Department of Biomedical Engineering; Lauren N. Randolph, who earned her doctorate degree in biomedical engineering at Penn State and is now with the San Raffaele Telethon Institute for Gene Therapy in Italy; Yuqian Jian, who also earned her doctoral degree in biomedical engineering at Penn State and is now with the Departments of Pediatrics and of Genetics at Stanford University; and Yun Chang and Xiaoping Bao, both with Purdue University’s Davidson School of Chemical Engineering.
The U.S. National Science Foundation and the National Institutes of Health funded this research.

Identifying genetic variants and the role they play in predisposing people to Alzheimer’s disease can help researchers better understand how to treat the neurodegenerative condition for which there is currently no cure. A new study led by Boston University School of Public Health (BUSPH) and UTHealth Houston School of Public Health has identified several genetic variants that may influence Alzheimer’s disease risk, putting researchers one step closer to uncovering biological pathways to target for future treatment and prevention.
Published in the journal Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, the study utilized whole genome sequencing and identified 17 significant variants associated with Alzheimer’s disease in five genomic regions. This data enables researchers to pinpoint rare and important genes and variants, building upon genome-wide association studies, which focus only on common variants and regions.
The findings underscore the value of whole genome sequencing data in gaining long-sought insight into the ultimate causes and risk factors for Alzheimer’s disease, which is the fifth leading cause of death among people 65 and older in the United States. As the most common form of dementia, Alzheimer’s disease currently affects more than 6 million Americans and that number is expected to skyrocket to nearly13 million by 2050.
“Prior genome-wide association studies using common variants have identified regions of the genome, and sometimes genes, that are associated with Alzheimer’s disease,” says study co-senior author Dr. Anita DeStefano, professor of biostatistics at BUSPH. “Whole genome sequence data interrogates every base pair in the human genome and can provide more information about which specific genetic change in a region may be contributing to Alzheimer’s disease risk or protection.”
For the study, the researchers conducted single variant association analyses and rare variant aggregation association tests using whole genome sequencing data from the Alzheimer’s Disease Sequencing Project (ADSP), a genetics initiative that the National Institutes of Health developed in 2012 as part of the National Alzheimer’s Project Act’s goal to treat and prevent the disease. The ADSP data include more than 95 million variants among 4,567 participants with or without the disease.
Among the 17 significant variants that were linked to Alzheimer’s disease, the KAT8 variant was one of the most notable, as it was associated with the disease in both the single and rare variant analyses. The researchers also found associations with several rare TREM2 variants.
“By using whole genome sequencing in a diverse sample, we were able to not only identify novel genetic variants associated with Alzheimer’s disease risk in known genetic regions, but also characterize whether the known and novel associations are shared across populations,” says study co-lead and corresponding author Dr. Chloé Sarnowski, assistant professor in the Department of Epidemiology at UTHealth Houston School of Public Health.

The ADSP includes ethnically diverse participants, and the population-specific assessments focused on White/European-ancestry, Black/African-American, and Hispanic/Latino subgroups, as well as a multi-population meta-analysis. Historically, Black and and Latino populations have been underrepresented in genetic studies of Alzheimer’s disease despite having a higher prevalence of the disease than other ethnic groups.
“Including participants that represent diverse genetic ancestry and diverse environments in terms of social determinants of health is important to understanding the full spectrum of Alzheimer’s disease risk, as both the prevalence of the disease and the frequencies of genetic variants can differ among populations,” says Dr. DeStefano. The sample sizes in the population-specific analyses were small, so the team had limited ability to detect associations, she says, “but we replicated known population differences for the APOE gene, which is one of the best-known and strongest risk genes for Alzheimer’s disease.”
In future studies, the researchers hope to examine the population-specific variants they identified in much larger sample sizes, as well as explore how these variants affect biological functioning.
“We are currently working on expanding this research to be able to use whole genome sequencing with larger sample sizes in the ADSP to be able to look at the full array of genetic variants, not only within known Alzheimer’s disease genetic regions, but across the whole genome,” says co-senior author Dr. Gina Peloso, associate professor of biostatistics at BUSPH.
The study was also co-led by Yanbing Wang while she was a PhD student in biostatistics at BUSPH. It was funded by the National Institute on Aging under Award Numbers U01 AG058589 and U01 AG068221.

