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How the cell's waste management systems might be targeted to treat cancer – The Conversation Indonesia

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Human organs and tissues are made up of millions of microscopic living units called cells. Over their lifespans, these cells accumulate waste products that include unwanted, misfolded and surplus proteins.

Waste management within these cells is a complex and critically important process that is essential for the proper functioning of organs within any given system.

The faulty functioning of cellular waste management machinery can lead to cancer and neurodegenerative diseases. As researchers in immunology and oncology at the Université de Montréal, we want to explain how this process allows cells to adapt to adverse situations.

Proteins are essential

Every cell, tissue or organ contains thousands of different genes. Like a barcode, the genetic information in our DNA is read and translated, enabling the production of thousands of different proteins. Each protein has a precise 3D structure, a specific location and role within a cell type.

Proteins are functional units, similar to tiny machines, that carry out many processes within cells. These processes include the uptake of nutrients to ensure cell survival, cell respiration using oxygen to promote energy production, cell proliferation to replace dead cells and promote organ growth, and cell migration within tissue to place them in the right place at the right time. In short, proteins are responsible for the proper functioning of all cellular processes and allow cells to coexist in harmony within an organism.

Each of our cells has exactly the same set of genes, but each cell type has a unique protein profile. For example, one type of protein may be present and active in brain cells but absent in kidney or muscle cells. A protein might be essential for one organ but not for another, and their presence or absence within the cell is governed by a dynamic balance, orchestrated by mechanisms that regulate protein production and elimination.

How cells decide which proteins to discard

Over the past few decades, researchers have learned a great deal about how proteins are produced from genes via messenger RNA translation. This process involves a structure called the ribosome, the factory for protein production.

Once produced, some proteins must be eliminated, either because of they are misfolded or because they have become redundant. Protein degradation is a highly co-ordinated and complex cellular process.

Balance between protein synthesis by the ribosome and degradation by the proteasome.
(El Bachir Affar, created on BioRender.com), Author provided

Our lab, among others, is interested in understanding how cells make the initial decision to eliminate proteins and then proceed to destroy them. To ensure their removal, cells set up a complex process of quality control and decision-making that results in protein ubiquitination. Ubiquitination is an essential process that consists of binding a small protein, called ubiquitin, to various unwanted protein targets. It occurs in all cells in the body.

The ubiquitination stamp allows the proteasome to recognize unwanted proteins and sort them for removal. The proteasome is a tiny cylindrical chamber made up of many specialized proteins, which act like molecular scissors to shred proteins. As an essential protein complex, there are multiple copies of the proteasome in all living cells.

The proteasome is responsible for the rapid and highly specific breakdown of unwanted, misfolded or surplus proteins. This process is extremely important for the proliferation and proper functioning of cells.

The aberrant or reduced degradation of cellular proteins can lead to a variety of diseases, including cancer and brain diseases. However, the exact mechanisms underlying the normal functions and pathological alterations associated with the proteasome are still poorly understood.

Cells react to lack of nutrients

We recently discovered that when the body is nutrient deprived, proteasomes assemble in the nucleus of cells to form large structures called “bodies” or “foci.” This aggregation of proteasomes can be observed in various cell types and is a general cellular response to nutrient deprivation.

Specifically, this phenomenon only occurs when cells are deprived of amino acids, the necessary building blocks of proteins. Consequently, there’s a tightly controlled balance between the supply of amino acids for protein synthesis and their break down by the proteasome.

The formation of proteasome foci amplifies this degradation process during periods of nutrient deprivation. Interestingly, our study also found that these foci promote cell death during severe nutrient stress, where the cell triggers molecular mechanisms that lead to its destruction, a form of cellular suicide. Although this cell death is detrimental to individual cells, the outcome could be beneficial for overall cell population that forms the tissues and organs.

In fact, the death of some cells in an organ, in response to nutrient deficiency, could initially decrease the competition between cells for limited resources. The release of cellular components, in particular nutrients, during cell death could help nearby cells survive. In addition, dying cells could send signals to summon specialized rescue cells to repair tissues.

We also found that some cells present in tumours have a reduced ability to form proteasome foci following nutrient deprivation, suggesting that these cells have acquired resistance to stress. The formation of these foci, in normal cells, could be a defence mechanism that promotes the death of cells that have undergone drastic changes caused by the absence of nutrients.

