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‘Zombie’ genes? Research shows some genes come to life in the brain after death: Post-mortem changes may shed light on important brain studies
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In the hours after we die, certain cells in the human brain are still active. Some cells even increase their activity and grow to gargantuan proportions, according to new research from the University of Illinois Chicago.
What’s significant, Loeb said, is the implications of this discovery — most research studies that use postmortem human brain tissues to find treatments and potential cures for disorders such as autism, schizophrenia and Alzheimer’s disease, do not account for the post-mortem gene expression or cell activity.
“”Most studies assume that everything in the brain stops when the heart stops beating, but this is not so,” Loeb said. “”Our findings will be needed to interpret research on human brain tissues. We just haven’t quantified these changes until now.”
Loeb and his team noticed that the global pattern of gene expression in fresh human brain tissue didn’t match any of the published reports of postmortem brain gene expression from people without neurological disorders or from people with a wide variety of neurological disorders, ranging from autism to Alzheimer’s”We decided to run a simulated death experiment by looking at the expression of all human genes, at time points from 0 to 24 hours, from a large block of recently collected brain tissues, which were allowed to sit at room temperature to replicate the postmortem interval,” Loeb said.
Loeb and colleagues are at a particular advantage when it comes to studying brain tissue. Loeb is director of the UI NeuroRepository, a bank of human brain tissues from patients with neurological disorders who have consented to having tissue collected and stored for research either after they die, or during standard of care surgery to treat disorders such as epilepsy. For example, during certain surgeries to treat epilepsy, epileptic brain tissue is removed to help eliminate seizures. Not all of the tissue is needed for pathological diagnosis, so some can be used for research. This is the tissue that Loeb and colleagues analyzed in their research.
They found that about 80% of the genes analyzed remained relatively stable for 24 hours — their expression didn’t change much. These included genes often referred to as housekeeping genes that provide basic cellular functions and are commonly used in research studies to show the quality of the tissue. Another group of genes, known to be present in neurons and shown to be intricately involved in human brain activity such as memory, thinking and seizure activity, rapidly degraded in the hours after death. These genes are important to researchers studying disorders like schizophrenia and Alzheimer’s disease, Loeb said.
A third group of genes — the ‘zombie genes’ — increased their activity at the same time the neuronal genes were ramping down. The pattern of post-mortem changes peaked at about 12 hours.
“”Our findings don’t mean that we should throw away human tissue research programs, it just means that researchers need to take into account these genetic and cellular changes, and reduce the post-mortem interval as much as possible to reduce the magnitude of these changes,” Loeb said. “”The good news from our findings is that we now know which genes and cell types are stable, which degrade, and which increase over time so that results from postmortem brain studies can be better understood.””
Fabien Dachet, Tibor Valyi-Nagy, Kunwar Narayan, Anna Serafini and Gayatry Mohapatra of UIC; James Brown and Susan Celniker of Lawrence Berkeley National Laboratory; Nathan Boley of the University of California, Berkeley; and Thomas Gingeras of Cold Spring Harbor Laboratory are co-authors on the paper.
This research was funded by grants from the National Institutes of Health (R01NS109515, R56NS083527, and UL1TR002003).
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‘Ice bucket challenge’ reveals that bacteria can anticipate the seasons
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Bacteria use their internal 24-hour clocks to anticipate the arrival of new seasons, according to research carried out with the assistance of an ‘ice bucket challenge.’
The team behind the findings gave populations of blue-green algae (cyanobacteria) different artificial day lengths at a constant warm temperature. Samples on plates received either short days, equinox days (equal light and dark), or long days, for eight days.
After this treatment, the blue-green algae were plunged into ice for two hours and survival rates monitored.
Samples that had been exposed to a succession of short days (eight hours light and 16 hours dark) in preparation for the icy challenge achieved survival rates of 75%, up to three times higher than colonies that had not been primed in this way.
One short day was not enough to increase the bacteria’s resistance to cold. Only after several short days, and optimally six to eight days, did the bacteria’s life chances significantly improve.
