Blue-eyed humans have a single, common ancestor

 New research shows that people with blue eyes have a single, common ancestor. A team at the University of Copenhagen have tracked down a genetic mutation which took place 6-10,000 years ago and is the cause of the eye colour of all blue-eyed humans alive on the planet today.

What is the genetic mutation

"Originally, we all had brown eyes," said Professor Hans Eiberg from the Department of Cellular and Molecular Medicine. "But a genetic mutation affecting the OCA2 gene in our chromosomes resulted in the creation of a "switch," which literally "turned off" the ability to produce brown eyes." The OCA2 gene codes for the so-called P protein, which is involved in the production of melanin, the pigment that gives colour to our hair, eyes and skin. The "switch," which is located in the gene adjacent to OCA2 does not, however, turn off the gene entirely, but rather limits its action to reducing the production of melanin in the iris -- effectively "diluting" brown eyes to blue. The switch's effect on OCA2 is very specific therefore. If the OCA2 gene had been completely destroyed or turned off, human beings would be without melanin in their hair, eyes or skin colour -- a condition known as albinism.

Limited genetic variation

Variation in the colour of the eyes from brown to green can all be explained by the amount of melanin in the iris, but blue-eyed individuals only have a small degree of variation in the amount of melanin in their eyes. "From this we can conclude that all blue-eyed individuals are linked to the same ancestor," says Professor Eiberg. "They have all inherited the same switch at exactly the same spot in their DNA." Brown-eyed individuals, by contrast, have considerable individual variation in the area of their DNA that controls melanin production.

Professor Eiberg and his team examined mitochondrial DNA and compared the eye colour of blue-eyed individuals in countries as diverse as Jordan, Denmark and Turkey. His findings are the latest in a decade of genetic research, which began in 1996, when Professor Eiberg first implicated the OCA2 gene as being responsible for eye colour.

Nature shuffles our genes

The mutation of brown eyes to blue represents neither a positive nor a negative mutation. It is one of several mutations such as hair colour, baldness, freckles and beauty spots, which neither increases nor reduces a human's chance of survival. As Professor Eiberg says, "it simply shows that nature is constantly shuffling the human genome, creating a genetic cocktail of human chromosomes and trying out different changes as it does so."

Source: Sciencedaily

How meditation can help you make fewer mistakes

 If you are forgetful or make mistakes when in a hurry, a new study from Michigan State University -- the largest of its kind to-date -- found that meditation could help you to become less error prone.

The research, published in Brain Sciences, tested how open monitoring meditation -- or, meditation that focuses awareness on feelings, thoughts or sensations as they unfold in one's mind and body -- altered brain activity in a way that suggests increased error recognition.

"People's interest in meditation and mindfulness is outpacing what science can prove in terms of effects and benefits," said Jeff Lin, MSU psychology doctoral candidate and study co-author. "But it's amazing to me that we were able to see how one session of a guided meditation can produce changes to brain activity in non-meditators."

The findings suggest that different forms of meditation can have different neurocognitive effects and Lin explained that there is little research about how open monitoring meditation impacts error recognition.

"Some forms of meditation have you focus on a single object, commonly your breath, but open monitoring meditation is a bit different," Lin said. "It has you tune inward and pay attention to everything going on in your mind and body. The goal is to sit quietly and pay close attention to where the mind travels without getting too caught up in the scenery."

Lin and his MSU co-authors -- William Eckerle, Ling Peng and Jason Moser -- recruited more than 200 participants to test how open monitoring meditation affected how people detect and respond to errors.

The participants, who had never meditated before, were taken through a 20-minute open monitoring meditation exercise while the researchers measured brain activity through electroencephalography, or EEG. Then, they completed a computerized distraction test.

"The EEG can measure brain activity at the millisecond level, so we got precise measures of neural activity right after mistakes compared to correct responses," Lin said. "A certain neural signal occurs about half a second after an error called the error positivity, which is linked to conscious error recognition. We found that the strength of this signal is increased in the meditators relative to controls."

While the meditators didn't have immediate improvements to actual task performance, the researchers' findings offer a promising window into the potential of sustained meditation.

