Researchers at Baylor College of Medicine, Shandong University in China and other institutions may have found an explanation for dawn phenomenon, an abnormal increase of blood sugar only in the morning, observed in many patients with type 2 diabetes. They report in the journal Nature that mice lacking the circadian clock gene called Rev-erb in the brain show characteristics similar to those of dawn phenomenon.
The researchers then looked at Rev-erb gene expression in patients with type 2 diabetes comparing a group with dawn phenomenon to a group without it and found that the gene’s expression followed a different temporal pattern between these two groups. The findings support the idea that an altered daily rhythm of expression of the Rev-erb gene may underlie dawn phenomenon. Future investigations may lead to therapies.
“We began this study to investigate what was the function of Rev-erb in the brain,” said co-corresponding author Dr. Zheng Sun, associate professor of medicine-endocrinology, diabetes and metabolism at Baylor. “We are interested in this gene because it is a ‘druggable’ component of the circadian clock with potential applications in the clinic. Rev-erb is expressed only during the day but not at night. When we started, we did not know where this was going to lead us.”
The researchers first developed a mouse model by knocking out the Rev-erb gene in GABA neurons. They chose this approach because the gene’s expression is highly enriched in a particular brain area called the suprachiasmatic nucleus that is mainly composed of GABA neurons.
An unexpected finding
“We observed something very interesting in these mice,” Sun said. “They were glucose intolerant — that is they had high glucose levels — only in the evening. Mice are nocturnal, meaning that they become active in the evening as people do in the morning.”
When the body awakes and takes in food, insulin is secreted from the pancreas to signal the body to lower blood sugar. Insulin is more effective in doing this job upon waking than at other times of the day. This high insulin sensitivity is probably because the body is anticipating feeding behaviors upon waking up. In mice, high insulin sensitivity occurs in the evening, while in people it occurs in the morning.

Researchers at Lund University in Sweden have investigated how the X and Y chromosomes evolve and adapt to each other within a population. The results show that breaking up coevolved sets of sex chromosomes could lead to lower survival rates among the offspring — something that could be of importance in species conservation, for example. The study is published in the journal PNAS.
The results provide new clues on how species are formed, and suggest it could be harmful to bring together individuals from different populations that have been separated for a long time. The reason is that the offspring have lower survival rates.
“This is something worth keeping in mind in conservation biology, where you want to see a population grow,” says Jessica Abbott, researcher in evolutionary ecology at Lund University.
It is previously known that hybrids between different species often do better if they are female (two X chromosomes) rather than male (X and Y chromosome).
In the study, the researchers crossed fruit flies from five different populations from different continents in order to combine X and Y chromosomes with different origins. They then followed and studied the subsequent generations.
The results show that males with X and Y chromosomes that don’t match had higher reproductive success than males with matching X and Y chromosomes. However, the higher male fertility was paired with lower survival rates among their offspring.
“We were expecting the opposite, that males with different origin X and Y chromosomes would have lower reproductive success, so that was surprising,” says Jessica Abbott.
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Other drug makers have begun similar trials of their Covid-19 vaccines. If they work in children younger than 12 as expected, it will be easier for the U.S. to reach herd immunity.Pfizer has begun testing its Covid-19 vaccine in children under 12, a significant step in turning back the pandemic. The trial’s first participants, a pair of 9-year-old twin girls, were immunized at Duke University in North Carolina on Wednesday.Results from the trial are expected in the second half of the year, and the company hopes to vaccinate younger children early next year, said Sharon Castillo, a spokeswoman for the pharmaceutical company.Moderna also is beginning a trial of its vaccine in children six months to 12 years of age. Both companies have been testing their vaccines in children 12 and older, and expect those results in the next few weeks.AstraZeneca last month began testing its vaccine in children six months and older, and Johnson & Johnson has said it plans to extend trials of its vaccine to young children after assessing its performance in older children.Immunizing children will help schools to reopen as well as help to end the pandemic, said Dr. Emily Erbelding, an infectious diseases physician at the National Institutes of Health who oversees testing of Covid-19 vaccines in special populations.An estimated 80 percent of the population may need to be vaccinated for the United States to reach herd immunity, the threshold at which the coronavirus runs out of people to infect. Some adults may refuse to be vaccinated, and others may not produce a robust immune response.Children under 18 account for about 23 percent of the population in the United States, so even