How malaria parasites withstand heat

EVEN when a person suffering from malaria is burning up with fever and too sick to function, the tiny blood-eating parasites lurking inside them continue to flourish, relentlessly growing and multiplying as they gobble up the host’s red blood cells.
The single-celled Plasmodium parasites that cause 200 million cases of malaria each year can withstand feverish temperatures that make their human hosts miserable. And now, a Duke University-led team is beginning to understand how they do it.
Assistant professor of chemistry Emily Derbyshire and colleagues have identified a lipid-protein combo that springs into action to gird the parasite’s innards against heat shock.
Understanding how the malaria parasite protects its cells against heat stress and other onslaughts could lead to new ways to fight resistant strains, which have evolved ways to survive the drugs traditionally used to kill them, the researchers say.
Nearly half of the world’s population is at risk of contracting malaria. The disease kills 400,000 people a year, most of them children.
Long before the cause of malaria was identified, the disease’s harrowing fevers were well known. References to them have been found on 5,000-year-old clay tablets from ancient Mesopotamia. The Greek poet Homer wrote about their misery. Hippocrates too. The Duke team, collaborating with professor of biological engineering Jacquin Niles at the Massachusetts Institute of Technology, wanted to know how the malaria parasites inside a person’s body make it through these fevers unscathed.
When the parasites enter a person’s bloodstream through the bite of an infected mosquito, the temperature around them jumps from the balmy mid-70s of the mosquito to 98.6 degrees in the human. The human host’s body temperature can then rocket to 105 degrees or higher before dropping back down to normal two to six hours later, a roller coaster pattern that repeats itself every two to three days.
“It’s like going from room temperature water to a hot tub,” said first author Kuan-Yi Lu, who earned his PhD in molecular genetics and microbiology in Derbyshire’s lab at Duke.
For the paper, published on Sept 25 in the journal eLife, Lu spent hundreds of hours peering at parasites under the microscope, trying to figure out what happens inside them when temperatures seesaw. To mimic malarial fever in the lab, the researchers placed malaria-infected red blood cells in an incubator heated to 104 degrees Fahrenheit for six hours before bringing them back down to normal body temperature, 98.6 degrees.
They found that when temperatures rise, the parasites produce more of a lipid molecule called phosphatidylinositol 3-phosphate, or PI(3)P.
This substance builds up in the outer wall of a tiny sac inside the parasite’s cells called the food vacuole — the protist’s version of a gut. There, it recruits and binds to another molecule, a heat shock protein called Hsp70, and together they help shore up the food vacuole’s outer walls. –Science Daily

Research reveals that increase in waist circumference is associated with higher risk of all-cause mortality.

