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A recent study by Johns Hopkins Medicine researchers provides evidence that CD4+ T lymphocytes — immune system cells also known as helper T cells — produced by people who received either of the two available messenger RNA (mRNA) vaccines for COVID-19 persist six months after vaccination at only slightly reduced levels from two weeks after vaccination and are at significantly higher levels than for those who are unvaccinated.
The researchers also found that the T cells they studied recognize and help protect against the delta variant of SARS-CoV-2, the virus that causes COVID-19. According to the U.S. Centers for Disease Control and Prevention, the delta variant — currently the predominant strain of SARS-CoV-2 in the United States — causes more infections and spreads faster than earlier forms of the virus.
The study findings were first reported online Oct. 25, 2021, in the journal Clinical Infectious Diseases.
“Previous research has suggested that humoral immune response — where the immune system circulates virus-neutralizing antibodies — can drop off at six months after vaccination, whereas our study indicates that cellular immunity — where the immune system directly attacks infected cells — remains strong,” says study senior author Joel Blankson, M.D., Ph.D., professor of medicine at the Johns Hopkins University School of Medicine. “The persistence of these vaccine-elicited T cells, along with the fact that they’re active against the delta variant, has important implications for guiding COVID vaccine development and determining the need for COVID boosters in the future.”
To reach these findings, Blankson and his colleagues obtained blood from 15 study participants (10 men and five women) at three times: prior to vaccination, between seven and14 days after their second Pfizer/BioNTech or Moderna vaccine dose, and six months after vaccination. The median age of the participants was 41 and none had evidence of prior SARS-CoV-2 infection.
CD4+ T lymphocytes get their nickname of helper T cells because they assist another type of immune system cell, the B lymphocyte (B cell), to respond to surface proteins — antigens — on viruses such as SARS-CoV-2. Activated by the CD4+ T cells, immature B cells become either plasma cells that produce antibodies to mark infected cells for disposal from the body or memory cells that “remember” the antigen’s biochemical structure for a faster response to future infections. Therefore, a CD4+ T cell response can serve as a measure of how well the immune system responds to a vaccine and yields humoral immunity.

High or low blood pressure in patients during surgery to repair a spinal cord injury may contribute to poorer outcomes, suggests a study published today in eLife.
The findings suggest that maintaining an optimal blood pressure range during surgery may help patients recover motor function. They also show how machine learning techniques may help scientists answer key clinical questions using real-world data.
Current guidelines for treating patients with spinal cord injuries recommend avoiding low blood pressure, ensuring the adequate flow of blood to the injury site to allow recovery. But blood pressure that is too high can cause bleeding in the spinal cord that can add to the damage.
“The precise window for optimal blood pressure management to promote recovery from acute spinal cord injury is poorly understood,” explains co-first author Abel Torres-Espin, Assistant Professor of Neurological Surgery at the University of California, San Francisco (UCSF), US. “We set out to apply machine learning analytics to blood pressure and heart rate changes in operating rooms. The idea was to test the associations between these factors during surgery and neurorecovery to determine treatment thresholds that forecast recovery.”
Torres-Espin and the interdisciplinary research team analysed blood pressure data from 118 patients who underwent surgery for spinal cord injuries at the Zuckerberg San Francisco General Hospital and the Santa Clara Valley Medical Center.
“We found that patients with blood pressure that was either too high or too low during surgery for an acute spinal cord injury had poorer neuromotor recovery after surgery,” says co-first author Jenny Haefeli, Assistant Professor of Neurological Surgery at UCSF Weill Institute for Neurosciences. The team also found that patients had the best chance at recovery if their mean blood pressure was maintained between 76 mmHg and 104-117mmHg.
The results suggest that more precise upper and lower blood pressure targets may help physicians maximise their patients’ odds of recovering after a spinal cord injury, although these findings need to be confirmed by other studies. But if they are, they could lead to more use of machine learning tools to guide the care of patients with spinal cord injuries.
“Machine learning tools could be used to create real-time models that help predict the likelihood of a patient’s recovery,” concludes senior author Adam Ferguson, Professor of Neurological Surgery at UCSF School of Medicine. “Such models could also be applied to forecasting patient outcomes early after a spinal cord injury.”
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Materials provided by eLife. Note: Content may be edited for style and length.