if a vast majority of adults opt for vaccines, “herd immunity might be hard to achieve without children being vaccinated,” Dr. Erbelding said.Pfizer had initially said it would wait for data from older children before starting trials of its vaccine in children under 12. But “we were encouraged by the data from the 12 to 15 group,” said Ms. Castillo, who did not elaborate on the results so far.Scientists will test three doses of the Pfizer vaccine — 10, 20 and 30 micrograms — in 144 children. Each dose will be assessed first in children 5 through 11 years of age, then in children ages 2 through 4 years, and finally in the youngest group, six months to 2 years.After determining the most effective dose, the company will test the vaccine in 4,500 children. About two-thirds of the participants will be randomly selected to receive two doses 21 days apart; the remaining will get two placebo shots of saline. The researchers will assess the children’s immune response in blood drawn seven days after the second dose.“It sounds like a good plan, and it’s exciting that another Covid-19 vaccine is moving forward with trials in children,” said Dr. Kristin Oliver, a pediatrician and vaccine expert at Mount Sinai Hospital in New York.Dr. Oliver said about half of the parents she sees in practice are eagerly waiting for vaccines, and even to volunteer their children for clinical trials, while the rest are skeptical because comparatively few children become seriously ill from coronavirus infection.Both groups of parents will benefit from knowing exactly how safe and effective the vaccines are in children, she said.Children represent 13 percent of all reported cases in the United States. More than 3.3 million children have tested positive for the virus, at least 13,000 have been hospitalized and at least 260 have died, noted Dr. Yvonne Maldonado, who represents the American Academy of Pediatrics on the federal Advisory Committee on Immunization Practices.The figures do not fully capture the damage to children’s health. “We don’t know what the long-term effects of Covid infection are going to be,” Dr. Maldonado said.Other vaccines have helped to control many horrific childhood diseases that can cause long-term complications, she added: “For some of us who’ve seen that, we don’t want to go back to those days.”Children often react more strongly to vaccines than adults do, and infants and toddlers in particular can experience high fevers. Any side effects are likely to appear soon after the shot, within the first week and certainly within the first few weeks, experts have said.Some vaccines are tested only in animals before being assessed in children, and have to be monitored carefully for side effects.“But this is a little different, because we’ve already had experience with tens of millions of people with these vaccines,” Dr. Maldonado said. “So there’s a higher degree of confidence now in giving this vaccine to kids.”Some experts suggested that the Food and Drug Administration may require up to six months of safety data from studies of children before authorizing the Covid-19 vaccines. But a spokeswoman said the agency did not expect six months of safety data to support the vaccines’ authorization.The Pfizer-BioNTech vaccine is authorized for children 16 through 18 years old, and the authorization for that age group was based on just two months of safety data, she said.Parents will want to know how the companies and the F.D.A. plan to monitor and disclose side effects from the vaccines, and how long they will continue to follow trial participants after the vaccines’ authorization, Dr. Oliver said.“I think everyone has learned throughout this,” she said. “The more transparent you can be, the better.”

A new study conducted at the Galveston National Laboratory at the The University of Texas Medical Branch at Galveston (UTMB) has shown substantial benefit to combining monoclonal antibodies and the antiviral remdesivir against advanced Marburg virus. The study was published today in Nature Communications.
“Marburg is a highly virulent disease in the same family as the virus that causes Ebola. In Africa, patients often arrive to a physician very ill. It was important to test whether a combination of therapies would work better with really sick people, said Tom Geisbert, a professor in the Department of Microbiology & Immunology at UTMB and the principal investigator for the study. “Our data suggests that this particular combination allowed for recovery when given at a very late stage of disease.”
Dr. Zachary A. Bornholdt, Senior Director of Antibody Discovery and Research for Mapp Biopharmaceutical and a co-author on the study, said, “Often small molecules and antibodies are positioned to compete with each other for a single therapeutic indication. Here we see the benefit of pursuing both treatment strategies in tandem and ultimately finding synergy upon combining both approaches together.”
Geisbert, Bornholdt and a large team at UTMB, Mapp Biopharmaceuticals and Gilead have been developing monoclonal antibody (mAbs) therapies to treat extremely dangerous viruses like Marburg and Ebola for several years. The treatments have proven to be highly effective in laboratory studies and emergency use, particularly when delivered early in the disease course.
In this study, using a rhesus model, treatment with monoclonal antibodies began six days post infection, a critical point in disease progression. The combination therapy with the antiviral remdesivir showed an 80 percent protection rate, indicating promise for treatment of advanced Marburg infections.
