Tag Archives: proteins

Researchers successfully reverse aging — in a lab dish

Researchers at the Stanford University School of Medicine have successfully de-aged human cells in a lab dish.

Image via Pixabay.

Carefully exposing human cells to Yamanaka factors, proteins involved in embryonic development that are used to transform adult cells into induced pluripotent stem (or iPS) cells, can reverse cellular aging. The authors report that old human cells in a lab dish treated with these proteins were nearly indistinguishable from fresh cells.

Ageback

“We are very excited about these findings,” said study co-author Thomas Rando, MD, Ph.D., the director of Stanford’s Glenn Center for the Biology of Aging. “My colleagues and I have been pursuing the rejuvenation of tissues since our studies in the early 2000s revealed that systemic factors can make old tissues younger.”

The authors explain that iPS cells produced from adult cells become “youthful” in the process. They wondered whether the process could be stopped mid-way, in order to make the cells more vigorous without causing them to revert back to a stem state. They found that it is possible, but the procedure hinges on carefully controlling the duration of exposure to Yamanaka factors. The team can use their approach to “promote rejuvenation in multiple human cell types,” explains Vittorio Sebastiano, Ph.D. the senior author of the study.

The factors gradually wipe a cell’s genetic material clean of the bits that differentiate them — those that make a skin cell and a blood cell different, for example — and revert them back to a younger state over the course of weeks. Instead, the team only allowed exposure to continue for a few days. They then compared the genetic activity of these cells with untreated cells from both elderly adults and younger participants.

The treated cells showed signs of age reversal after four days of exposure, the team explains, and their patterns of gene expression were similar to those seen in cells from younger participants. Treated cells appeared to be about one-and-a-half to three-and-a-half years younger on average than untreated cells from elderly people. The maximum values were three and a half years for skin cells and seven and a half years for cells lining blood vessels (when comparing methylation levels, a hallmark of cell aging).

“We saw a dramatic rejuvenation across all hallmarks but one in all the cell types tested,” Sebastiano said. “But our last and most important experiment was done on muscle stem cells. Although they are naturally endowed with the ability to self-renew, this capacity wanes with age. We wondered, Can we also rejuvenate stem cells and have a long-term effect?”

The team transplanted treated muscle cells back into old mice, and reported that they regained muscle strength comparable to that of younger mice. The process also helped cells from the cartilage of people (with and without osteoarthritis) reduce the secretion of inflammatory molecules, improve cellular function, and the cells’ ability to divide.

“Although much more work needs to be done, we are hopeful that we may one day have the opportunity to reboot entire tissues,” Sebastiano said. “But first we want to make sure that this is rigorously tested in the lab and found to be safe.”

Fiber mat.

Scientists manage to keep proteins ‘alive’ outside cells

Researchers from the US have developed a method that allows them to keep proteins ‘alive’ outside of cells. The discovery paves the way for advanced materials that have the same functionality as living organisms — for example, mats that scrub air clean of chemical pollution.

Fiber mat.

Image credits Christopher DelRe, Charley Huang/UC Berkeley

Proteins don’t much like living outside of cells. We know this because researchers have been trying to get proteins stable in other environments for years now, but with very limited success. Efforts to combine these proteins with synthetic materials and still keep them functional for any length of time met a similar fate.

A new paper, however, details a method that can be used to keep these proteins active in synthetic environments, finally allowing researchers to cash in on their activity on demand.

Problems

Proteins are the heavy lifters of biochemistry. Quite literally — its constricting proteins that make your muscles, and by extension, you, move. But take them outside of the cozy place we call ‘the body’ and they fall apart quite easily. Even if they somehow survive, it doesn’t mean they will actually be doing anything. One of their most significant limitations is that proteins need to be folded just right for them to work; often, this means other proteins have to come in and do the folding.

In order to work around that problem, the team analyzed protein sequences, folding patterns, and various surfaces to see if they could develop a polymer that would cater to the proteins’ needs — to keep their structures unaltered, and thus maintain function.

“Proteins have very well-defined statistical pattern, so if you can mimic that pattern, then you can marry the synthetic and natural systems, which allows us to make these materials,” says first author Brian Panganiban.

The next step was to create random heteropolymers, or RHPs. Thpotentey’re basically the same things as a polymer (plastics), but instead of using a single type of ‘brick’ (molecules known as monomers), they use two or more different, but similar monomers. The RHPs the team developed used four types or monomers, with each being tailored to chemically interact with spots of interest along the proteins. The monomers were connected in such a way as to mimic the structure of natural proteins to help these interactions flow smoothly.

Researchers at Northwestern University simulated the molecule and its interaction with proteins of interest and determined that the material led to correct protein folding and would maintain protein stability outside living cells.

Filter me this

So far so good, but the team wanted to go beyond simulations and test their results in real life. They decided to use the RHPs and proteins to construct bioremediation filters. The protein they chose for the job was organophosphorus hydrolase (OPH), which degrades toxic organic-phosphate compounds, such as those found in insecticides or chemical warfare agents.

They spun the RHP/OPH into fiber mats and submersed them in insecticide. The mats degraded an amount of insecticide weighing approximately one-tenth of the mat’s weight in just a few minutes. The team says the mats are easily scalable and can be customized with different proteins meaning their technology could be used for a wide range of applications. In fact, at least part of the funding for this research came from the US Department of Defense — the mats can be used to soak up chemical weapons in war zones, to scrub contaminated areas, even as on-demand, handheld filters.

“We think we’ve cracked the code for interfacing natural and synthetic systems,” says co-author Ting Xu, a professor at the University of California, Berkeley.