In cyanobacteria which had genes that make up their biological clock removed, survival rates were the same regardless of day lengths. This indicates that photoperiodism (the ability to measure the day-night cycle and change one’s physiology in anticipation of the upcoming season) is critical in preparing bacteria for longer-term environmental changes such as a new season or shifts in climate.
“The findings indicate that bacteria in nature use their internal clocks to measure day length and when the number of short days reaches a certain point, as they do in autumn/fall, they ‘switch’ to a different physiology in anticipation of the wintry challenges that lie ahead,” explained first author of the study, Dr Luísa Jabbur, who was a researcher at Vanderbilt University, Tennessee, in the laboratory of Prof. Carl Johnson when this study took place, and is now a BBSRC Discovery Fellow at the John Innes Centre.
The Johnson lab has a long history of studying the circadian clock of cyanobacteria, both from a mechanistic and an ecological perspective.
Previous studies have shown that bacteria have a version of a biological clock, which could allow them to measure differences in day-night length, offering an evolutionary advantage.
This study, which appears in Science, is the first time that anyone has shown that photoperiodism in bacteria has evolved to anticipate seasonal cues.
Based on these findings a whole new horizon of scientific exploration awaits. A key question is: how does an organism with a lifespan of between six and 24 hours evolve a mechanism that enables it not merely to react to, but to anticipate, future conditions?
“It’s like they are signalling to their daughter cells and their granddaughter cells, passing information that the days are getting short, you need to do something,” said Dr Jabbur.
Dr Jabbur and colleagues at the John Innes Centre will, as part of her BBSRC Discovery Fellowship, use cyanobacteria as a fast-reproducing model species to understand how photoperiodic responses might evolve in other species during climate change, with hopeful applications to major crops.
A key part of this work will be to understand more about the molecular memory systems by which information is passed from generation to generation in species. Research will investigate the possibility that an accumulation of compounds during the night on short days acts as a molecular switch that triggers change to a different physiology or phenotype.
For Dr Jabbur the findings amount to an early-career scientific breakthrough in the face of initial scepticism from her scientific mentor and the corresponding author of the paper, Professor Carl Johnson.
“As well as being a fascinating person and an inspiration, Carl sings in the Nashville Symphony Chorus, and he has an operatic laugh! It echoed round the department when I first outlined my idea for the icy challenge, to see if photoperiod was a cue for cyanobacteria in their natural element,” said Dr Jabbur.
“To be fair he told me to go away and try it, and as I went, he showed me a sign on his door with the Frank Westheimer quote: ‘Progress is made by young scientists who carry out experiments that old scientists say would not work.’
“It did work, first time. Then I repeated the experiments. There is something very precious about looking at a set of plates with bacteria on them and realizing that in that moment you know something that nobody else knows.”
Bacteria can anticipate the seasons: Photoperiodism in cyanobacteria appears in Science.
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New filtration material could remove long-lasting chemicals from water
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Water contamination by the chemicals used in today’s technology is a rapidly growing problem globally. A recent studyby the U.S. Centers for Disease Control found that 98 percent of people tested had detectable levels of PFAS, a family of particularly long-lasting compounds, also known as forever chemicals, in their bloodstream.
The findings are described in the journal ACS Nano, in a paper by MIT postdoc Yilin Zhang, professor of civil and environmental engineering Benedetto Marelli, and four others from MIT.
PFAS chemicals are present in a wide range of products, including cosmetics, food packaging, water-resistant clothing, firefighting foams, and antistick coating for cookware. A recent study identified 57,000 sites contaminated by these chemicals in the U.S. alone. The U.S. Environmental Protection Agency has estimated that PFAS remediation will cost $1.5 billion per year, in order to meet new regulations that call for limiting the compound to less than 7 parts per trillion in drinking water.
Contamination by PFAS and similar compounds “is actually a very big deal, and current solutions may only partially resolve this problem very efficiently or economically,” Zhang says. “That’s why we came up with this protein and cellulose-based, fully natural solution,” he says.