Observational data shows air pollution in India decreased drastically in the first COVID-19 lockdown when emissions from vehicles naturally declined, but York University researchers say those numbers only tell part of the story — blue skies and an absence of visible smog can be deceiving and hide pollutants that could potentially cause health issues.
Air pollution results from a complex mix of interactions between emissions, meteorology, such as wind direction and rain, as well as chemistry, but looking only at observational data as many recent studies have done without take meteorology into account, skews the numbers.
The researchers found that some air pollutants didn’t drop nearly as much as first thought and even more surprising was that ozone levels increased even as other pollutants decreased. The air looked much cleaner, but that allowed more sunshine to get through, creating conditions for ozone (O3) to increase up to 30 per cent.
“To accurately quantify the impact of the COVID-19 lockdown on air pollutant levels, meteorology and atmospheric chemistry needs to be considered in addition to emissions,” says York University postdoctoral researcher Leigh Crilley, who led the Faculty of Science research along with York Associate Professor Cora Young and team. “Our research shows the decline in local emissions had less influence on the decrease in air pollutants than first thought.”
As the national lockdown in India reduced major urban sources of air pollution, such as traffic, industry and construction, it gave the researchers an opportunity to study the contribution of local sources of air pollutants during normal meteorological conditions.
To get a clearer picture of potential decreases in air pollution, Crilley and Young focussed their study on nitrogen oxides (NOx), fine particulate matter (PM2.5) and O3, as well as what was happening meteorologically at multiple locations within two cities in India — Delhi and Hyderabad — during the start of the first lockdown, from March 24 to April 24, 2020.

Cold Spring Harbor Laboratory (CSHL) Associate Professor Pavel Osten and Professor Lloyd Trotman have developed a new way to study the life history of prostate cancer in mice. The pair combined their expertise in whole-organ imaging and prostate cancer to track how prostate cancer cells grow into tumors and spread to other organs. Their method allows scientists to study the behavior and properties of prostate cancer, for the first time, in a setting that accurately mimics the disease in real life. The study led by Julian Taranda, a former postdoc in the Osten lab, was published in Cell Reports.
Natural tumors usually originate from a single cell that went awry. However, synthetic tumors grown in lab mice often originate from millions of cells instead of individual ones. Trotman says this process does not accurately reflect how cancer usually starts. He explains:
“If you think of skin cancer, right? It’s going to be a cell that has suffered UV irradiation that’s going to be the trigger, not essentially your entire skin in general.”
The new approach described by Osten and Trotman uses a more tailored technique to studying very early prostate cancer. lt uses a virus to transform as little as one normal mouse prostate cell into a cancerous cell. This lone cancer cell can be located using a microscope technique called whole-organ serial two-photon tomography. The tomography machine is fully automated. It takes an image of all the cells on the top layer of an organ, slices off that piece, images what is in the next layer, and repeats the process until it has photographed the entire organ. Then, using an artificial intelligence program, the machine creates a 3D reconstruction of the organ, at single-cell resolution. Osten says this is important because:
“In the later stages of cancer, you have a big bulk of cancer cells and it’s easy to find them. In the early stage, you may have very few cells in the organ. And so looking with traditional methods is really painful because you have to slice and look and find.”
The researchers were able to track the progression of prostate cancer cells from their birth up to 20 days later, when they started spreading within the organ. Later, these fugitive cells started migrating to the liver and, unexpectedly, the brain.
The scientists hope this versatile new method will help tackle unexplored questions about the early steps of cancer’s growth and escape into other organs, wherever it starts.
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Materials provided by Cold Spring Harbor Laboratory. Original written by Luis Sandoval. Note: Content may be edited for style and length.