Despite the interest shown by military planners, the mats show great potential in the bioremediation of areas polluted with chemical contamination events. Because RHPs can be customized with a wide range of proteins — which means a wide range of substances they can interact with, and several ways to do so — Xu’s team believes their work could form the basis for portable chemistry labs of the future, a fast response team for potential environmental contamination events.

The paper “Random heteropolymers preserve protein function in foreign environments” has been published in the journal Science.

Nightshift.

Just two days of night-shift alter the activity of more than 100 blood proteins

Sleeping during the day and staying up all night will impact the concentration and activity of over 100 proteins in the blood — even if you only do it for short while.

Nightshift.

Image credits picsessionarts / Flickr.

Staying awake and eating during the night throws a wrench in the activity of blood-borne proteins, according to new research from the University of Colorado Boulder. The proteins identified by the team impact processes involved in a wide array of metabolic functions, from blood sugar levels to immune function. The study is the first to examine how protein levels in human blood, also known as the plasma proteome, vary over a 24-hour period and how altered sleep and meal timing affects them.

Protein shift

“This tells us that when we experience things like jet lag or a couple of nights of shift work, we very rapidly alter our normal physiology in a way that if sustained can be detrimental to our health,” said senior author Kenneth Wright, director of the Sleep and Chronobiology Laboratory and Professor in the Department of Integrative Physiology.

The team enlisted the help of six healthy male subjects in their 20s for the study. The participants were asked to spend six days at the university’s clinical translational research center. While here, their meals, sleeping hours, active periods and the hours they were exposed to light were tightly controlled and recorded.

On the first two days, the men were kept on a normal schedule: active hours and light exposure during the day, sleeping hours at night. They were then gradually transitioned to a night-shift work pattern —  they could get an eight-hour sleep if they wanted, but only during the day, and stayed up and ate at night. The team collected blood samples every four hours, which they analyzed for the concentrations and time-of-day-patterns of 1,129 proteins.

They report that 129 of these proteins’ patterns were thrown off by the simulated night shift. The effect was already noticeable by the second day of night-shift waking patterns, Depner adds.

One of the affected proteins was glucagon — which tells the liver to inject sugar into the bloodstream. Glucagon levels in the blood peaked during waking hours, the team found, meaning they shifted to night-hours as the participants started staying awake at night. But it also peaked in higher concentrations, the team adds. They think that this effect could, in the long-term, form the root cause of the higher diabetes rates seen in night-shift workers.

Night-shift wakefulness patterns also decreased blood levels of fibroblast growth factor 19. Previous research with animal models has shown this protein to boost calorie-burning and energy expenditure, the team adds. The participants in this study burned 10% fewer calories per minute when their schedule was misaligned.

Overall, thirty proteins showed a clear 24-hour-cycle, most showing a peak between 2 p.m. and 9 p.m.

“The takeaway: When it comes to diagnostic blood tests—which are relied upon more often in the age of precision medicine—timing matters,” said senior author Kenneth Wright.

The authors note that all the participants were kept in dim light conditions, to eliminate the effect of light-exposure (which can also strongly affect the circadian system) on the results. Even without the glow of electronics at night, changes in protein patterns were rapid and widespread.

“This shows that the problem is not just light at night,” Wright said. “When people eat at the wrong time or are awake at the wrong time that can have consequences too.”

The findings could lead to new treatment options for night shift workers, who are at a higher risk for diabetes and cancer. It could also enable doctors to precisely time administration of drugs, vaccines and diagnostic tests around the circadian clock.

The paper “Mistimed food intake and sleep alters 24-hour time-of-day patterns of the human plasma proteome” has been published in the journal PNAS.

Blood cells.

Cosmonaut blood reveals that our immune systems grind to a halt in space

Millions of years of evolution may have rendered us Earth-locked, a Canadian-Russian research team reports. Zero- and microgravity conditions seem to severely impair our immune systems’ ability to function, so much so that they’d struggle to deal with even minor viruses like that of the common cold.

Blood cells.

Image credits BagoGames / Flickr.

A team of Russian and Canadian researchers have analyzed the protein make-up in the blood of 18 Russian cosmonauts to get an idea of their immune system health. They report that the crew, who spent six months aboard the International Space Station, showed signs of significantly weakened immune systems that would struggle to deal even with minor pathogens.

No gravity, no service

“The results showed that in weightlessness, the immune system acts like it does when the body is infected because the human body doesn’t know what to do and tries to turn on all possible defense systems,” said Professor Evgeny Nikolaev of the Moscow Institute of Physics and Technology, the Skolkovo Institute of Science and Technology, and paper coresponding author.

Our bodies, like those of all other organisms on Earth, have been tailored by evolution to adapt to specific conditions. It makes perfect evolutionary sense to adapt to the place you’re living in, but humans are now trying to do something that no life before us ever tried — we want to leave the planet. That’s quite problematic since it takes us out of the set of conditions we’re designed to function in.

Environmental factors associated with spaceflight, most notably microgravity and radiation exposure, tend to mess up our bodies’ inner workings. Our metabolism, heat regulation systems, heart rhythm, muscle tone, bone density, vision, our respiratory systems, they all go a bit haywire once you take us off the planet.

It all adds up to take a toll. Astronauts who went on deep space or lunar missions were five times more likely to die from cardiovascular diseases than their counterparts who stayed in low orbit, or people who never left Earth (around 43% compared to under 10% for the latter). And that’s considering that astronauts are way fitter than the average Joe and have access to the best medical care available.