"These findings are a strong demonstration of what just 20 minutes of meditation can do to enhance the brain's ability to detect and pay attention to mistakes," Moser said. "It makes us feel more confident in what mindfulness meditation might really be capable of for performance and daily functioning right there in the moment."

While meditation and mindfulness have gained mainstream interest in recent years, Lin is among a relatively small group of researchers that take a neuroscientific approach to assessing their psychological and performance effects.

Looking ahead, Lin said that the next phase of research will be to include a broader group of participants, test different forms of meditation and determine whether changes in brain activity can translate to behavioral changes with more long-term practice.

"It's great to see the public's enthusiasm for mindfulness, but there's still plenty of work from a scientific perspective to be done to understand the benefits it can have, and equally importantly, how it actually works," Lin said. "It's time we start looking at it through a more rigorous lens."

Source: Sciencedaily

Cells dancing harmonic duets could enable personalized cancer therapies

 Mechanical engineers at Duke University are using two electronic "voices" singing a harmonic duet to control suspended particles and cells in new and valuable ways. Their prototype device can form and rotate a single-layer crystal from a group of particles, create arbitrary shapes with a given number of particles, and move pairs of biological cells together and apart again hundreds of times.

These abilities could serve a wide variety of fields, such as materials science, soft condensed-matter physics, biophysics, life science and medicine.

For example, the researchers have shown that the device can selectively pair two individual cells and measure their adhesion forces -- a feat that doctors could use to determine treatment for individual cancer patients. Because of the dexterity and gentleness of the acoustic device, the researchers have named it the HANDS platform. (Harmonic Acoustics for Non-contact, Dynamic, Selective particle manipulation.)

The results appear online on March 24 in the journal Nature Materials.

"The separation of paired particles or cells has been a major target in the field of acoustic manipulation for many years," said Tony Jun Huang, the William Bevan Distinguished Professor of Mechanical Engineering and Materials Science at Duke. "Our HANDS platform is the first method of separating paired objects, which provides a way into cell-cell interaction studies that are needed extensively in biophysics studies and drug discovery."

Acoustic tweezers are a rapidly developing field that uses various physical phenomena of sound waves to gently manipulate particles or cells suspended in liquids without touching them. Some examples pinch particles between two sound waves and adjust the waves' phase or origination point to move them. Others create patterns by combining two static standing sound waves together to separate particles into different formations, such as a grid.

Now, researchers have added a new layer of complexity to these devices by introducing piezoelectric melodies and harmonies into the setup. Where previous devices create static standing waves, the HANDS platform prototype uses a function generator to create complex standing waves that change rapidly. One could think of it as, rather than the machines singing a single note, they're now hitting the rapid highs and lows of a complicated opera with two singers.

The new device works by placing sound-creating transducers on each side of a small square chamber filled with liquid. These four transducers work in step with those directly across from them, forming two pairs. One creates patterns in the chamber horizontally and the other vertically. The interaction of these two complex, quickly changing sound wave patterns creates dynamic abilities never before demonstrated within the field.

"I simulated how these waves might combine to manipulate the particles in the chamber and then ran experiments to see actual results," said Shujie Yang, a postdoctoral associate in the Huang laboratory. "It took a long time and many trials, but finally the simulations became good enough to start matching the results. And once the simulations were accurate, I could begin predicting new abilities."

In the paper, Yang demonstrates several novel abilities of the harmonic duet acoustic tweezers. In one experiment, he shows that the HANDS platform can flatten and pattern a 3D cluster of 24 particles into a crystalline structure. It can spin these flat formations like a plate on a fingertip.

Moving to individual particle manipulation, the paper demonstrates particles coaxed into three different formations bearing a striking resemblance to the letters O, D and K. The device then pairs together dozens of single particles like teenagers at a school dance and shows that it can pull each pair apart and put them back together again more than a thousand times.

In the final demonstration, Yang shows that the device can select a single pair of cells out of a lineup, push them together and pull them back apart. He then uses this ability to measure the adhesion forces at work between two cells touching one another.

According to the researchers, this is the most exciting ability of the HANDS platform, as it could allow detailed tests for personalized medicine.

"I am thrilled about the capabilities of this platform, which is as gentle as a mother's hands," said Luke Lee, professor of medicine at Harvard Medical School, who is a co-leader of the research. "Gentle and sensitive mother's hands allow us to establish the foundation of quantitative cell biology and translational precision medicine."