“We came to the project by chance,” Marelli notes. The initial technology that made the filtration material possible was developed by his group for a completely unrelated purpose — as a way to make a labelling system to counter the spread of counterfeit seeds, which are often of inferior quality. His team devised a way of processing silk proteins into uniform nanoscale crystals, or “nanofibrils,” through an environmentally benign, water-based drop-casting method at room temperature.
Zhang suggested that their new nanofibrillar material might be effective at filtering contaminants, but initial attempts with the silk nanofibrils alone didn’t work. The team decided to try adding another material: cellulose, which is abundantly available and can be obtained from agricultural wood pulp waste. The researchers used a self-assembly method in which the silk fibroin protein is suspended in water and then templated into nanofibrils by inserting “seeds” of cellulose nanocrystals. This causes the previously disordered silk molecules to line up together along the seeds, forming the basis of a hybrid material with distinct new properties.
By integrating cellulose into the silk-based fibrils that could be formed into a thin membrane, and then tuning the electrical charge of the cellulose, the researchers produced a material that was highly effective at removing contaminants in lab tests.
The electrical charge of the cellulose, they found, also gave it strong antimicrobial properties. This is a significant advantage, since one of the primary causes of failure in filtration membranes is fouling by bacteria and fungi. The antimicrobial properties of this material should greatly reduce that fouling issue, the researchers say.
“These materials can really compete with the current standard materials in water filtration when it comes to extracting metal ions and these emerging contaminants, and they can also outperform some of them currently,” Marelli says. In lab tests, the materials were able to extract orders of magnitude more of the contaminants from water than the currently used standard materials, activated carbon or granular activated carbon.
While the new work serves as a proof of principle, Marelli says, the team plans to continue working on improving the material, especially in terms of durability and availability of source materials. While the silk proteins used can be available as a byproduct of the silk textile industry, if this material were to be scaled up to address the global needs for water filtration, the supply might be insufficient. Also, alternative protein materials may turn out to perform the same function at lower cost.
Initially, the material would likely be used as a point-of-use filter, something that could be attached to a kitchen faucet, Zhang says. Eventually, it could be scaled up to provide filtration for municipal water supplies, but only after testing demonstrates that this would not pose any risk of introducing any contamination into the water supply. But one big advantage of the material, he says, is that both the silk and the cellulose constituents are considered food-grade substances, so any contamination is unlikely.
“Most of the normal materials available today are focusing on one class of contaminants or solving single problems,” Zhang says. “I think we are among the first to address all of these simultaneously.”
The research team included MIT postdocs Hui Sun and Meng Li, graduate student Maxwell Kalinowski, and recent graduate Yunteng Cao PhD ’22, now a postdoc at Yale. The work was supported by the Office of Naval Research, the National Science Foundation, and the Singapore-MIT Alliance for Research and Technology.
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‘Some pterosaurs would flap, others would soar’ — new study further confirms the flight capability of these giants of the skies
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Some species of pterosaurs flew by flapping their wings while others soared like vultures, demonstrates a new study published in the peer-reviewed Journal of Vertebrate Paleontology.
However, “remarkable” and “rare” three-dimensional fossils of two different large-bodied azhdarchoid pterosaur species — including one new-to-science — have enabled scientists to hypothesize that not only could the largest pterosaurs take to the air, but their flight styles could differ too.
The new findings are led by experts from the University of Michigan, in the US, the Natural Resources Authority and Yarmouk University, in Jordan, and the Saudi Geological Survey, in Saudi Arabia.
Their paper details how these fossils — which date back to the latest Cretaceous period (approximately 72 to 66 million years ago) — were remarkably three-dimensionally preserved within the two different sites that preserve a nearshore environment on the margin of Afro-Arabia, an ancient landmass that included both Africa and the Arabian Peninsula. The research team used high-resolution computed tomography (CT) scans to then analyze the internal structure of the wing bones.