To get a better idea of how space travel impacts human physiology, the team looked at the level of 125 proteins in the blood of astronauts who spent six months aboard the ISS. Proteins underpin virtually all complex tasks inside the body, so by looking at their state in the blood researchers could infer the state of the crew’s immune systems. Samples were first taken from the cosmonauts 30 days before they left for the ISS to establish a baseline. To track changes in their immune systems, the team also took blood samples immediately after the cosmonauts returned to Earth, and seven days later. Individual proteins were counted using a mass spectrometer.

The results aren’t very encouraging at all

”When we examined the cosmonauts after their being in space for half a year, their immune system was weakened,” said Dr Irina Larina, the first author of the paper, a member of Laboratory of Ion and Molecular Physics of Moscow Institute of Physics and Technology.

“They were not protected from the simplest viruses. We need new measures of disorder prevention during a long flight.

It doesn’t bode well for future explorers, as our immune system is what’s literally keeping us alive all day, every day. The effects were manageable, although severe, after only six months. But future missions are likely going to take much longer. A one-way trip to Mars, our closest viable candidate for a colony, would take around six to eight months — and colonists wouldn’t have the medical means and infrastructure available on Earth, meaning they’ll have to rely on their now weakened immune systems much more than the cosmonauts. So it can become a problem.

However, we can get to work on understanding and then address these changes before we start poking around the final frontier.

“We must understand the mechanism that causes disorders. If we find the pathways that are affected by the weightlessness, we will be able to find the target for the remedy and we’ll be able to offer new pharmaceutical products that will prevent these negative processes.”

The paper “Protein expression changes caused by spaceflight as measured for 18 Russian cosmonauts” has been published in the journal Nature Scientific Reports.

Wheat.

What is gluten and why some people have gluten intolerance

“Gluten” is an umbrella term used to denote the mix of storage protein compounds found in all species and hybrids of wheat and its related grains (barley, rye, etc). Not a single substance but rather a mixture of various kinds of protein, gluten is, simply put, the way these cereals store building materials for the future.

Wheat.

*gluten intensifies*
Image credits Hans Braxmeier.

Owing to proteins’ tendency to bunch up or string together, gluten lends elasticity and texture to baked goods, making them either chewy or crunchy — “gluten” is actually the Latin word for “glue”. It’s also the object of many a fad diet and legitimate dietary concerns (primarily in the shape of allergies or intolerances), and a cool compound to use in making DIY playdough.

What is gluten made of

So right off the bat, gluten doesn’t have a set chemical structure. Its composition varies depending on the species in question and the exact percentages very likely differ from individual to individual. But in a general sense, gluten is a mixture of prolamins and glutelins.

Prolamins are a family of storage proteins used to stockpile (mainly) proline and glutamine, two amino acids which underpin protein synthesis for plants. Each crop produces and stores a different brand of prolamin — gliadin in wheat, hordein for barley, secalin in rye, zein in corn, kafirin in sorghum, and avenin (minor protein) in oats. Glutelins do basically the same thing as prolamins in chemically-different combinations and shapes. They’re rich in amino acids, particularly glutenin (wheat), though to a lesser overall degree than prolamins.

Proline&Glutamine.

The two amino acids gluten mainly stores.

All plants use protein stores of one kind or another, mostly concentrated in fruits in the case of endosperms, earmarked to supply budding plants during germination. The term gluten is sometimes extended to these stores as well (especially for corn or rice as they’re also cereals) but true gluten (with prolamins and glutelins) is only found in wheat, its related grains, and their species and hybrids. Some other gluten-free grains you’re likely to bump or bite into are quinoa, amaranth, and oats — although this last one is usually not recommended by dietitians, as it’s usually processed through the same channels as wheat-related grains, which can contaminate it with gluten.

Why gluten is good

Proline is considered to be a non-essential amino acid in the human body (the need can be covered by internal synthesis), while glutamine plays a non-essential/conditionally essential role (it is usually supplied by the body’s own synthesis processes, but must be supplemented by diet in certain stressful conditions). Glutamine has the distinction of being the most abundant free amino acid in the bloodstream.

So while they do have nutritional value, for the most part, our bodies don’t really need these amino acids. But gluten plays a central part in how we process and then consume grains. It accounts for the lion’s share of proteins in bread — anywhere between 75 to 80% — so to understand what it does, let’s take a quick look at how these behave.

Bread.

Those stretch-like marks are made by gluten holding the dough together during yeast fermentation.
Image credits Lebensmittelfotos.

Proteins are essentially long chains of amino acids strewn together and folded into certain shapes. They do all sorts of stuff in living bodies, such as pumping compounds in and out of cells or moving things around. But the thing we’re interested in right now is that they are also the go-to compounds when mechanical resilience and stiffness are required. Your nails are so hard compared to your skin because they’re rich in keratin. Your nose never breaks because elastin strands hold the cartilage together, just like the iron rods do in reinforced concrete. Cells keep their shape because tiny filaments of protein run from wall to wall and prop them up.

And that’s what gluten does in pretty much any foodstuff made from flour. By kneading it with water, bakers “weave” gluten into long elastic strands which act similarly to those of a polymer. These strands are made up of glutenin molecules which criss-cross into a microscopic net-like pattern along with gliadin (wheat glutenin) molecules, making the dough hold together, feel a bit rubbery, and stretchable. Heat treatment such as baking or boiling breaks the folding in gluten and makes it coagulate, which, along with starch, gives bread its mechanical properties. Gluten has also been identified as playing a part in the staling of bread, likely by binding atmospheric water molecules.

To get an idea of the physical properties of gluten and how it ties food together, you can play around with a lump of pure gluten. It’s quite fun — keep your hands clean and (most of) you can eat it afterward, too. If you don’t have any lying around, tofu is a similar product (soy/plant proteins but with a higher % of fat mixed in) which is more widely available.