"For example, we can systematically study T-cell interactions with cancer cells in a high-throughput manner and obtain precision cell-cell interaction forces," Lee said. "This could help doctors find the most effective and specific cell therapy for patients as personalized precision medicine."

Source: Sciencedaily

Large study challenges the theory that light alcohol consumption benefits heart health

 Observational research has suggested that light alcohol consumption may provide heart-related health benefits, but in a large study published in JAMA Network Open, alcohol intake at all levels was linked with higher risks of cardiovascular disease. The findings, which are published by a team led by researchers at Massachusetts General Hospital (MGH) and the Broad Institute of MIT and Harvard, suggest that the supposed benefits of alcohol consumption may actually be attributed to other lifestyle factors that are common among light to moderate drinkers.

The study included 371,463 adults -- with an average age of 57 years and an average alcohol consumption of 9.2 drinks per week -- who were participants in the UK Biobank, a large-scale biomedical database and research resource containing in-depth genetic and health information. Consistent with earlier studies, investigators found that light to moderate drinkers had the lowest heart disease risk, followed by people who abstained from drinking. People who drank heavily had the highest risk. However, the team also found that light to moderate drinkers tended to have healthier lifestyles than abstainers -- such as more physical activity and vegetable intake, and less smoking. Taking just a few lifestyle factors into account significantly lowered any benefit associated with alcohol consumption.

The study also applied the latest techniques in a method called Mendelian randomization, which uses genetic variants to determine whether an observed link between an exposure and an outcome is consistent with a causal effect -- in this case, whether light alcohol consumption causes a person to be protected against cardiovascular disease. "Newer and more advanced techniques in 'non-linear Mendelian randomization' now permit the use of human genetic data to evaluate the direction and magnitude of disease risk associated with different levels of an exposure," says senior author Krishna G. Aragam, MD, MS, a cardiologist at MGH and an associate scientist at the Broad Institute. "We therefore leveraged these new techniques and expansive genetic and phenotypic data from biobank populations to better understand the association between habitual alcohol intake and cardiovascular disease."

When the scientists conducted such genetic analyses of samples taken from participants, they found that individuals with genetic variants that predicted higher alcohol consumption were indeed more likely to consume greater amounts of alcohol, and more likely to have hypertension and coronary artery disease. The analyses also revealed substantial differences in cardiovascular risk across the spectrum of alcohol consumption among both men and women, with minimal increases in risk when going from zero to seven drinks per week, much higher risk increases when progressing from seven to 14 drinks per week, and especially high risk when consuming 21 or more drinks per week. Notably, the findings suggest a rise in cardiovascular risk even at levels deemed "low risk" by national guidelines from the U.S. Department of Agriculture (i.e. below two drinks per day for men and one drink per day for women).

The discovery that the relationship between alcohol intake and cardiovascular risk is not a linear one but rather an exponential one was supported by an additional analysis of data on 30,716 participants in the Mass General Brigham Biobank. Therefore, while cutting back on consumption can benefit even people who drink one alcoholic beverage per day, the health gains of cutting back may be more substantial -- and, perhaps, more clinically meaningful -- in those who consume more.

"The findings affirm that alcohol intake should not be recommended to improve cardiovascular health; rather, that reducing alcohol intake will likely reduce cardiovascular risk in all individuals, albeit to different extents based on one's current level of consumption," says Aragam.

The study's lead author was Kiran J. Biddinger, and additional authors included Connor A. Emdin, MD, DPhil, Mary E. Haas, PhD, Minxian Wang, PhD, George Hindy, MD, Patrick T. Ellinor, MD, PhD, Sekar Kathiresan, MD, and Amit V. Khera, MD, MSc.

Funding was provided by the National Institutes of Health and the American Heart Association.

Source: Sciencedaily

Once called cellular debris, tiny bubbles may play key role in understanding, treating diseases

 Scientists have long puzzled about a critical way that cells communicate with one another, but Rutgers researchers have used a simple roundworm to solve the mystery.

The study, which appears in the journal Current Biology, could help to develop treatments for Alzheimer's and other neurodegenerative diseases.