Idiopathic pulmonary fibrosis (IPF) is a deadly and rapidly progressing disease with no cure.
The disease involves abnormal interactions between lung cells, including fibroblasts, and their surrounding environment. Because of this, standard 2D cell culture models used for drug screening tend to perform poorly when predicting response to potential therapies.
Amid the COVID-19 pandemic and rising air pollution levels, incidence of IPF is anticipated to rise, urgently increasing the need for strong model systems.
In APL Bioengineering, from AIP Publishing, researchers from the University of Minnesota-Twin Cities and Mayo Clinic in Rochester, Minnesota, describe a 3D cell culturing platform that allows study of lung fibroblasts and their microenvironment. The platform enables measurement of cell behaviors and microenvironment changes involved in the disease progression of IPF, and the platform’s size and simplicity make it suitable for use in high-throughput drug screening protocols.
“IPF is a horrible disease that drastically impacts a patient’s life and eventually causes them to die from lack of oxygen,” said co-author Katherine Cummins. “It’s really important to have lab tools and models that create and control the microenvironment in which the cells sit, because this may be key to preclinical identification of possible treatments.”
Unlike rodent IPF models that do not mimic progressive disease and other cell culture systems that lack the surrounding microenvironment, their microtissue platform allows study of fibroblasts within an extracellular matrix (ECM). Changes in the ECM are a hallmark of IPF, so the system allows more relevant functional outputs. Moreover, its simplicity and tunability make it easy to use.
“Many organoid and lab-on-a-chip platforms can be hard to use,” said co-author David Wood. “What’s exciting is that this system is very easy to use. We’ve already disseminated it to two other labs who are using it completely independent of us.”
Validation of the system’s functioning focused primarily on ECM remodeling (i.e., cell-driven changes to the microenvironment) and cell contractility, which increases in activated, diseased fibroblasts.
Multiple tests for each of these two functions demonstrated the system robustly quantifies key aspects of fibrosis. These results were reproduced using patient-donated cells as well, indicating the system could be used for personalized medicine.
Moreover, the system’s versatility allows it to be used with different cell types and other matrix components, so it could be adapted for use in the study of other diseases where cell-microenvironment interactions contribute to disease. The research team has already used the system to study liver toxicity and anticipates it could be used across multiple solid organ systems, including in the study of cancer progression and metastasis.
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Materials provided by American Institute of Physics. Note: Content may be edited for style and length.

Researchers from Nanyang Technological University, Singapore (NTU Singapore), have modelled that pollutant emissions from the shipping sector increased significantly in major international seaports during the COVID-19 pandemic.
The findings serve as a stark contrast against findings[1] from the NASA Earth Observatory that the freeze in industrial processes and human activity arising from the pandemic resulted in generally lower air pollution.
In Singapore, the NTU research team found that emissions were modelled to have more than doubled (123 per cent), during the pandemic period, while they increased twofold in Los Angeles (100 per cent), almost two-thirds (65 per cent) in Long Beach, California, and over a quarter (27 per cent) in Hamburg, Germany.
Container ships and dry bulk carriers marked the sharpest increase of all total emissions, seeing an average increment of 94 per cent and 142 per cent respectively, compared to before the COVID-19 pandemic.
The NTU research builds upon previous studies that signalled that COVID-19 had a substantial impact on the shipping industry. The United Nations Conference on Trade and Development[2] found that COVID-19-related constraints on ships and crew in many ports led to workforce shortages and operational challenges and affected productivity, while global shipping intelligence provider S&P Global Platts[3] remarked that the unprecedented and volatile surge in cargo demand following the first wave of the COVID-19 caused further delays at almost every seaport worldwide.
The NTU study modelled that ship emissions in all four ports increased by an average of 79 per cent because of the prolonged turnaround time in port, said the researchers, with extended ‘hotelling’ time[4] at berth and anchorage areas as longer operational times were needed due to pandemic-related delays.