What is gluten intolerance

Now, my reaction to hearing about a new fad diet is a wide smile and a knowing, paternal chuckle. And a big part of the demand for gluten-free products comes down to just that — a fad. To each his own (wallet) but, considering a number of foodstuffs that have gluten and their nutritional value, going gluten-free without any medical reason isn’t the best of ideas as it could end up making your diet way worse overall.

At least some people have a sense of humor about it.
Image credits William Murphy / Flickr.

That being said, some people who are gluten-sensitive or gluten-intolerant can’t eat gluten. There are several gluten-related disorders: celiac disease (CD) is the most common form of intolerance, then there’s the still-debated-on non-celiac gluten sensitivity (NCGS), and a slew of other nasty reactions from dermatitis herpetiformis and irritable bowel syndrome (IBS) to gluten ataxia and wheat allergy. People suffering from CD see their bodies produce an abnormal immune response when digesting gluten, making their digestive tract unable to absorb nutrients. About 18 million Americans have gluten sensitivity, according to the National Foundation for Celiac Awareness. Those with NCGS exhibit many of the same symptoms, due to poor digestion or a placebo effect, still under debate. So why does this happen?

The first thing you have to keep in mind is that while humans are omnivores, our bodies just aren’t geared to eating absolutely everything out there — but we’re very good at adapting. Certain populations overcome diet limitations over time through contact with traditional types of food.

For example, Western society as a whole is much less lactose intolerant than the rest of, well, mammals, since in nature milk is reliably on the menu only before weaning — after that, it’s highly unlikely to pop up, so mammalian bodies don’t maintain a stock of lactase because it doesn’t make economic sense for them to do so. But most westerners today have acquired lactose resistance through (relatively few) generations of natural selection for the ability to eat dairy, as milk was an important source of nutrients here. Writing in the New York time on this subject, Moises Velasquez-Manoff said:

“Few Scandinavian hunter-gatherers living 5,400 years ago had lactase persistence genes, for example. Today, most Scandinavians do.”

The “we’re not yet adapted to it” approach has a lot of support, and there may be some limited validity to that point of view in certain cases. We know of grain consumption even before agriculture, albeit on a reduced scale. It’s also likely that those cereals were poorer in gluten or might not have employed it all together (such as is the case with wild oats), meaning there was no reason to adapt to eating a lot of grains by that time. There is evidence tying CD to genetic factors. However, I’d say that adaptation similar to the one above led to a greater digestibility of gluten and likely worked up a natural tolerance for the majority of humans — else people wouldn’t have eaten it for like 23,000 years.

One other factor cited to play a hand in gluten intolerance is that selective breeding of wheat and related crops up to modern times led to increasing levels of ATIs (-α-amylase/trypsin inhibitors), which the plants use to fight off insects but also interfere with the digestive tract’s processing of gluten, and our bodies are still catching up to that. But research doesn’t point to any increase in ATIs.

One final factor may be more modern — after the transition to agriculture, the genes which cause autoimmune disorders may have provided an evolutionary advantage by keeping people extra-safe in the crowded, pathogen-rich environments of early settlements. And we’re seeing an overall increase in autoimmune disorders of every kind recently as more of the slack is taken away from our immune systems by drugs, making it liable to react out of proportion to perceived threats.

The bottom line is that we don’t really know where gluten intolerance stems from yet.

As for the other disorders, their causes vary quite a lot and may not even be understood or still debated in some cases. If you think you may have a form of gluten sensibility, speaking to a physician is your best way of getting more information.

Cool stuff gluten can do for you

You can still have some fun with gluten, even if you can’t eat it. Candia on Instructables has a nice guide set up so you can make some at home. The cream of tartar will make the dough more elastic, but even if you take it our of the mix the gluten is strong enough to keep the play-dough in one piece no matter how you stretch it. It’s basically dough so you don’t have to worry about the kids (or yourself) sneaking a bite out of it — but be mindful of intolerance.

If you’d rather feel like gluing your kids to the wall (I don’t judge), Wheatglue can come in handy. It’s as easy as mixing flour and water, as Instructabler theRIAA shows. It’s one of the oldest glues ever, used since antiquity to bind books and in the more modern art of plastering posters. Plus, it’s biodegradable so the little ones will come off on their own after some time.

This is not chicken — seriously. It’s seitan, which is basically gluten. The broccoli is just broccoli. Image credits: John / Flickr.

You can use gluten as an alternative to tofu (seitan) and will likely appreciate its more robust texture and stronger aroma compared to the subtle soy product. And as a bonus for vegetarians, you’ll finally have a go-to answer for when people ask where you get your protein from. It even looks a lot like meat, and it’s much healthier than tofu.

So is gluten right for you? Well, statistically speaking, probably yes.

Cells nudge each other with proteins when moving to keep your body in one piece

A new signaling mechanism that epithelial cells use to communicate during motion has been uncovered, explaining how individual (or groups of) cells can move inside of a tissue without compromising its structure.

Image credits Umberto Salvagnin / Flickr.

One cell left to its own devices can move about pretty easily if needed. Its motion is similar to a ‘flow’ of sorts, with the cell’s leading edge extending a protrusion and its trailing edge drawing itself along. The same process of motion is used by cells included in tissues, with the extra requirement that the overall structure remains intact. So how do these tiny bits of life communicate and co-ordinate their motions in the context of tissues?

Protein nudges

When you need to pass through a tightly-packed group of people, your best bet is to communicate your intention of moving forward (verbally or through nudging) so they’ll make way. Cells in tissues do the same thing, but with proteins. Some of the signal proteins used in this process have been documented for some time now, but research from the University of Chicago has identified a new protein-driven signaling system that epithelial cells use to coordinate individual movements to move whole tissues at once.