Cells share good news and bad news with each other, and one way in which they do that is through tiny bubbles called extracellular vesicles (EVs). Once considered to be cellular debris, EVs carry beneficial or toxic cargo that promotes good health or disease. In the human brain, for example, EVs carry disease-causing proteins that may influence the progression of Alzheimer's disease.

"Although EVs are of profound medical importance, the field lacks a basic understanding of how EVs form, what cargo is packaged in different types of EVs originating from same or different cell types and how different cargos influence the range of EV targeting and bioactivities," said lead author Inna Nikonorova, a postdoctoral researcher.

EVs, which are found in human fluids including urine and blood, may be used in liquid biopsies as biomarkers for disease because healthy and sick cells package different EV cargo.

The Rutgers' research team decided to use a simple experimental animal -- C. elegans, or roundworms -- and cutting edge genetic, molecular, biochemical and computational tools to study the unknown function that EVs have within our bodies.

Maureen Barr, a professor in the Department of Genetics, and Nikonorova developed a large-scale identification project that identified 2,888 EV cargo candidates.

Given the importance of EVs in the human nervous system, Nikonorova focused on EVs produced by cilia, the cellular antennae that transmit and receive signals for intercellular communication. Specifically, the researchers focused on EV cargo produced by nerve cells and discovered that EVs carry RNA-binding proteins as well as RNA, whose role in effective therapies is seen in the COVID-19 mRNA vaccine.

Nikonorova and Barr hypothesized that neurons package RNA-binding proteins and RNA into EVs to drive communication between cells and between animals. A fundamental understanding of EV-RNA biology is important for developing tailor-made EVs for RNA-based therapies.

"We developed an innovative method to label, track and profile EVs using genetically encoded, fluorescent-tagged EV cargo and conducted a large-scale isolation and protein profiling," Nikonorova said. "Using this strategy, we discovered four novel cilia EV cargo. Combined, these data indicate that C. elegans produces a complex and heterogeneous mixture of EVs from multiple tissues in living animals and suggests that these environmental EVs play diverse roles in animal physiology."

Future efforts in the Barr laboratory will be directed toward understanding EV-mediated RNA communication. Research in the Barr laboratory is funded by the National Institute of Neurological Disorders and Stroke and the National Institute of Diabetes and Digestive and Kidney Diseases.

Source: Sciencedaily

COPD in numbers: How many people have it, who's more at risk?

 

• Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of death worldwide.
• Researchers from the University of Edinburgh found that almost 4 in 5 cases of COPD occur in low and middle-income countries (LMICs), mainly the Western Pacific Region.
• The research team also found that males are twice as likely to develop COPD as females.
• The scientists hope their research will place increased awareness on the global burden of COPD.

Chronic Obstructive Pulmonary Disease (COPD) is a medical term used to describe a set of respiratory diseases, including chronic bronchitis and emphysema. COPD is the third leading cause of deathTrusted Source worldwide.

“COPD is a leading cause of disease burden globally, receiving little to no attention in many LMICs,” Dr. Davies Adeloye, Ph.D., research fellow in global health at Usher Institute at the University of Edinburgh in the United Kingdom told Medical News Today.

Dr. Adeloye is a co-first author of a new systematic review and modeling study examining the global prevalence of and risk factors for COPD to help guide policy and population interventions.

“This study is the first, to our knowledge, to report the prevalence and number of cases of COPD based on the two widely used case definitions at global, regional, and national levels,” said Dr. Adeloye.

The results from this study appear in the journal The LancetTrusted Source.

Analyzing global COPD prevalence

For this study, the research team used data from 162 COPD-related population-based studies conducted between January 1990 and December 2019. The studies represented 260 sites in 65 countries.

When gathering data for the study, researchers accounted for several factors. For example, they used data from two different COPD definitions based on spirometry testing, which measures airflow into and out of the lungs.

One definition, as per the Global Initiative on Obstructive Lung Disease (GOLD), recommends using spirometry testing as the “gold standard” for measuring lung function. The second definition, called the lower limit of normal (LLN)Trusted Source definition, also takes into consideration a person’s age during diagnosis.

Researchers classified this data into 10 different regions. These regions included high-income countries (HICs) such as the Americas, European, Eastern Mediterranean, and the Western Pacific regions. They also included LMICs in Africa, Southeast Asia, and specific regions of the Americas, Europe, Western Pacific, and Eastern Mediterranean region.