The study was supported by the Department of Health and Human Services, National Institutes of Health grant U19AI142785 and UC7AI094660 for BSL-4 operations support of the Galveston National Laboratory.
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Early screening can mean the difference between life and death in a cancer and disease diagnosis. That’s why University of Central Florida researchers are working to develop a new screening technique that’s more than 300 times as effective at detecting a biomarker for diseases like cancer than current methods.
The technique, which was detailed recently in the Journal of the American Chemical Society, uses nanoparticles with nickel-rich cores and platinum-rich shells to increase the sensitivity of an enzyme-linked immunosorbent assay (ELISA).
ELISA is a test that measures samples for biochemicals, such as antibodies and proteins, which can indicate the presence of cancer, HIV, pregnancy and more. When a biochemical is detected, the test generates a color output that can be used to quantify its concentration. The stronger the color is, the stronger the concentration. The tests must be sensitive to prevent false negatives that could delay treatment or interventions.
In the study, the researchers found that when the nanoparticles were used in place of the conventional enzyme used in an ELISA — peroxidase — that the test was 300 times more sensitive at detecting carcinoembryonic antigen, a biomarker sometimes used to detect colorectal cancers.
And while a biomarker for colorectal cancer was used in the study, the technique could be used to detect biomarkers for other types of cancers and diseases, says Xiaohu Xia, an assistant professor in UCF’s Department of Chemistry and study co-author.
Colorectal cancer is the third leading cause of cancer-related deaths in the U.S., not counting some kinds of skin cancer, and early detection helps improve treatment outcomes, according to the U.S. Centers for Disease Control and Prevention.

The glow of a panther’s eyes in the darkness. The zig-zagging of a shark’s dorsal fin above the water.
Humans are always scanning the world for threats. We want the chance to react, to move, to call for help, before danger strikes. Our cells do the same thing.
The innate immune system is the body’s early alert system. It scans cells constantly for signs that a pathogen or dangerous mutation could cause disease. And what does it like to look for? Misplaced genetic material.
The building blocks of DNA, called nucleic acids, are supposed to be hidden away in the cell nucleus. Diseases can change that. Viruses churn out genetic material in parts of the cell where it’s not supposed to be. Cancer cells do too.
“Cancer cells harbor damaged DNA,” says Sonia Sharma, Ph.D., an associate professor at the La Jolla Institute for Immunology (LJI). “Mislocated DNA or aberrant DNA is a danger signal to the cell. They tell the cell, ‘There’s a problem here.’ It’s like the first ringing of the alarm bell for the immune system.”
Now Sharma and her colleagues have published a new Nature Immunology study describing the process that triggers this alert system directly inside tumor cells. Their research shows that a tumor-suppressor enzyme called DAPK3 is an essential component of a multi-protein system that senses misplaced genetic material in tumor cells, and slows tumor growth by activating the fierce-sounding STING pathway.

Officials want to investigate whether the vaccine is related to blood clots and other rare but dangerous problems.Denmark will extend its suspension of the AstraZeneca vaccine until April 15, the Danish Health Authority announced on Thursday, as other European countries are restarting use of the vaccine.Officials in Denmark want to further investigate whether AstraZeneca vaccine is the cause of an unusual disease picture involving low blood platelets, bleeding and blood clots in unexpected places in the body, the head of the Danish Health Authority, Soren Brostrom, said.The European Medical Agency, the continent’s top drug regulator, said last week that it had found no sign of the vaccine causing such rare but dangerous problems, and strong evidence that its lifesaving benefits “outweigh the risk of the side effects.”The agency announced on Thursday that it was convening a group of external medical experts to help assess the safety of the vaccine.Denmark was the first country to suspend use of the AstraZeneca vaccine, on March 11. It has reported two deaths from brain hemorrhages among people who had received the shot.Officials acknowledged that continuing the suspension would lead to delays in the vaccination process.“We are very conscious that a continued hold on vaccination with the Covid-19 vaccine from AstraZeneca delays the Danish vaccination program,” Mr. Brostrom said. “However, the vaccines are already in the refrigerator. If we decide to recommence vaccination with the Covid-19 vaccine from AstraZeneca, we can quickly distribute and use the vaccines.”The health authorities in Sweden, which last week suspended the use of the AstraZeneca vaccine, said on Thursday that the country would resume its use for people over 65.In other developments around the world:Schools in Romania will close for four weeks starting next month as the Eastern European country fights to curb its latest wave of Covid-19 cases. Most schools will close from April 2 to May 4, Sorin Cimpeanu, Romania’s education minister, said on Thursday, extending the usual break for Orthodox and Catholic Easter.Travelers flying to Germany will need to show proof they tested negative for Covid-19 before boarding flights starting on Sunday, the country’s health ministry said on Thursday. Germans rushed to book flights and hotels in Portugal and Spain for Easter and Holy Week holidays after the government took those nations off its “at risk” list that require people to quarantine upon return to Germany.