Top view of Drosophila’s ventral cells undergoing apical constriction and invagination (cells taking on a wedge-like shape to create a cavity).
Image credits Institute Pasteur via giphy.

Cell biologist Sally Horne-Badovinac, PhD, and colleagues from the UoC found that two membrane proteins work in tandem to coordinate epithelial migration in Drosophila, the common fruit fly. The first one is called Lat, and works on the leading edge of the cell. The other, Fat2, acts at the trailing edge. Lets say we have three cells, A, B, and C, one behind the other, as the whole tissue needs to move.

For B to migrate, its Fat2 molecules first signal to the Lar behind it, which causes that cell (A) to extend its edge and go under B. In turn, B extends its leading edge under C, nudged by C’s Fat2. When A finishes its motion, its Lar signals to B’s Fat2, which retracts its leading edge — and the same happens between B and C.

Through this step-by-step process, neighboring cells can coordinate and move the whole tissue at the same time without leaving any holes in it.

“The protrusion of one cell goes underneath edge of the cell ahead, so you get what looks like overlapping shingles on a roof,” said Horne-Badovinac, an assistant professor of molecular genetics and cell biology and first author of the study.

“This process is understood really well at the single cell level, but when you hook these cells all together in a tight sheet, it becomes something more coordinated.”

The team used fruit flies to study this signaling process. As female embryos develop, the tissues which will later form egg chambers stretch and rotate into their final position. Scientists knew that both Fat2 and Lar were involved in this process, but it wasn’t clear if the cells were migrating because the tissues rotate around the circumference of a circular chamber, not moving in a straight line.

So Horne-Badovinac and her team grew the egg chambers in cell cultures outside of the female flies to get a better look at how they behaved. In groups of normal cells located behind cells edited to lack Fat2, the leading edge protrusions didn’t form. In groups of normal cells placed in front of Lar-missing patches, the trailing edges weren’t retracted.

“It was surprising, because what we knew was that the protein [Fat2] was at the trailing edge of the cell, but we were seeing an effect at the leading edge of the cell. So initially that made absolutely no sense,” said Horne-Badovinac.

“It required careful analysis along those cloned boundaries to really figure it out.”

Horne-Badovinac said there are still a lot of questions regarding the interaction between these proteins, and thinks there are other proteins which handle motion signaling to organelles inside the cell — especially the cytoskeletal machinery, which drives cellular movement.

Uncovering the mechanisms of coordinated cell movement could help us better understand critical stages of embryonic development, wound healing, and even cancer spread.

 

The full paper “Fat2 and Lar Define a Basally Localized Planar Signaling System Controlling Collective Cell Migration” has been published in the journal Developmental Cell.

Sea slugs can’t remember their dreams — and here’s why you can’t, either

Scientists identified a seemingly counterintuitive process in the brain that prevents stimuli from forming memories. This system also springs into action as you are waking up to prevent corruption of previous memories — which might explain why it’s so hard to remember what you dreamed about.

Image credits Karolina / Pexels.

Without any prior training or a handbook handy when you wake up, it’s incredibly hard (and frustrating) to try and remember what you dreamed about a few moments before. It’s like you’re grasping at a shape in the fog — you know something was there and you have a rough idea of what it was like but every time you reach out you’re met with a handful of nothing. But why is it so hard to remember?

It all comes down to how our brain forms memories. Some of the stimuli that bombards you each and every day are deemed important enough to be memorized, which our neurons do by forming connections between each other — known as “trace memories”. This, however, is only a temporary measure, since these initial connections (and so the memories they maintain) are pretty fragile. To turn them into long-term memories, the brain has to go through a process called consolidation.

This involves synthesizing proteins to strengthen trace memories. However, if new stimuli are recorded while this process takes place, they could disrupt the process or overwrite the memory trace. So you might run into all sorts of problems if your brain started consolidating willy-nilly in the middle of the day. Thankfully, it evolved to only do so at night while you’re sleeping. But just in case you wake up during consolidation, the brain has mechanisms in place to prevent you from interrupting the process.

Slugging it out for memory space

A new study by Prof. Abraham Susswein of the Mina and Everard Goodman Faculty of Life Sciences and The Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center at Bar-Ilan University has identified this mechanism. He and his colleagues studied the sea hare Aplysia who are surprisingly convenient subjects for neuroscientific studies — they have simple nervous systems made up of large neurons, and have also shown basic learning abilities.

They found that after training the slugs’ brains started producing low levels of consolidating proteins, levels which spiked when the sea slugs went to sleep. But by blocking the production of these proteins in sleeping slugs, they were able to prevent them from forming long-term memories — confirming that they too consolidate memories during sleep.

They also found that exposing the animals to stimuli as they were waking up didn’t trigger the formation of new memories — they tried training the animals after awakening them from sleep, but the slugs couldn’t learn. On awakening, their brain blocked any interaction between the stimuli and long-term memory. When treating the slugs with a drug that inhibits protein production prior to training, the slugs could generate long-term memories however.

Removing the protein block allows the formation of long-term memories of experience just after waking up — even experiences that are too brief to trigger memories in fully awake slugs.

“The major insight from this research is that there is an active process in the brain which inhibits the ability to learn new things and protects the consolidation of memories,” Susswein says.

The team also found that training sea slugs in social isolation seems to inhibit their learning abilities, and identified a similar process active in this state.

“Our next step following on from this work is to identify these memory blocking proteins and to fathom how they prevent the formation of new memories,” says Susswein,

“We may also find that the blocking process accounts for why we cannot remember our dreams when we wake up.”

One exciting possibility is that is these proteins can inhibit memory formation, they could potentially be used to block unwanted or traumatic memories such as those of PTSD patients.