Since 2016, progress in reducing malaria-related incidence and deaths over the past decade has been slowing down. On top of this, restrictions put in place to contain the COVID-19 pandemic have further limited malaria control programs such as mass bed net distribution and indoor residual spraying campaigns. To regain the momentum toward malaria elimination, scientists have increasingly turned to malaria parasite genomics to get a better understanding of the epidemiology and transmission dynamics, and the genetic basis underlying drug resistance and disease severity.
“A comprehensive picture of a population of parasites requires an understanding of them on the individual genome level,” says Professor Akira Kaneko of the Department of Parasitology, Osaka City University Graduate School of Medicine.
For the past decade, Professor Kaneko and his collaborators have conducted various studies on malaria in and around Lake Victoria, Kenya, where the disease burden is among the highest in the country, to find ways to eliminate malaria successfully. To gain more insights into the genomic diversity and population dynamics of Plasmodium falciparum, the deadliest malaria parasite in humans, Kaneko and his collaborators generated whole genome sequence data from 48 parasite isolates and compared them with parasites from other parts of Africa. They described their findings in the journal Scientific Reports.
Analyses based on single nucleotide polymorphisms (SNPs) or point mutations showed that P. falciparum parasites from Lake Victoria formed a distinct subpopulation within the larger East African parasite population, caused in part by the greater contribution of Central African parasites to the ancestral genomes of Lake Victoria parasites. Moreover, the team identified a number of SNPs that can potentially be used in a molecular surveillance tool to determine the main routes of transmission and migration of P. falciparum. “The population-specific SNPs we identified provide a high degree of small-scale specificity, typically to the country of origin, “states Professor Kaneko. “Combine these with the wider regional or continental view gained from population-specific organellar SNPs, and we could have the degree of resolution needed to generate an effective molecular surveillance tool.”
Another important piece to the picture were the drug resistance markers that the team observed circulating among P. falciparum isolates around Lake Victoria. They saw the persistence of the main resistance marker for the drug chloroquine, as well as high frequencies of mutations associated with sulfadoxine-pyrimethamine (SP) resistance. The team believed that the continued use of SP as intermittent preventative treatment by pregnant women (IPTp) is likely providing enough selective pressure to maintain these polymorphisms in P. falciparum.
“We are especially excited about the potential application of the data we found regarding variations of P. falciparum and known drug resistance biomarkers we observed in parasite isolates from the area,” says Dr. Wataru Kagaya, Medical Lecturer of the Department of Parasitology, Osaka City University Graduate School of Medicine. One in particular stood out. They confirmed the presence of the S160N/T mutation in the gene Pfap2mu, which was first documented in Kenyan children with delayed parasite clearance when treated with artemisinin-based combination therapies (ACTs), currently the first-line treatment for uncomplicated malaria. “Our work is expected to assist in the clinical management and disease control through surveillance activities in regions with high malaria burden,” adds Kagaya.
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Materials provided by Osaka City University. Note: Content may be edited for style and length.