Alzheimer’s disease seems to progress faster in women than in men. The protein tau accumulates at a higher rate in women, according to research from Lund University in Sweden. The study was recently published in Brain.
Over 30 million people suffer from Alzheimer’s disease worldwide, making it the most common form of dementia. Tau and beta-amyloid are two proteins known to aggregate and accumulate in the brain in patients with Alzheimer’s.
The first protein to aggregate in Alzheimer’s is beta-amyloid. Men and women are equally affected by the first disease stages, and the analysis did not show any differences in the accumulation of beta-amyloid. Memory dysfunction arises later, when tau starts to accumulate. More women than men are affected by memory problems due to Alzheimer’s, and it was for tau that the researchers found a higher rate of accumulation in women.
“Tau accumulation rates vary greatly between individuals of the same sex, but in the temporal lobe, which is affected in Alzheimer’s disease, we found a 75% higher accumulation rate in women as a group compared to men,” explains Ruben Smith, first author of the study.
The accumulation of tau is faster in patients who already have a pathological accumulation of beta-amyloid, and are in the early phase of the disease. The discovery that the accumulation rate of tau is higher in women remained even after adjusting for age and the levels of tau they had at the beginning. Together with data from three similar cohorts in the USA, the project contains 209 women and 210 men.
“The next step would be to examine why this accumulation is faster in women,” says Sebastian Palmqvist, the researcher responsible for the cognitive assessment of the patients.
The study did not investigate the reasons for the higher rate of tau accumulation in women.
“Our study strongly indicates that the faster spread of tau makes women more prone to develop dementia because of Alzheimer’s pathology compared to men. Future experimental studies will be important to understand the reasons behind this,” concludes Professor Oskar Hansson.
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Influenza vaccines need to be evaluated every year to ensure they remain effective against new influenza viruses. Will the same apply to COVID-19 vaccines? In order to gauge whether and to what extent this may be necessary, a team of researchers from Charité — Universitätsmedizin Berlin compared the evolution of endemic ‘common cold’ coronaviruses with that of influenza viruses. The researchers predict that, while the pandemic is ongoing, vaccines will need to undergo regular updates. A few years into the post-pandemic period, however, vaccines are likely to remain effective for longer. This study has been published in Virus Evolution.
Influenza viruses are masters at evading the human immune system. They undergo such rapid changes that antibodies produced by the immune system in response to a previous infection or vaccination become unable to neutralize them. This is why the complex task of evaluating and updating the seasonal influenza vaccine has to be repeated every year. Mutations within SARS-CoV-2 have already produced a number of variants, some of which (such as the South African variant) partially evade the body’s immune response. As a result, some vaccine manufacturers have already started to develop new versions of their vaccines. What does this mean for the future? Will COVID-19 vaccines mirror influenza vaccines in requiring regular updates?
In order to gauge whether, over the long term, SARS-CoV-2 is likely to demonstrate an immune evasion capability on par with that of influenza viruses, Charité virologists have studied the genetic evolution of the four currently known ‘common cold’ coronaviruses. These relatively harmless coronaviruses are known to be responsible for approximately 10 percent of common colds in the world and have been in circulation in humans significantly longer than SARS-CoV-2. Just like SARS-CoV-2, they enter human cells using the ‘spike protein’, a surface protein which gives the virus its characteristic crown-like appearance (and name). The spike protein also forms the target of all current COVID-19 vaccines.
For their study, the researchers focused on the two longest-known coronaviruses (termed 229E and OC43), tracing changes in the spike gene approximately 40 years into the past. The researchers started by comparing sequences from a range of old samples which had been deposited in a genetic sequence data bank. Based on the mutations which had emerged over time, they then produced phylogenetic trees for both coronaviruses. The researchers compared their findings with the phylogenetic tree of H3N2, an influenza subtype which is particularly effective at evading the human immune response.