Researchers at the University of Zurich and the University Hospital Zurich have discovered that a specific mutation in the cancer cells of an aggressive type of blood cancer can prevent novel immunotherapies such as CAR T-cell therapy from working. Their study also explains why the cancer cells are resistant and how this resistance can be overcome: through concomitant pharmacotherapy or genetically improved CAR T-cells.
Acute myeloid leukemia (AML) is an aggressive form of blood cancer. It is caused by mutations in a large number of genes that are acquired in the course of a person’s life. One of these genes — the tumor suppressor gene TP53 – plays a key role. Normally, TP53 helps to prevent the development of tumors. Blood cancer patients in whom this gene is mutated, however, face an extremely poor prognosis, as their genes are resistant to conventional chemotherapeutic agents. Intensive research is therefore being carried out into new therapeutic approaches, such as CAR (chimeric antigen receptor) T-cells, which are already being used successfully for other cancers of the blood.
Mutation in blood cancer cells weakens immunotherapy defense cells
An international research team led by Professors Markus Manz and Steffen Boettcher from the University of Zurich (UZH) and the Department of Medical Oncology and Hematology at the University Hospital Zurich (USZ) has now shown that TP53-mutantAML cells are also significantly more resistant to a new type of immunotherapy — CAR T-cell therapy — than AML cells without the mutated gene. “The reason for the poorer effect of CAR T-cells with mutated TP53 is that these immune cells are exhausted more quickly and are therefore less active against the cancer cells,” says Steffen Boettcher, chief of service at USZ.
In CAR T-cell therapy, certain immune cells — the T-cells — are extracted from a patient’s blood. These immune cells are then genetically modified in the lab so that they form numerous new contact points (CARs) on their surface. Reintroduced into the patient, these CAR T-cells are able to recognize certain surface structures on the tumor cells, which enables the CAR T-cells to identify the cancer cells and destroy them in a targeted manner. Various CAR T-cell products are currently being tested against AML in early clinical trials.
Concomitant pharmacotherapies or advanced CAR T-cells are effective against resistant cancer cells
In their study, the researchers not only examined the mechanism underlying the resistance of mutated AML cells to CAR T-cell immunotherapy; they also found out how the endurance of CAR T-cells can be increased and a weak point of TP53-mutant AML cells can be exploited to overcome this resistance. Through additional pharmacological concomitant therapies or further genetic improvement of the CAR T-cells, they were able to drastically increase the effectiveness of CAR T-cells against TP53-mutant AML cells to the point where there was no longer any therapeutic difference compared to non-mutated AML cells.
“This proof-of-principle study shows that concurrent pharmacological therapies and genetically engineered CAR T-cells are promising strategies to develop more effective and tolerable immunotherapies for patients with TP53-mutantAML,” says head of clinic Markus Manz.

Using novel genetic and genomic tools, researchers at the Icahn School of Medicine at Mount Sinai have shed light on the role of immune cells called macrophages in lipid-rich tissues like the brain, advancing our understanding of Alzheimer’s and other diseases. The study, published in the March 6 online issue of Nature Communications, represents a step forward in understanding immune cell regulation and its impact on disease progression.
The researchers initially studied genes controlling macrophages, also referred to as microglia when they are in the brain, particularly in response to damage of fatty tissues like the brain. Disease-associated microglia/macrophages are thought to be protective, as they participate in removing lipid-rich waste derived from tissue damage. Therefore, researchers wanted to find factors that promote the “garbage removal” activity of these cells.
They identified two influential genes, BHLHE40 and BHLHE41, and used advanced gene editing technology (CRISPR-Cas9) to deactivate them in lab-grown cells. These cells were then transformed into microglia. The resulting microglia lacking BHLHE40 and BHLHE41 resembled disease-associated microglia observed in Alzheimer’s disease, showing improved ability to clear cholesterol-rich waste. Confirmation came from experiments on cultured human peripheral macrophages and microglia from mice lacking these genes.
“Through our analysis of single-cell datasets from multiple organs, we’ve uncovered pivotal regulators of immune cell function essential for tissue health,” says senior study author Alison M. Goate, DPhil, the Jean C. and James W. Crystal Professor and Chair of Genetics and Genomic Sciences at Icahn Mount Sinai. “Our use of advanced models has further validated the critical role played by transcription factors BHLHE40 and BHLHE41, proteins that regulate gene expression by binding to specific DNA sequences, in controlling immune cell responses, presenting potential targets for therapeutic intervention.”
Next, the researchers will investigate whether microglia without BHLHE40 and BHLHE41 can help clear away harmful amyloid proteins. In one experiment, the investigators will grow brain cells such as neurons and astrocytes that have harmful Alzheimer’s mutations in a dish and test whether immune cells without BHLHE40 and 41 influence beta-amyloid levels, neurodegeneration, and cytokine response (neuroinflammation). In another, they will inject the immune cells with and without BHLHE40 and 41 into a mouse model of Alzheimer’s to see how they affect the development of Alzheimer’s-like plaques.
“We want to see how these cells, particularly those without the two genes, impact Alzheimer’s-related phenotypes in both dish and mouse models. We predict that in mice, microglia without BHLHE40 and 41 will clear away beta-amyloid plaques more effectively than control microglia that have normal levels of BHLHE40 and 41. Also, we’re exploring how lack of these genes in the brain immune cells affect other types of cells in the brain such as neurons and astrocytes,” says Dr. Goate.
The paper is titled “BHLHE40/41 regulate microglia and peripheral macrophage responses associated with Alzheimer’s disease and other disorders of lipid-rich tissues.”
The remaining authors of the paper, all with Icahn Mount Sinai except where indicated, are: Anna Podlesny-Drabiniok, PhD; Gloriia Novikova, PhD; Yiyuan Liu, PhD; Josefine Dunst, PhD (Anocca in Sweden); Rose Temizer, PhD candidate (National Institute of Mental Health); Samuele Marro, PhD; Taras Kreslavskiy, PhD (Karolinska Institute); and Edoardo Marcora, PhD.
The study was made possible by funding from various sources, including NIH grants (RF1AG054011, U01AG058635, R56AG081417, U01AG066757, NHLBI R01HL153712, S10OD026880 and S10OD030463) and support from The JPB Foundation and BrightFocus Foundation (A2021014F), the New York State Department of Health stem cell biology fellowship (NYSTEM- C32561GG), America Heart Association (20SFRN35210252), and Graduate Women in Science Fellowship.