A smaller belly may a mean longer life

CENTRAL fatness (excess fat stored around the abdomen) is associated with a higher risk of early death from any cause, regardless of overall body fat, whereas larger hips and thighs are associated with a lower risk, finds a study published recently.
The results suggest that measuring central fatness may be a more reliable indicator of risk of death from excess weight, and could be used alongside body mass index (BMI) to help determine the risk of premature death, say the researchers.
BMI is a simple measure widely used to assess people’s weight. But, its reliability is often criticised, as it does not distinguish fat from muscle and does not tell us where body fat is stored.
It is already well-known that being overweight or obese is linked to a greater risk of heart disease, certain cancers, kidney disease, and neurological disorders.
Evidence also suggests that central fatness might be more strongly associated with risk of death than overall obesity, but previous data are inconclusive.
To explore this further, an international team of researchers set out to examine whether measures of central fatness are associated with risk of all-cause mortality in the general population.
Their findings are based on the results of 72 studies involving over 2.5 million participants who were tracked for between three and 24 years.
All of the studies reported risk estimates for at least three measures of central fatness.
These included waist circumference, hip circumference, thigh circumference, waist-to-hip ratio, waist-to-height ratio, waist-to-thigh ratio, body adiposity index (a measure of total body mass made only of fat tissue), and A body shape index (a combined measure of body height, mass and waist circumference).
The researchers found that most measures of abdominal adiposity, including waist circumference, waist-to-hip ratio, waist-to-height ratio, waist-to-thigh ratio, and A body shape index were significantly and positively associated with a higher mortality risk.
For example, each 10cm increase in waist circumference was associated with an 11 per cent higher risk of all-cause mortality, while every 0.1 unit increase in waist-to-hip ratio, waist-to-height ratio, and waist-to-thigh ratio was associated with a 20 per cent higher risk.
In contrast, larger hip and thigh circumference were associated with a lower risk of mortality.
For example, each 10cm increase in hip circumference was associated with a 10 per cent lower risk of all-cause mortality, while each 5cm increase in thigh circumference was associated with an 18 per cent lower risk.
The researchers note that these associations remained significant after accounting for BMI. -The Star
This suggests that abdominal deposition of fat, independent of overall obesity, is associated with a higher risk.
They point to some limitations, such as the possibility that some studies may have included patients with undiagnosed pre-existing disease.
However, strengths include the high quality of the studies and large number of participants across different populations.
As such, the researchers say their results suggest that “measures of central adiposity could be used as a supplementary approach, in combination with BMI, to determine the risk of premature death.”
And they say further studies are needed to assess the degree and the shape of the associations for these measures in more detail. –The Star

Using Excel caused Covid-19 results loss

THE badly thought-out use of Microsoft’s Excel software was the reason nearly 16,000 coronavirus cases went unreported in England.
And it appears that Public Health England (PHE) was to blame, rather than a third-party contractor.
The issue was caused by the way the agency brought together logs produced by commercial firms paid to analyse swab tests of the public, to discover who has the virus.
They filed their results in the form of text-based lists – known as CSV files – without issue.
PHE had set up an automatic process to pull this data together into Excel templates so that it could then be uploaded to a central system and made available to the NHS Test and Trace team, as well as other government computer dashboards.
The problem is that PHE’s own developers picked an old file format to do this – known as XLS.
As a consequence, each template could handle only about 65,000 rows of data rather than the one million-plus rows that Excel is actually capable of.
And since each test result created several rows of data, in practice it meant that each template was limited to about 1,400 cases.
When that total was reached, further cases were simply left off.
For a bit of context, Excel’s XLS file format dates back to 1987. It was superseded by XLSX in 2007. Had this been used, it would have handled 16 times the number of cases.
At the very least, that would have prevented the error from happening until testing levels were significantly higher than they are today,
But one expert suggested that even a high-school computing student would know that better alternatives exist.
“Excel was always meant for people mucking around with a bunch of data for their small company to see what it looked like,” commented Prof Jon Crowcroft from the University of Cambridge.
“And then when you need to do something more serious, you build something bespoke that works – there’s dozens of other things you could do. But you wouldn’t use XLS. Nobody would start with that.”
Speaking in the House of Commons, the Health Secretary Matt Hancock suggested that the problem had emerged as a result of PHE using a “legacy system” and a decision had been taken two months ago to replace it.
Presumably, however, this specific problem had not been spotted. Otherwise PHE would have realised that the flaw would come into effect before the upgrade was complete.
Mr Hancock was challenged to put other relevant data-process diagrams into the public domain, so other hidden failings in the government’s digital apparatus could be found.
But while the minister said he would see what was possible, he added: “The challenge of a maximum file size error is that it wouldn’t necessarily appear on those sorts of flowcharts.”
PHE is confident that test results were not missed until last week, because of the flaw. And in its defence, the agency would note that it caught most of the cases within a day or two of the records slipping through its net. But Labour’s shadow health secretary Jonathan Ashworth said lives had still been put at risk because the contact-tracing process had been delayed.
“Thousands of people [were] blissfully unaware they’ve been exposed to Covid, potentially spreading this deadly virus at a time when hospital admissions are increasing,” he told the House of Commons. –BBC

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