The researchers’ calculations revealed one feature which was common to the phylogenetic reconstructions of both the coronaviruses and the influenza virus: all three had a pronounced ladder-like shape. “An asymmetrical tree of this kind likely results from the repeated replacement of one circulating virus variant by another which carried a fitness advantage,” explains the study’s first author, Dr. Wendy K. Jó from Charité’s Institute of Virology. “This is evidence of ‘antigenic drift’, a continuous process involving changes to surface structures which enable viruses to evade the human immune response. It means that these endemic coronaviruses also evade the immune system, just like the influenza virus. However, one also has to look at the speed with which this evolutionary adaptation happens.”
For this step, the researchers determined the three viruses’ evolutionary rates. While the influenza virus accumulated 25 mutations per 10,000 nucleotides (genetic building blocks) per year, the coronaviruses accumulated approximately 6 such mutations in the same timeframe. The rate of change of the endemic coronaviruses was therefore four times slower than that of the influenza virus. “As far as SARS-CoV-2 is concerned, this is good news,” summarizes Prof. Dr. Christian Drosten, Director of the Institute of Virology and a researcher at the German Center for Infection Research (DZIF).
SARS-CoV-2 is currently estimated to change at a rate of approximately 10 mutations per 10,000 nucleotides per year, meaning the speed at which it evolves is substantially higher than that of the endemic coronaviruses. “This rapid genetic change in SARS-CoV-2 is reflected in the emergence of numerous virus variants across the globe,” explains study lead Prof. Dr. Jan Felix Drexler, a researcher at both the Institute of Virology and the DZIF. “This, however, is likely due to the high rates of infection seen during the pandemic. When infection numbers are so high, a virus is able to evolve more rapidly. Based on the rates of evolution seen in the endemic common cold coronaviruses, we expect that SARS-CoV-2 will start to change more slowly once infections start to die down — meaning once a large proportion of the global population has developed immunity either as a result of infection or through vaccination. We expect therefore that COVID-19 vaccines will need to be monitored regularly throughout the pandemic and updated where necessary. Once the situation has stabilized, vaccines are likely to remain effective for longer.”
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Cholinesterase inhibitors are a group of drugs recommended for the treatment of Alzheimer’s disease, but their effects on cognition have been debated and few studies have investigated their long-term effects. A new study involving researchers from Karolinska Institutet in Sweden and published in the journal Neurology shows persisting cognitive benefits and reduced mortality for up to five years after diagnosis.
Alzheimer’s disease is a cognitive brain disease that affects millions of patients around the world. Some 100,000 people in Sweden live with the diagnosis, which has a profound impact on the lives of both them and their families. Most of those who receive a diagnosis are over 65, but there are some patients who are diagnosed in their 50s.
The current cost of care and treatment for people with dementia is approximately SEK 60 billion a year in Sweden. This is on a par with the cost of care and treatment of cardiovascular diseases and is twice as high as cancer care.
In Alzheimer’s disease changes to several chemical neurotransmitters in the brain are found, and thus to the ability of the neurons to communicate with each other. Acetylcholine is one such substance and plays a key role in cognitive functions such as memory, attention and concentration.
There are three drugs that work as cholinesterase inhibitors and that are used in the treatment of Alzheimer’s disease: galantamine, donepezil and rivastigmine.
The effects of cholinesterase inhibitors have, however, been debated, partly because there are relatively few longitudinal clinical studies. Researchers at Karolinska Institutet and Umeå University have now conducted a registry study of patients with Alzheimer’s disease over a period of five years from point of diagnosis.
The study is based on data from SveDem (the Swedish Dementia Registry) on 11,652 patients treated with cholinesterase inhibitors and a matched control group of 5,826 untreated patients.
The results showed that treatment with cholinesterase inhibitors was associated with slower cognitive decline over five years, and 27 per cent lower mortality in patients with Alzheimer’s disease compared with the controls.
“Of all three drugs, galantamine had the strongest effect on cognition, which may bedue to its effect on nicotine receptors and its inhibiting effect on the enzyme acetylcholinesterase, which breaks down the neurotransmitter acetylcholine,” says the study’s first author Hong Xu, postdoctoral researcher at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet.
“Our results provide strong support for current recommendations to treat people with Alzheimer’s disease with cholinesterase inhibitors, but also shows that the therapeutic effect lasts for a long time,” says the study’s last author and initiator Maria Eriksdotter, professor at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet.
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