The full paper “New learning while consolidating memory during sleep is actively blocked by a protein synthesis dependent process” has been published in the journal eLife.

 

Bad news for cancer cells — your immune system immunity has been revoked

Researchers have discovered why cancer cells are able to cloak themselves from the body’s immune system, allowing them to metastasize and spread throughout the body.

Cancer cells.
Image credits National Cancer Institute.

Cancer is a terrible disease. Contrary to common-held beliefs, however, it’s not a modern disease, nor is it a human-only one. It arises from genetic defects in cells’ DNA. As the tumors develop, more and more mutations are added to the cells’ genetic code.

University of British Columbia scientists have discovered that through this process, cancerous cells lose the proteic pathway used to synthesize interleukein-33. IL-33 is an intermediary in a “warning flag” complex of proteins known as the major histocompatibility complex (MHC.)

MHC proteins coat diseased or malfunctioning cells so that white blood cells know to swoop in and recycle them — so, when the IL-33 protein disappears, malignant cells look like their ordinary, healthy counterparts to our immune system. Unattacked, they grow and spread out through the body — a step known as metastasis.

“The immune system is efficient at identifying and halting the emergence and spread of primary tumours but when metastatic tumours appear, the immune system is no longer able to recognize the cancer cells and stop them,” said Wilfred Jefferies, senior author of the study working in the Michael Smith Laboratories and a professor of Medical Genetics and Microbiology and Immunology at UBC.

The team found that IL-33 loss occurs in epithelial carcinomas — cancers of organ-lining tissues. This includes prostate, kidney, breast, lung, uterine, cervical, pancreatic, and skin — among many other — types of cancer. With help from the Vancouver Prostate Centre, they studied several hundred patients and found that people suffering from prostate or kidney cancers whose tumours didn’t produce any IL-33 had more rapid recurrence of the condition over a five-year period.

When treating metastatic cancers with the protein, the patients’ immune systems jump-started and began attacking the malignant cells. The group hopes that reversing the genetic processes which rids cancers of marker proteins such as IL-33 will make them visible as targets to white blood cells again.

“IL-33 could be among the first immune biomarkers for prostate cancer and, in the near future, we are planning to examine this in a larger sample size of patients,” said Iryna Saranchova, a PhD student in the department of microbiology and immunology and first author on the study.

Researchers have been desperately searching for an effective cure for cancer, with some success (see here and here). But finding a way to make our own immune system attack tumours would definitely revolutionize how we think about this disease in the future.

The full paper “Discovery of a Metastatic Immune Escape Mechanism Initiated by the Loss of Expression of the Tumour Biomarker Interleukin-33” has been published in the journal Scientific Reports.

Research team grows “dinosaur legs” on a chicken for the first time

Researchers in Chile, studying the evolutionary link between dinosaurs and modern-day birds, have manipulated the genome of chicken embryos so that they develop dinosaur-like bones in their lower legs.

Image credits to DeviantArt user AivisV.

Most dinosaurs perished some 65 million years ago when a meteor impacted earth — but not all of them. The ones that survived gave rise to the birds we know today. To understand how this transition happened, a research team from Chile altered the genes of regular chicken so that they grow longer, tubular fibulas (the spine-like bone you’ll find in a drumstick.)

In avian dinosaurs such as Archaeopteryx, this tube-like bone reached from the knee all the way down to the ankle alongside the tibia. Bird embryos show the developmental stages for fibulas akin to those seen in Archaeopteryx but at maturity the bones are shorter, thinner and pointy towards the end, no longer reaching the ankle.

Researchers led by Joâo Botelho from the University of Chile decided to investigate how this transition from a long, tubular fibula in dinosaurs to a short, splinter-like fibula in birds took place. When they inhibited the expression of the IHH gene (short for Indian Hedgehog gene) bird embryos’ fibulas continued to grow in a similar shape to those seen in dinosaur fossils. This way, the team discovered that this bone grows — or rather, stops growing — differently than most other bones.

Usually, bone development first halts in the shaft long before the ends stop growing, but in modern chickens the fibula first stops its growth at the ends, then the center — meaning the bone is actively blocked from growing into a more dinosaur-like shape. The researchers suggest that this cessation of growth in the lower end of the fibula is prompted by a bone in the ankle, called the calcaneum.

Development of the fibula is normal during early stages of development, but then abruptly stops. Image credits João Francisco Botelho et. al./ author provided.

Development of the fibula is normal during early stages of development, but then abruptly stops. Bone on the left is the tibia.
Image credits João Francisco Botelho et. al./ author provided.

In avian dinosaurs such as the Archaeopteryx, the fibula was a tube-shaped bone that reached all the way down to the ankle. Another bone, the tibia, grew to a similar length alongside it.

“Unlike other animals, the calcaneum in bird embryos presses against the lower end of the fibula,” the team explains in a press release.

“They are so close, they have even been mistaken for a single element by some researchers.”

Image credits João Francisco Botelho et. al./ author provided.

The interaction between the calcaneum and the fibula signals the bone shaft to stop developing, essentially blocking it from reaching anywhere near the ankle. But, with the IHH gene expression blocked, the calcaneum strongly expresses the gene for Parathyroid-related protein (PthrP), which allows for growth at the ends of bones. The result — dinosaur-like fibulas, just like Archaeopteryx had.

“Experimental downregulation of IHH signalling at a postmorphogenetic stage led to a tibia and fibula of equal length,” the team writes in the report.

“The fibula is longer than in controls and fused to the fibulare, whereas the tibia is shorter and bent.”

Birds lost their long fibula as evolution selected against it in one of their direct ancestor groups — dinosaurs known as the Pygostylians.