Dr. Adeloye and his research team also included global risk factors for COPD in their model:

• sex, age, and body mass index (BMI)
• smoking
• exposure to smoking, biomass, and/or dust
• past medical and family history, including history of tuberculosis
• socioeconomic status
• education
• place of residence

Risk factors for COPD

Under the GOLD definition of COPD, researchers found COPD affected about 10.3% of the world’s population aged 30–79 years — almost 392 million people — in 2019. Under the LLN definition, the percentage for the same population dropped to 7.6%, or about 292 million people.

Only using the GOLD definition, the research team determined that most of the 392 million people living with COPD in 2019 — about 315.5 million or 4 in 5 cases — lived in LMICs.

“We believe this is largely a reflection of the higher prevalence of main risk factors for COPD in many LMICs, such as tobacco smoking, exposure to biomass smoke, and air pollution,” Dr. Adeloye explained.

The highest percentage, about 11.7%, of those with GOLD-defined COPD were located in the Western Pacific region.

“We believe this is so due to the combined effects of smoking and nonsmoking risks — particularly underweight and biomass exposure — in many settings in these regions,” Dr. Adeloye detailed.

“The large populations in these settings have also resulted in larger overall cases,” he added.

As for risk factors, under the GOLD definition, Dr. Adeloye and his research team found males aged 30–79 were twice as likely as females to have COPD.

Source: Medical News Today

Less than half of transgender people feel supported by family doctor

 

• A new study that took place in New Zealand has shown that, for transgender individuals, negative experiences with healthcare professionals are associated with an increased risk of psychological distress and suicidal thoughts.
• In contrast, positive or supportive experiences with primary care physicians (PCPs) reduced the risk of these negative mental health outcomes.
• This study highlights the importance of improving the awareness and education of PCPs about transgender healthcare.

Studies have consistently shown that transgender individuals have a higher risk of mental health issues than cisgender individuals.

A new study found that transgender individuals who reported supportive experiences with their PCP were less likely to experience symptoms of anxiety or depression or have suicidal thoughts.

However, only about half of the surveyed individuals reported a positive experience with their PCP, highlighting the importance of training healthcare professionals to improve the care of transgender individuals.

The study appears in the journal Family Practice.

Interactions with healthcare professionals

Negative interactions with healthcare professionals are prevalent among transgender individuals. A lack of awareness and educationTrusted Source among medical staff about the healthcare needs of transgender individuals are some of the reasons for these negative healthcare experiences.

However, even small steps indicative of respect toward transgender individuals, such as the use of correct gender pronouns and current names, can contribute to a positive healthcare experience.

Previous studies have shown that the frequent negative healthcare experiences of transgender individuals are associated with a higher risk of depression and suicidal thoughts.

However, the current study is the first to assess the effects of positive or supportive healthcare experiences on mental health outcomes in transgender individuals in New Zealand.

Counting Ourselves survey 

The researchers used data from the 2018 Counting Ourselves survey, which collects information on the health of transgender individuals aged 14 years or older residing in New Zealand.

The study included 948 transgender individuals who provided feedback on their negative and positive healthcare experiences and mental health.

The scientists used a standardized questionnaire to assess psychological distress levels on the basis of the anxiety and depressive symptoms that the individuals had experienced in the previous 4 weeks.

The researchers also determined the number of self-harm attempts and the frequency of suicidal thoughts or behaviors in the previous 12 months.

Source: Medical News Today

Do anti-inflammatory diets really work?

An anti-inflammatory diet is richTrusted Source in foods containing health-promoting antioxidants, polyphenols, and other immune-boosting compounds that have the potential to fight inflammation in the body.

Inflammation is the body’s natural response to injury and infection. However, experts link persistent and chronic inflammationTrusted Source to insulin resistance and an increased risk of diabetes, heart disease, cancer, Alzheimer’s disease, and many other chronic conditions.