Aging may be less about specific “aging genes” and more about how long a gene is. Many of the changes associated with aging could be occurring due to decreased expression of long genes, say researchers in an opinion piece publishing March 21 in the journal Trends in Genetics. A decline in the expression of long genes with age has been observed in a wide range of animals, from worms to humans, in various human cell and tissue types, and also in individuals with neurodegenerative disease. Mouse experiments show that the phenomenon can be mitigated via known anti-aging factors, including dietary restriction.
“If you ask me, this is the main cause of systemic aging in the whole body,” says co-author and molecular biologist Jan Hoeijmakers of the Erasmus University Medical Center, Rotterdam; the University of Cologne; and Oncode Institute/Princess Maxima Institute, Utrecht.
The authors span four research groups from Spain, the Netherlands, Germany, and the United States, with each group arriving at the same conclusions using different methods.
Aging is associated with changes at the molecular, cellular, and organ level — from altered protein production to sub-optimal cell metabolism to compromised tissue architecture. These changes are thought to originate from DNA damage resulting from cumulative exposure to harmful agents such as UV radiation or reactive oxygen species generated by our own metabolism.
While a lot of research in aging has focused on specific genes that might accelerate or slow aging, investigations of exactly which genes are more susceptible to aging have revealed no clear pattern in terms of gene function. Instead, susceptibility seems to be linked to the genes’ lengths.
“For a long time, the aging field has been focused on genes associated with aging, but our explanation is that it is much more random — it’s a physical phenomenon related to the length of the genes and not to the specific genes involved or the function of those genes,” says co-author Ander Izeta of the Biogipuzkoa Health Research Institute and Donostia University Hospital, Spain.
It essentially comes down to chance; long genes simply have more potential sites that could be damaged. The researchers compare it to a road trip — the longer the trip, the more likely that something will go wrong. And because some cell types tend to express long genes more than others, these cells are more likely to accumulate DNA damage as they age. Cells that don’t (or very rarely) divide also seem to be more susceptible compared to rapidly replicating cells because long-lived cells have more time to accumulate DNA damage and must rely on DNA repair mechanisms to fix them, whereas rapidly dividing cells tend to be short-lived.

Because neural cells are known to express particularly long genes and are also slow or non-dividing, they are especially susceptible to the phenomenon, and the researchers highlight the link between aging and neurodegeneration. Many of the genes involved in preventing protein aggregation in Alzheimer’s disease are exceptionally long, and pediatric cancer patients, who are cured by DNA-damaging chemotherapy, later suffer from premature aging and neurodegeneration.
The authors speculate that damage to long genes could explain most of the features of aging because it is associated with known aging accelerants and because it can be mitigated with known anti-aging therapies, such as dietary restriction (which has been shown to limit DNA damage).
“Many different things that are known to affect aging seem to lead to this length-dependent regulation, for example, different types of irradiation, smoking, alcohol, diet, and oxidative stress,” says co-author Thomas Stoeger of Northwestern University.
However, although the association between the decline in long-gene expression and aging is strong, causative evidence remains to be demonstrated. “Of course, you never know which came first, the egg or the chicken, but we can see a strong relationship between this phenomenon and many of the well-known hallmarks of aging,” says Izeta.
In future studies, the researchers plan to further investigate the phenomenon’s mechanism and evolutionary implications and to explore its relationship with neurodegeneration.