“The experiments are focused on single traits to test specific hypotheses,” one of the team, Alexander Vargas, explains.

“Not only do we know a great deal about bird development, but also about the dinosaur-bird transition, which is well-documented by the fossil record. This leads naturally to hypotheses on the evolution of development, that can be explored in the lab.”

Last year, the same team grew dinosaur-like feet on their chickens, and a separate team in the US managed to grow a dinosaur-like ‘beak’ on its chicken embryos.

The full paper, titled “Molecular development of fibular reduction in birds and its evolution from dinosaurs” has been published online in the journal Evolution and can be read here.

 

Evolution selects the most effective genes — even by a hundredth of a percent

Evolution promotes the survival of the most adept members of a species — but exactly how much “fitter” an organism has to be, compared to its peers, to hold a selective advantage over them? A new study from Uppsala University has measured the forces that shape bacterial genomes, and determined that a difference as tiny as one hundredth of a percent is sufficient to determine the winners and losers in the evolutionary race.

The go-to phrase when trying to explain evolution in a nutshell has to be “survival of the fittest.” Interestingly enough, the phrase was coined in 1864 by British philosopher Herbert Spencer to draw a parallel between his economic theories and Darwin’s work — it was only later adapted into the theory of evolution. But it does a pretty good job of explaining the general concept.

For example, in giraffes a longer necks represents an evolutionary advantage as it allows them to reach more food. Over time, nature selects against short-neck giraffes who, by contrast, are hard pressed to get enough to eat. They produce less offspring, have less energy to defend against predators, and eventually disappear along with the genes for short necks.

Image credits Richter Maganhildi.

Image credits Richter Maganhildi.

But the phrase does leave some questions unanswered; for example, how much longer has one giraffe’s neck have to be compared to the others’ to count as “fitter” in the eyes of evolution?

Professor Diarmaid Hughes and graduate student Gerrit Brandis set out to measure just that, by studying bacterial genomes. The team observed Salmonella in their experiments, but the mechanisms they investigated (such as competition for food, or the selective pressure to use that food to grow faster than their peers) hold true for all organisms.

In order to grow, bacteria must translate their genetic code into amino acids and then assemble them into proteins. Growth is thus bottle-necked by the the speed of translation. Genetic information also has ‘redundancy’, meaning that there are several different pieces of code (codons) that can be translated into any one amino acid.

Brandis and Hughes wanted to know whether it mattered which particular codons were used to make EF-Tu, one of the most important proteins in Salmonella. They altered the genetic makeup of the bacteria and found that switching even a single codon in the gene for this protein with any one of the alternative codons reduced the organism’s fitness. On average, changing a codon reduced the speed of expression by 0.01 percent per generation.

But even this tiny amount was enough to determine a selective advantage, creating a codon usage bias — the widespread use of particular codons to make highly expressed proteins. This bias is seen in nearly all fast-growing organisms, such as bacteria and yeasts that cause infections in humans.

Over hundreds of millions of years, translation mechanisms were shaped by evolution to be as efficiently as possible — and in the adaptation race, even a hundredth of a percent counts.

The full paper, titled “The Selective Advantage of Synonymous Codon Usage Bias in Salmonella” has been published online in the journal PLoS Genetics and can be read here.

Key findings help unravel journey from inanimate chemistry to life

In the beginning, the Earth’s surface was a lifeless, hot, but chemically rich place. In these harsh conditions, the first amino acids synthesized from inorganic compounds, and from them, proteins formed. They built the first single cells, which went on to form plants and animals. Recent research helps us understand the process that created amino acids, and there is a widespread consensus in the scientific community as to the path cells took to evolve to complex life as we know it today. But there is a missing link in the chain of events that ties lifeless to life: how and why did amino acids form the proteins that underpin the functions of every cell?

University of North Carolina scientists Richard Wolfenden and Charles Carter have shed new light on how the building blocks came together to form life some 4 billion years ago.

“Our work shows that the close linkage between the physical properties of amino acids, the genetic code, and protein folding was likely essential from the beginning, long before large, sophisticated molecules arrived on the scene,” said Carter, professor of biochemistry and biophysics at the UNC School of Medicine. “This close interaction was likely the key factor in the evolution from building blocks to organisms.”

Their findings, published in companion papers in the Proceedings of the National Academy of Sciences, contravene the traditional yet problematic “RNA world” theory, which posits that RNA -implicated in various biological roles in coding, decoding, regulation, and expression of genes- came into existence from the primordial pool, created the first simple proteins, peptides, and thus led to the creation of the first cells; in fact, they argue, it’s just as likely that peptides catalyzed the creation of RNA as the polymeric molecule was to lead to the formation of these simple proteins.

A strand of RNA Image via: miltenyibiotec.com

A strand of RNA, the first records of genetic information.
Image via: miltenyibiotec.com

The scientific community places the last universal common ancestor of all life on Earth, dubbed LUCA, at about 3.6 billion years ago. LUCA was most likely a single-cell organism, had a few hundred genes which stored the blueprints for DNA replication, protein synthesis, and RNA transcriptions. It had the basic components that modern organisms have, such at lipids. In other words, it had all the traits we expect to find in complex life today. After LUCA, it’s relatively easy to see how modern life evolved. But there is little hard evidence of how LUCA came into being.

We know a lot about LUCA and we are beginning to learn about the chemistry that produced building blocks like amino acids, but between the two there is a desert of knowledge,” Carter said. “We haven’t even known how to explore it.”

Dr. Wolfenden’s and Dr. Carter’s research aims to bridge the knowledge gap. It creates a model where RNA did not have to just pop into existance, and shows how even before there were cells, it seems more likely that there were interactions between amino acids and nucleotides that led to the co-creation of proteins and RNA.