Foods with anti-inflammatory properties include, but are not limited to:

• herbs and spicesTrusted Source, such as turmeric, cinnamon, ginger, garlic, pepper, and rosemary
• fruit, including pineapple, papaya, mango, berries, and acerola cherry
• vegetables, such as carrots, pumpkin, green leafy vegetables, and zucchini
• peas and beans, such as pinto beans, chickpeas, lentils, and black-eyed peas
• oily fish and other omega-3 sources, including sardines, salmon, mackerel, herring, and fish oil
• dairy, such as yogurt
• whole grains, such as corn, cornmeal, and whole grain pasta, bread, and rice

How does an anti-inflammatory diet work?

According to researchTrusted Source, several foods cause inflammation in the body, including highly refined carbohydrates and added sugars, red meat, trans and saturated fats, and saltTrusted Source.

Although there is no well-defined anti-inflammatory diet, there are broad recommendations for foods to get more of and those to get less of to treat inflammation in the body.

Furthermore, studies show that diets not designed as anti-inflammatory have inflammation-lowering benefits, and health experts recommend them for general good health.

For instance, the Mediterranean dietTrusted Source and the dietary approaches to stop hypertensionTrusted Source diet — designed to reduce the risk of heart disease and blood pressure, respectively — are effective anti-inflammatory diets.

The goal of an anti-inflammatory diet is to eliminate pro-inflammatory foods and replace them with nutritionally adequate foods and herbs and spices that are high in anti-inflammation compounds, such as vitamin CTrusted Source.

For instance, avoiding refined flour, excess salt from precooked foods, and sugary beverages and increasing one’s daily intake of fruit, vegetables, and whole grains are among common recommendations.

Anti-inflammatory diets also support gut health. As many as 70–80%Trusted Source of immune cells are present in the gut, so optimizing gut health is integral to promoting immune health and eliminating chronic inflammation.

It is advisable to consume foods rich in prebiotics and probiotics, such as legumes and yogurt, every day.

Tips for getting started on an anti-inflammatory diet include the following:

• Replace sugar-sweetened beverages, such as sodas and concentrated juices, with plain or fruit-infused water.
• Increase your fiber intake by eating more whole grains, fruits, and vegetables daily.
• Eat fatty fish, including sardines and salmon, twice per week.
• Include into your diet more nuts, seeds, nut butter, avocado, and olive oil for healthy fats.
• Incorporate more herbs and spices.
• Sip on herbal teas, such as ginger, garlic, cinnamon, or rosemary tea.

Potential health benefits

Lower disease risk

According to the Centers for Disease Control and Prevention (CDC)Trusted Source, chronic conditions, such as heart disease and stroke, are the leading cause of death and disability in the United States.

ResearchTrusted Source demonstrates that anti-inflammatory diets reduce markers of inflammation in the body and the risk of chronic conditions.

A 2016 reviewTrusted Source found that the Mediterranean diet reduced C-reactive protein — a test that indicates inflammation in the body — by 20%, and overall heart disease risk by 30%.

Researchers suggest that the diet reduces heart disease risk by lowering inflammation in blood vessel walls and maintaining their health and resilience.

Adherence to the Mediterranean diet also has the potential to reduce the risk of developingTrusted Source rheumatoid arthritis, although more studies are necessary to explore this benefit.

Less severe symptoms

Symptoms of chronic conditions, such as muscle pain, swollen joints, itchy skin, tiredness, and mood swings, may become debilitating or disruptive, affecting a person’s quality of life and comfort.

Research into the effects of an anti-inflammatory diet in individuals with psoriasisTrusted Source, chronic obstructive pulmonary diseaseTrusted Source, and depressionTrusted Source found improvement of some symptoms and quality of life in some instances.

This means that for someone with a chronic condition, an anti-inflammatory diet may support improved symptom management and a better quality of life.

In addition, other researchTrusted Source notes that anti-inflammatory diets may reduce fatigue brought on by a chronic condition.

However, instead of focusing on a single nutrient, people should follow a balanced diet rich in fiber, whole grains, fruit, vegetables, and omega-3 fats to manage fatigue.

Source: Medical News Today

New therapy may stop metastasis in triple-negative breast cancer

 

• Scientists have shown that the expression of the oncoprotein MYC is altered in the majority of cancers.
• Scientists have also demonstrated that inhibiting MYC can reduce tumor progression.
• However, some scientists have concerns that inhibiting MYC may inadvertently promote the spread of cancer.
• In the present study, researchers found that the MYC inhibitor Omomyc stopped the spread of triple-negative breast cancer in mice.