University of Calgary researchers have discovered the lungs communicate directly with the brain when there is an infection. Findings show the brain plays a critical role in triggering the symptoms of sickness, which may change the way we treat respiratory infections and chronic conditions.
“The lungs are using the same sensors and neurons in the pain pathway to let the brain know there’s an infection,” says Dr. Bryan Yipp, MD ’05, MSc’05, clinician researcher at the Cumming School of Medicine and senior author on the study. “The brain prompts the symptoms associated with sickness; that overall feeling of being unwell, feeling tired and loosing your appetite. The discovery indicates we may have to treat the nervous system as well as the infection.”
Prior to this study, conducted in mice, it was thought infections in the lungs and pneumonia induce inflammatory molecules that eventually made their way to the brain through the blood stream. Sickness was thought to be a consequence of the immune system kicking into action. However, findings reveal that sickness results from nervous system activation in the lung.
Understanding the lung-brain dialogue is important for treatment because bacteria that cause lung infections can produce a biofilm, a coating to surround themselves so the nervous system can’t see them. That allows the bug to hide out in the lungs for a long time, which may shed light across diverse serious lung infections that are less symptomatic. For example, an unexplained anomaly Yipp witnessed in the intensive care unit (ICU) during COVID. The phenomenon, coined “happy hypoxia,” was being recorded in ICUs throughout the world.
“We would have patients whose oxygen levels were extremely low and x-rays confirmed they may need to be put on life support. Yet, when I went to see the patient, they would say I feel fine,” says Yipp. “These people were experiencing limited sickness symptoms even though the virus was aggressively damaging their lungs.”
Yipp says understanding the lung brain communication pathways may also have broad implications for people with chronic lung infections like cystic fibrosis (CF). Many people with CF have a biofilm bacterium in their lungs and are asymptomatic. They feel okay, but then have a flare where they can become very ill. The reason for the flare can’t always be traced.
“It is possible the flare is also neurological that these people live asymptomatically because bacteria are hiding out,” says Yipp.

The findings, published in Cell, are the work of an interdisciplinary team including experts in neurobiology, microbiology, immunology, and infectious disease.
“Physician specialties are usually based on individual organs, with pulmonologists caring for the lungs and neurologists caring for the brain. Our study shows the lung is altering the brain and the brain is altering the organ. This intersection of communication is a different way of thinking about disease,” says Yipp. “It’s all connected to the brain and there are probably even more complex circuits that are happening. We can now think about targeting neurocircuitry along with antibiotics to deal with infections and the sickness they cause.”
University of Calgary researchers Drs. Christophe Altier, PhD, Joe Harrison, PhD, and Deborah Kurrasch, PhD, along with Dr. Jaideep Bains, PhD, Krembil Research Institute, Toronto, are corresponding authors on the study.
The researchers add there was one more unique finding. Male mice were much sicker than the females even though they had the same bacterial infection. Researchers found that male sickness was more dependent on neuronal communications then females. Yipp says this finding could lend credibility to the so-called “man flu,” a colloquial term where men are thought to wildly exaggerate sickness due to respiratory infections. Turns out they may not be exaggerating, after all.

The drug minocycline, an antibiotic that also decreases inflammation, failed to slow vision loss or expansion of geographic atrophy in people with dry age-related macular degeneration (AMD), according to a phase II clinical study at the National Eye Institute (NEI), part of the National Institutes of Health.
Dry AMD affects the macula, the part of the eye’s retina that allows for clear central vision. In people with dry AMD, patches of light-sensing photoreceptors and their nearby support cells begin to die off, leaving regions known as geographic atrophy. Over time, these regions expand, causing people to lose more and more of their central vision. Microglia, immune cells that help maintain tissue and clear up debris, are present at higher levels around damaged retinal regions in people with dry AMD than in people without AMD. Scientists have suggested that inflammation — and particularly microglia — may be driving the expansion of geographic atrophy regions.
This study, led by Tiarnan Keenan, M.D., Ph.D., a Stadtman Tenure-Track Investigator at the NEI’s Division of Epidemiology and Clinical Applications, tested whether inhibiting microglia with minocycline might help slow geographic atrophy expansion and its corresponding vision loss. The trial enrolled 37 participants at the NIH Clinical Center in Bethesda, Maryland, and at the Bristol Eye Hospital, United Kingdom. After a nine-month period where the researchers tracked each participant’s rate of geographic atrophy expansion, the participants took twice-daily doses of minocycline for two years. The researchers compared each participant’s rate of geographic atrophy expansion while taking minocycline to their baseline rate, and found there was no difference in geographic atrophy expansion rate or vision loss with minocycline.
Previous studies have shown that minocycline can help reduce inflammation and microglial activity in the eye, including the retina. The drug has shown beneficial effects for conditions such as diabetic retinopathy, but has not previously been tested for dry AMD.
The clinical study was funded by the NEI Intramural Program, and took place in part at the NIH Clinical Center. Clinical trial number NCT02564978.