“The dig team was extremely surprised to find three-dimensionally preserved pterosaur bones, this is a very rare occurrence,” explains lead author Dr Kierstin Rosenbach, from the Department of Earth and Environmental Sciences of the University of Michigan.
“Since pterosaur bones are hollow, they are very fragile and are more likely to be found flattened like a pancake, if they are preserved at all.
“With 3D preservation being so rare, we do not have a lot of information about what pterosaur bones look like on the inside, so I wanted to CT scan them.
“It was entirely possible that nothing was preserved inside, or that CT scanners were not sensitive enough to differentiate fossil bone tissue from the surrounding matrix.”
Luckily, though, what the team uncovered was “remarkable,” via “exciting internal structures not only preserved, but visible in the CT scanner.”
CT scans reveal one soars; one flaps!
Newly collected specimens of the already-known giant pterosaur, Arambourgiania philadelphiae, confirm its 10-meter wingspan and provide the first details of its bone structure. CT images revealed that the interior of its humerus, which is hollow, contains a series of ridges that spiral up and down the bone.
This resembles structures in the interior of wing bones of vultures. The spiral ridges are hypothesized to resist the torsional loadings associated with soaring (sustained powered flight that requires launch and maintenance flapping).
The other specimen analyzed was the new-to-science Inabtanin alarabia, which had a five-meter wingspan. The team named it after the place where it was excavated — near a large grape-colored hill, called Tal Inab. The generic name combines the Arabic words “inab,” for grape, and “tanin” for dragon. ‘Alarabia’ refers to the Arabian Peninsula.
Inabtanin is one of the most complete pterosaurs ever recovered from Afro-Arabia, and the CT scans revealed the structure of its flight bones was completely different from that of Arambourgiania.
The interior of the flight bones were crisscrossed by arrangement with struts that match those found in the wing bones of modern flapping birds.
This indicates it was adapted to resist bending loads associated with flapping flight, and so it is likely that Inabtanin flew this way — although this does not preclude occasional use of other flight styles too.
“The struts found in Inabtanin were cool to see, though not unusual,” says Dr Rosenbach.
“The ridges in Arambourgiania were completely unexpected, we weren’t sure what we were seeing at first!
“Being able to see the full 3D model of Arambourgiania’s humerus lined with helical ridges was just so exciting.”
What explains this difference?
The discovery of diverse flight styles in differently-sized pterosaurs is “exciting,” the experts state, because it opens a window into how these animals lived. It also poses interesting questions, like to what extent flight style is correlated with body size and which flight style is more common among pterosaurs.
“There is such limited information on the internal bone structure of pterosaurs across time, it is difficult to say with certainty which flight style came first,” Dr Rosenbach adds.
“If we look to other flying vertebrate groups, birds and bats, we can see that flapping is by far the most common flight behavior.
“Even birds that soar or glide require some flapping to get in the air and maintain flight.
“This leads me to believe that flapping flight is the default condition, and that the behavior of soaring would perhaps evolve later if it were advantageous for the pterosaur population in a specific environment; in this case the open ocean.”
Co-author Professor Jeff Wilson Mantilla, Curator at Michigan’s Museum of Paleontology, and Dr Iyad Zalmout, from the Saudi Geological Survey, found these specimens in 2007 at sites in the north and south of Jordan.
Professor Jeff Wilson Mantilla says the “variations likely reflect responses to mechanical forces applied on the pterosaurs’ wings during flight.”
Enabling further study of vertebrate flight
Concluding, Dr Rosenbach states: “Pterosaurs were the earliest and largest vertebrates to evolve powered flight, but they are the only major volant group that has gone extinct.
“Attempts to-date to understand their flight mechanics have relied on aerodynamic principles and analogy with extant birds and bats.
“This study provides a framework for further investigation of the correlation between internal bone structure and flight capacity and behavior, and will hopefully lead to broader sampling of flight bone structure in pterosaur specimens.”
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