The study, which appears in the journal Cancer Research Communications, offers hope that Omomyc may also be effective in humans.

MYC

The oncoprotein MYC plays a role in promoting most human forms of cancer. Oncoproteins are produced by genes that promote cancer. Scientists have found that MYC encourages the proliferation of cancer cells and increases their survival.

While MYC’s role in the development of tumors is clear, scientists are split on whether MYC promotes metastasis — the spread of tumors to other parts of a person’s body.

Some scientists suggest MYC encourages this spread, while others indicate it inhibits the spread of tumors.

Consequently, the scientists behind the present study wanted to get more information to help resolve this debate.

Medical News Today spoke to Dr. Laura Soucek of the Vall D’hebron Institute of Oncology, Barcelona, Spain, and the study’s corresponding author.

“My laboratory has been focusing on MYC, a ‘most wanted’ target in cancer therapy, since its inception,” said Dr. Soucek.

“With this latest work, we aimed at shedding light on a controversial subject in MYC biology. In fact, while MYC had a well-established role in primary tumor progression, its role in metastasis was still not clear, since there were contrasting reports in the literature suggesting both a pro-metastatic and antimetastatic function for it, so that caution was recommended when using an MYC inhibitor in a metastatic setting.”

“Essentially, they were telling us that inhibiting MYC could well help in treating primary tumors but at the same time could promote new metastases. Since novel MYC inhibitors are finally reaching the clinic and are being tested in advanced metastatic patients, it was a priority for us and for the entire MYC biology field to clarify this risk.”

Pre-clinical study

Dr. Soucek and her colleagues have developed the MYC inhibitor Omomyc, and in previous research have shown its effects on inhibiting tumor growth.

In the present study, the researchers were particularly interested in the effects Omomyc might have on metastasis in triple-negative breast cancerTrusted Source, an aggressive form of cancer that is difficult for clinicians to treat.

“We focused on triple-negative breast cancer, the most aggressive subtype of breast cancer, which often presents metastasis already at diagnosis. Nowadays, metastases are the real challenge in cancer treatment because of their frequent resistance to therapy,” explained Dr. Soucek.

Promising results

After examining the effects of Omomyc on in vitro cells and then in mice, Dr. Soucek and her colleagues found promising results.

“Our data in pre-clinical models — cells and animal models — show that MYC inhibition by Omomyc has a profound effect on different aspects of the metastatic process, both preventing establishment of the metastatic lesions and reducing them in number and volume once they are already formed,” said Dr. Soucek.

“In some cases, metastases were even eradicated,” says Dr. Daniel Massó-Vallés, a previous postdoctoral researcher at the cancer research company Peptomyc and the first author of the study.

Dr. Pavani Chalasani — of the College of Medicine Tucson, University of Arizona — spoke to MNT, praising the study. Dr. Chalasani was not involved in the research.

“The authors present very interesting, novel, and exciting results on MYC inhibition as a potential treatment option,” noted Dr. Chalasani.

Dr. Soucek said that plans were already afoot to test whether Omomyc also inhibited tumor development and metastasis in humans.

Source: Medical News Today

Why the AstraZeneca vaccine is linked with rare blood clots: New insights

 

• Healthcare professionals have administered over 11 billion COVID-19 vaccine doses globally so far.
• However, there have been reports of a low risk of blood clotting complications linked to adenovirus-based COVID-19 vaccines.
• A recent study offers a possible explanation as to why this happens in some people.
• The research found that the electrical charge of the adenovirus promotes the adhesion of blood-based proteins associated with blood clotting.

Vaccines provide excellent immunity against severe SARS-CoV-2 infection, the virus responsible for the COVID-19 pandemic. Studies have shown that vaccines can reduceTrusted Source hospitalization and death risk by over 99% and up to 71.6% against infection with the Omicron variant.

There are three main types of COVID-19 vaccines that are currently widely used:

• mRNA vaccines: These use laboratory-made messenger RNA to teach the body’s immune cells to make a protein that triggers the body’s immune response.
• Viral vector vaccines: These vaccines use a harmless virus called the ‘vector virus,’ which is modified to deliver instructions to the immune cells to trigger them to produce antibodies to fight the infection.
• Inactivated virus vaccines: These contain a dead version of a virus that cannot replicate but can trigger the body’s immune system to create antibodies to protect against the live virus if it were to invade.

