Can't sleep on time? 'Night owl' gene variant may be to blame

April 7, 2017

Washington, Apr 7: If you've been a night owl all your life and mornings are your nemesis, blame a gene mutation for keeping you awake, scientists say. Researchers at Rockefeller University in the US have discovered that a variant of the gene CRY1 slows the internal biological clock - called the circadian clock - that normally dictates when you feel sleepy each night and when you are ready to wake.sleep

People with the "night owl" variant of this gene have a longer circadian cycle than most, making them stay awake later, researchers said. "Compared to other mutations that have been linked to sleep disorders in just single families worldwide, this is a fairly impactful genetic change," said Michael W Young, professor at Rockefeller.

According to the new research, the mutation may be present in as many as one in 75 people in some populations. Sleep or wakefulness disorder - ranging from insomnia to narcolepsy - can predispose people to chronic diseases including diabetes, obesity and depression. People who self-categorise as night owls are often diagnosed with delayed sleep phase disorder (DSPD).

Their 24 hour sleep-wake cycle is delayed, making them energetic long after most people have fallen asleep. Going to bed late has its downsides: most people with DSPD are forced to wake up before their bodies tell them to in order to make it to work or school on time, leading not only to insomnia early in the night, but also to fatigue during the day.

To find out whether mutations in any known circadian genes were linked to DSPD, subjects were asked to spend two weeks in a laboratory apartment that was isolated from all cues to the time of day, eating and sleeping whenever they were inclined. Researchers also collected skin cells from each person. Most people will follow a roughly 24 hour sleep-wake cycle when put in such a free-run environment.

However, a DSPD subject that caught the researcher's interest not only stayed up late, but had a cycle that was about 30 minutes longer. Moreover, changes in body temperature and hormones that cycle along with the circadian clock - including melatonin, which helps regulate sleep - were also delayed.

"Melatonin levels start to rise around 9 or 10 at night in most people. In this DSPD patient that doesn't happen until 2 or 3 in the morning," said Young. When the researchers examined the DNA from the DSPD patient, one variant stood out; a mutation in CRY1, a gene that had already been implicated in the circadian cycle.

In a healthy circadian clock, a handful of genes turn on and off over a 24 hour cycle. The protein made by CRY1 is normally responsible for suppressing some of these genes during certain parts of the cycle. However, researchers discovered that the mutation identified in the patient made the CRY1 protein more active than usual, keeping other clock genes switched off for a longer period of time.

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Agencies
July 2,2020

The American pharmaceutical giant Pfizer Inc. and the European biotechnology company BioNTech SE have conducted an experimental trial of a COVID-19 vaccine candidate and found it to be safe, well-tolerated, and capable of generating antibodies in the patients.

The study, which is yet to be peer-reviewed, describes the preliminary clinical data for the candidate vaccine -- nucleoside-modified messenger RNA (modRNA), BNT162b1.

It said the amount of antibodies produced in participants after they received two shots of the vaccine candidate was greater than that reported in patients receiving convalescent plasma from recovered COVID-19 patients.

"I was glad to see Pfizer put up their phase 1 trial data today. Virus neutralizing antibody titers achieved after two doses are greater than convalescent antibody titers," tweeted Peter Hotez, a vaccine scientist from Baylor College of Medicine in the US, who was unrelated to the study.

Researchers, including those from New York University in the US, who were involved in the study, said the candidate vaccine enables human cells to produce an optimised version of the receptor binding domain (RBD) antigen -- a part of the spike (S) protein of SARS-CoV-2 which it uses to gain entry into human cells.

"Robust immunogenicity was observed after vaccination with BNT162b1," the scientists noted in the study.

They said the program is evaluating at least four experimental vaccines, each of which represents a unique combination of mRNA format and target component of the novel coronavirus, SARS-CoV-2.

Based on the study's findings, they said BNT162b1 could be administered in a quantity that was well tolerated, potentially generating a dose dependent production of immune system molecules in the patients.

The research noted that patients treated with the vaccine candidate produced nearly 1.8 to 2.8 fold greater levels of RBD-binding antibodies that could neutralise SARS-CoV-2.

"We are encouraged by the clinical data of BNT162b1, one of four mRNA constructs we are evaluating clinically, and for which we have positive, preliminary, topline findings," said Kathrin U. Jansen, study co-author and Senior Vice President and Head of Vaccine Research & Development, Pfizer.

"We look forward to publishing our clinical data in a peer-reviewed journal as quickly as possible," Jansen said.

According to Ugur Sahin, CEO and Co-founder of BioNTech, and another co-author of the study, the preliminary data are encouraging as they provide an initial signal that BNT162b1 is able to produce neutralising antibody responses in humans.

He said the immune response observed in the patients treated with the experimental vaccine are at, or above, the levels observed from convalescent sera, adding that it does so at "relatively low dose levels."