“Dr. Wolfenden established physical properties of the twenty amino acids, and we have found a link between those properties and the genetic code,” Carter said. “That link suggests to us that there was a second, earlier code that made possible the peptide-RNA interactions necessary to launch a selection process that we can envision creating the first life on Earth.”

In order to function properly, proteins must fold in certain ways. The first PNAS paper, led by Wolfenden, shows that both the polarities of the amino acids (how they arrange themselves between water and oil) and their sizes help explain the complex process of protein folding – how a chain of connected amino acids arranges itself to form a particular 3-dimensional structure that has a specific biological function.

“Our experiments show how the polarities of amino acids change consistently across a wide range of temperatures in ways that would not disrupt the basic relationships between genetic coding and protein folding,” said Wolfenden, Alumni Distinguished Professor of Biochemistry and Biophysics.

This is an important piece of information, as when life started to form, in early-Earth conditions, temperatures were much hotter than when the first plants and animals appeared. If amino acid interaction changed with temperature in such a way as to interfere with genetic coding, the system would have stopped working when the planet cooled down.  Life could not had evolved based on these principles.

A series of lab experiments with amino acids showed that two properties, namely size and polarity of amino acids, were necessary but also sufficient to explain how they behaved in folded proteins and that the relationship between the two held at the temperatures Earth had 4 billion years ago.

In their second PNAS paper, lead by Carter, they analyse how aminoacyl-tRNA synthetases recognized the enzymes that translate the genetic code, named transfer ribonucleic acid or tRNA. It shows that each one of the two ends of the L-shaped tRNA molecule has specific rules on what amino acid to tie to. The end that carried the amino-acid selects the molecule based on size. The other end, named an anticodon, selects it based on polarity:

“Think of tRNA as an adapter,” Carter said. “One end of the adapter carries a particular amino acid; the other end reads the genetic blueprint for that amino acid in messenger RNA. Each synthetase matches one of the twenty amino acids with its own adapter so that the genetic blueprint in messenger RNA faithfully makes the correct protein every time.”

“Translating the genetic code is the nexus connecting pre-biotic chemistry to biology”, he added.

Their findings imply that the relationships between tRNA and the sizes and polarities of amino acids were crucial during the Earth’s early days. And basing on Carter’s work with the active cores of tRNA synthetases, called Urzymes, it seems likely that selection by size preceded selection after polarity. Because of this ordered selection, the earliest proteins did not have to fold into unique shapes, which evolved later. This would help explain two paradoxes: how complex structures arose from simple conditions, and how biology divided the work between proteins and nucleic acids, two very different structures.

The structure of DNA, RNA, and proteins.
Image via: exploringorigins.org

“The fact that genetic coding developed in two successive stages — the first of which was relatively simple — may be one reason why life was able to emerge while the earth was still quite young,” Wolfenden noted.

“The collaboration between RNA and peptides was likely necessary for the spontaneous emergence of complexity,” Carter added. “In our view, it was a peptide-RNA world, not an RNA-only world.”

An earlier structure, that would enable coded peptides to bind RNA, would have provided a decisive selective advantage. This simple system would then undergo a natural selection process, paving the way for new and more biological forms of evolution.

 

 

 

 

Foam gushing off a pint - you either love it or hate it. Credit:

Magnets could help make less foamy beer

There isn’t a less dreaded sight in any respectable bar than a beer bottle gushing foam. It’s not the bartender’s fault though (not necessarily), since different assortments of beer have their signature foam – some make more, some make less. Breweries nowadays use all sorts of anti-foaming agents, and now food scientists in Belgium – the country with the most breweries per capita –  report a novel approach: using magnets.

Science for the greater beer

Foam gushing off a pint - you either love it or hate it. Credit:

Foam gushing off a pint – you either love it or hate it. Credit:

Foam doesn’t necessarily have to be a bad thing. Actually, the two-finger thick foam in a pint is seen a symbol and hallmark of good beer. Guinness, for instance, adds nitrogen to make the foam tastier. When beer foams, it is obviously due to the creation of bubbles. This phenomenon is referred to as nucleation, which is not that well understood. Basically, what happens is a group  of proteins and smaller polypeptides (additional proteins) act as a group and individually as foam positive agents. One particular protein naturally found in barley is Lipid Transfer Protein 1 (LTP1), and it plays a large role in a beer’s foam.

LPT1 is very hydrophobic – it doesn’t like water – so in order to make means, it latches on to CO2 bubles, which are produced during the fermentation process, as well as during the bottling. The protein piggybacks the CO2 and rises to the surface where it forms a coating on the bubbles maintaining the foam. When fungi infect the barley grains in beer’s malt base, these can cause the beer to overfoam. To counter this, brewers add hops extract, an antifoaming agent that binds to the hydrophobic proteins first.

Writing in the  Journal of Food EngineeringBelgian researchers report an ingenious way to reduce foam. They applied a magnetic field to a malt infused with hops extract to disperse the antifoaming agent into tinier particles. Imagine a big sphere and 1,000 other smaller spheres which when joined together form the big sphere. Which of the two has the greatest surface area? That’s the trick. It’s mostly used in chemical applications, especially when working with expensive catalysts like platinum. You break your agent into smaller parts so the surface area is greater, thus reacting more.

The team reports that the smaller particles were much more effective at binding to more hydrophobins, blocking carbon dioxide and decreasing gushing. When the technique was applied to a real brewery, much lower amounts of hops extract were needed to stop foaming. This translates into savings, making the findings of great interest for the beer industry. Future research is needed to determine whether the magnetic field alone is enough to reduce foaming at an industrial scale.