The two main viral vector vaccines in use are ChAdOx1, developed by Oxford University-AstraZeneca, and Ad26.COV2.S, developed by Johnson & Johnson (J&J). Both vaccines use adenovirusesTrusted Source as vector viruses to mount an immune response against SARS-CoV-2.

Despite their success, adenovirus-based vaccines have been linked to a small numberTrusted Source of people who have experienced thrombosis with thrombocytopenia (TTS), a potentially life threatening blood clotting disorder.

A recent study carried out by scientists at Arizona State University and the Mayo Clinic, published in the journal Science Advances, shed light on the possible mechanisms. The authors also detailed the interaction between the AstraZeneca vaccine and protein stored inside the blood’s platelets called platelet factor (PF4)Trusted Source. PF4 is released when platelets are activated.

The risk of blood-clotting complications

The blood-clotting disorder TTS is a very rare condition.

A recent review by the Global Advisory Committee on Vaccine Safety (GACVS)Trusted Source for the World Health Organization (WHO) reported that 1 in 250,000 adults in the United Kingdom and approximately 1 per 100,000 vaccinated adults in the European Union (EU) developed TTS.

According to one dataset, approximately 63.8% of the world’s population has had 1 dose of a COVID-19 vaccine, amounting to over 11.04 billion doses globally. Studies and real-world data have shown that the risk of death with or due to COVID-19 is 93.4% lower in vaccinated people (3 doses).

Despite the low incidence of TTS, mass vaccination has resulted in some people developing the condition. Scientists do not understand the exact mechanism behind TTS.

However, they think that vaccination with an adenovirus causes platelet factor 4 (PF4)Trusted Source, a protein in the blood, to bind to the adenovirus, forming a complex. Platelets are the tiny blood cells that help the body form clots to stop bleeding. Some people form antibodiesTrusted Source against this antigen-PF4 complex, which causes the platelets to aggregate, leading to an increased risk of blood clots.

Computer models and laboratory tests

To investigate blood clots associated with the Oxford-AstraZeneca COVID-19 vaccine, researchers used state-of-the-art computer modeling to understand how the adenovirus-based jab interacted with the proteins of the human body.

The team began by defining the structure of the AstraZeneca viral vector before using Atomic Resolution Brownian Dynamics (ARBD) computational modeling to demonstrate the electrostatic interaction between the vaccine particle and PF4.

The team found PF4 formed stable complexes with the adenoviruses. They discovered that the negative charge of the vaccine particle attracted the positive charge of the PF4 protein.

As a possible solution to combat this, the scientists added heparin, a drug used to stop blood clotting, to the simulations. They saw that it prevented PF4 from sticking to the vaccine particle.

The researchers then carried out cell-based experiments to confirm the results from the ARBD modeling.

When asked if the same clotting mechanism could be responsible for the complications associated with the J&J adenovirus-based vaccine, manuscript first author Dr. Alexander Baker replied:

“I think it’s a bit early to say this is the main/only driver. That being said, yes, we did show Adenovirus type 26 capsid (J&J) can also bind to PF4 with a similar affinity.”

What this means for the future

Study co-lead, Dr. Abhishek Singharoy, assistant professor in the School of Molecular Sciences at Arizona State University, said, “It’s really critical to fully investigate the vector-host interactions of the vaccine at a mechanistic level…[T]his will assist in understanding both how the vaccine generates immunity, and how it may lead to any rare adverse events, such as [vaccine-induced immune thrombotic thrombocytopenia] VITT.”

However, some important questions remain:

• Why does TTS occur in such a small number of vaccinated people?
• Do these findings mean that scientists can reengineer the vaccine to prevent TTS?
• Can scientists reduce the negative charge of the vaccine particle?
• Clinically, can we predict which people are at higher risk from TTS, and can we develop alternative modified vaccines to prevent clots for these high risk individuals?

Despite these questions, Dr. Raghav Palankar, a researcher at the Institute of Immunology and Transfusion Medicine in Germany, has called the research “Quite a game-changing fundamental discovery with significant translational implications.”

Source: Medical News Today