The creation of nanoscale computers for use in precision health care has long been a dream of many scientists and health care providers. Now, for the first time, researchers at Penn State have produced a nanocomputing agent that can control the function of a particular protein that is involved in cell movement and cancer metastasis. The research paves the way for the construction of complex nanoscale computers for the prevention and treatment of cancer and other diseases.
Nikolay Dokholyan, G. Thomas Passananti Professor, Penn State College of Medicine, and his colleagues — including Yashavantha Vishweshwaraiah, postdoctoral scholar in pharmacology, Penn State — created a transistor-like ‘logic gate,’ which is a type of computational operation in which multiple inputs control an output.
“Our logic gate is just the beginning of what you could call cellular computing,” he said, “but it is a major milestone because it demonstrates the ability to embed conditional operations in a protein and control its function, said Dokholyan. “It will allow us to gain a deeper understanding of human biology and disease and introduces possibilities for the development of precision therapeutics.”
The team’s logic gate comprised two sensor domains designed to respond to two inputs — light and the drug rapamycin. The team targeted the protein focal adhesion kinase (FAK) because it is involved in cell adhesion and movement, which are initial steps in the development of metastatic cancer.
“First, we introduced a rapamycin-sensitive domain, called uniRapr, which the lab had previously designed and studied, into the gene that encodes FAK,” said Vishweshwaraiah. “Next, we introduced the domain, LOV2, which is sensitive to light. Once we optimized both domains, we combined them into one final logic-gate design.”
The team inserted the modified gene into HeLa cancer cells and, using confocal microscopy, observed the cells in vitro. They studied the effects of each of the inputs separately, as well as the combined effects of the inputs, on the cells’ behavior.
They discovered that not only could they rapidly activate FAK using light and rapamycin, but also that this activation resulted in the cells undergoing internal changes that enhanced their adhesive capabilities, which ultimately decreased their motility.
Their results published today (Nov. 16) in the journal Nature Communications.
“We show for the first time that we can build a functioning nanocomputing agent within living cells that can control cell behavior,” said Vishweshwaraiah. “We also discovered some interesting features of the FAK protein, such as the changes it triggers in cells when it is activated.”
Dokholyan noted that the team hopes to eventually test these nanocomputing agents in vivo within living organisms.
Other Penn State authors on the paper include Jiaxing Chen, graduate student; Venkat R. Chirasani, postdoctoral fellow; and Erdem D. Tabdanov, assistant professor of pharmacology.
The National Institutes of Health and the Passan Foundation supported this research.
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Materials provided by Penn State. Original written by Sara LaJeunesse. Note: Content may be edited for style and length.

A study comparing the impact of diet versus drugs on the inner workings of our cells has found nutrition has a much stronger impact.
The pre-clinical study by the University of Sydney’s Charles Perkins Centre suggests the makeup of our diet could be more powerful than drugs in keeping conditions like diabetes, stroke and heart disease at bay.
Conducted in mice, the research showed nutrition (including overall calories and macronutrient balance) had a greater impact on ageing and metabolic health than three drugs commonly used to treat diabetes and slow down ageing.
The findings are published in Cell Metabolism.
The research builds on the team’s pioneering work in mice and humans demonstrating the protective role of diet and specific combinations of proteins, fats and carbohydrates against ageing, obesity, heart disease, immune dysfunction and risk of metabolic diseases, such as type 2 diabetes.
Senior author and Academic Director of the Charles Perkins Centre, Professor Stephen Simpson said drugs can also target the same biochemical pathways as nutrients. There has been a huge effort to discover drugs aimed at improving metabolic health and ageing without requiring a change in diet, he said.

When the pro-inflammatory pair, a receptor called CCR2 and its ligand CCL-2, get together, it increases the risk of developing type 1 diabetes, scientists report.
In this autoimmune disease that typically surfaces in childhood, the interaction of this natural lock and key recruits immune cells to the pancreas, which attack the insulin-producing islet cells, resulting in a lifelong course of insulin therapy and a lifelong increased risk of other health problems like heart and kidney disease, says Dr. Sharad Purohit, biochemist in the Center for Biotechnology and Genomic Medicine at the Medical College of Georgia.
The study, published in the Journal of Translational Autoimmunity, provides evidence the CCR2 gene promotes progression to type 1 as it provides new insight on how to delay disease progression, says Paul Tran, MD/PhD student at MCG at Augusta University. Tran and Purohit are the study’s first authors.
The scientists were able to put the pieces together by looking at the longitudinal data on 310 people enrolled in DAISY, a National Institutes of Health-funded study based at the University of Colorado Anschutz Medical Campus in Aurora, that has been following individuals considered at risk for type 1 because of having a relative with it or having one of the genes associated with it since 1993.
The new study focused on 42 individuals who persistently had antibodies against the insulin-producing islet cells but never actually developed type 1, 48 who did develop type 1 and the remainder who did neither and served as the control group.
They found that blood levels of CCL-2, the ligand for CCR2, were lower in both individuals who had antibodies but not actual disease as well as those who progressed to type 1 diabetes, Tran says.