"We look forward to providing further data updates on BNT162b1," Sahin said.

According to a statement from Pfizer, the initial part of the study included 45 healthy adults 18 to 55 years of age.

It said the priliminary data for BNT162b1 was evaluated in 24 subjects who received two injections of 10 microgrammes ( g) and 30 g -- 12 subjects who received a single injection of 100 g, and 9 subjects who received two doses of a dummy vaccine.

The study noted that participants received two doses, 21 days apart, of placebo, 10 g or 30 g of BNT162b1, or received a single dose of 100 g of the vaccine candidate.

According to the scientists, the highest neutralising concentrations of antibodies were observed seven days after the second dose of 10 g, or 30 g on day 28 after vaccination.

They said the neutralising concentrations were 1.8- and 2.8-times that observed in a panel of 38 blood samples from people who had contracted the virus.

In all 24 subjects who received two vaccinations at 10 g and 30 g dose levels, elevation of RBD-binding antibody concentrations was observed after the second injection, the study noted.

It said these concentrations are 8- and 46.3-times the concentration seen in a panel of 38 blood samples from those infected with the novel coronavirus.

At the 10 g or 30 g dose levels, the scientists said adverse reactions, including low grade fever, were more common after the second dose than the first dose.

According to Pfizer, local reactions and systemic events after injection with 10 g and 30 g of BNT162b1 were "dose-dependent, generally mild to moderate, and transient."

It said the most commonly reported local reaction was injection site pain, which was mild to moderate, except in one of 12 subjects who received a 100 g dose, which was severe.

The study noted that there was no serious adverse events reported by the patients.

Citing the limitations of the research, the scientists said the immunity generated in the participants in the form of the T cells and B cells of their immune system, and the level of immunity needed to protect one from COVID-19 are unknown.

With these preliminary data, along with additional data being generated, Pfizer noted in the statement that the two companies will determine a dose level, and select among multiple vaccine candidates to seek to progress to a large, global safety and efficacy trial, which may involve up to 30,000 healthy participants if regulatory approval to proceed is received.

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Agencies
June 23,2020

The record levels of new daily COVID-19 cases are due to the fact that the pandemic is peaking in a number of big countries at the same time and reflect a change in the virus' global activity, the World Health Organisation said.

At a media briefing on Monday, WHO's emergencies chief Dr Michael Ryan said that the numbers are increasing because the epidemic is developing in a number of populous countries at the same time.

Some countries have attributed their increased caseload to more testing, including India and the US But Ryan dismissed that explanation.

We do not believe this is a testing phenomenon, he said, noting that numerous countries have also noted marked increases in hospital admissions and deaths neither of which cannot be explained by increased testing.

There definitely is a shift in that the virus is now very well established, Ryan said. The epidemic is now peaking or moving towards a peak in a number of large countries.

He added the situation was definitely accelerating in a number of countries, including the US and others in South Asia, the Middle East and Africa.

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Agencies
August 2,2020

Washington, Aug 2: Children under the age of five have between 10 to 100 times greater levels of genetic material of the coronavirus in their noses compared to older children and adults, a study in JAMA Pediatrics said Thursday.

Its authors wrote this meant that young children might be important drivers of Covid-19 transmission within communities -- a suggestion at odds with the current prevailing narrative.

The paper comes as the administration of US President Donald Trump is pushing hard for schools and daycare to reopen in order to kickstart the economy.

Between March 23 and April 27, researchers carried out nasal swab tests on 145 Chicago patients with mild to moderate illness within one week of symptom onset.

The patients were divided into three groups: 46 children younger than five-years-old, 51 children aged five to 17 years, and 48 adults aged 18 to 65 years.

The team, led by Dr Taylor Heald-Sargent of the Ann & Robert H. Lurie Children's Hospital, observed, "a 10-fold to 100-fold greater amount of SARS-CoV-2 in the upper respiratory tract of young children."

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The authors added that a recent lab study had demonstrated that the more viral genetic material was present, the more infectious virus could be grown.

It has also previously been shown that children with high viral loads of the respiratory syncytial virus (RSV) are more likely to spread the disease.

"Thus, young children can potentially be important drivers of SARS-CoV-2 spread in the general population," the authors wrote.

"Behavioral habits of young children and close quarters in school and daycare settings raise concern for SARS-CoV-2 amplification in this population as public health restrictions are eased," they concluded.

The new findings are at odds with the current view among health authorities that young children -- who, it has been well established, are far less likely to fall seriously ill from the virus -- don't spread it much to others either.

However, there has been fairly little research on the topic so far.

One recent study in South Korea found children aged 10 to 19 transmitted Covid-19 within households as much as adults, but children under nine transmitted the virus at lower rates.

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