In this respect, inducing cellular suicide by forming proteasome foci in cells that have undergone changes that promote cancer development could be an interesting new approach to prevent cancer.

figure

Proteasome foci and their involvement in cell death.
(El Bachir Affar, created on BioRender.com), Author provided

Now that researchers have a better understanding of what affects proteasome function, they could target it for personalized cancer treatment, which requires the knowledge of all the molecular disruptors of cancer cells.

It is possible that cells that escaped death as a result of nutrient stress have nevertheless accumulated changes in their functioning that could make them vulnerable. We are currently working on this hypothesis.

Malik Affar co-authored this article and helped produce the graphics.

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An award-winning photographer tells you how to take pictures of the night sky – CBC.ca

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Dave Brosha is a professional photographer who, over the last 15 years, has taken highly stunning pictures of the Canadian wilderness.

It was when he was living in Yellowknife — before he pursued photography full time — that he first became interested in pointing his lens toward the skies.

“Yellowknife is known as one of the best areas on the planet for displays of the aurora borealis,” he said. “I found myself outside many, many nights under the stars.”

Since then Brosha has been short-listed multiple times for the Astronomy Photography of the Year Awards, and in 2010 he was the first runner-up in the category of land and space.

Now that he’s based in P.E.I., he splits his time between doing commercial assignments and teaching photography to people across Canada and in other parts of the world. 

Every summer, he holds a workshop on the Island with his colleague, Paul Zizka, on sunset and nighttime photography that features astrophotography, the art of capturing a picture of an object in space.

“Between Worlds.” Self-portrait photographed on the edge of a glacier in Iceland. ISO 3200, f/2.5, 30-seconds. (Dave Brosha/Dave Brosha Photography)

“There’s people that are more into deep-space photography, actually photographing the galaxies and close-ups of planets and stars and stuff like that,” Brosha said. “But to me, astrophotography is really just going out into the world once the light disappears and just exploring the beauty of that.”

Dave Brosha. (Amy Stackhouse)

Though his workshop just ended, Brosha took some time to tell CBC what beginners need to know to get into this hobby, which he says at its most barebones doesn’t require more than a fairly basic DSLR camera or a good smartphone — not even a fancy location.

“My favourite nighttime photographs have always just kind of come in my own backyard. I don’t have to drive anywhere, and it’s right there,” he said. 

“Whether exploring star trails or aurora borealis or Milky Way photographs, or just being able to go outside in your own backyard, it’s [all] pretty wonderful. 

“It helps to live in the countryside.”

Switching to manual

All good nighttime photographers — and all good photographers in general — must have a firm grasp on the concept of exposure. That’s the amount of light that’s allowed to reach the camera sensor. A picture that’s underexposed is one that looks too dark.

“Apparitions.” Photographed on a still night at low tide at Hopewell Rocks, New Brunswick. (Dave Brosha/Dave Brosha Photography)

“You have to understand the principles of capturing very small amounts of light over a longer time. So you have to know how to be able to operate your camera to capture those miniscule bits of light,” Brosha said. “It really forces you to slow down and think.”

For starters, that means ditching your camera’s auto settings. 

“You can’t really shoot night photography effectively in just auto mode. You have to learn the exposure triangle,” he said. “It takes a little bit of work, for sure. But the rewards are tremendous.”

Keep it steady

“World Goes Round”. The Old Man of Storr in the Isle of Skye, Scotland. ISO 4000, f/2.8, timelapse stitch of 45 30-second images. (Dave Brosha/Dave Brosha Photography)

The longer the camera’s shutter remains open, the larger the amount of light the camera takes in. As such, in a night photography environment, it’s common to see shutter speeds of over 20 to 30 seconds. 

But a slow shutter speed means the camera is very sensitive to any motion.

That’s great if you’re trying to capture the movement of celestial bodies such as when taking a “star trail” photograph, but even a slight movement could lead to blurry images.

Brosha said that for long exposures, it’s important to keep your camera steady. That means a good tripod is almost a must.

“If all else fails, I’ve improvised by propping my camera up on a solid surface,” Brosha said. “Using a timer on your camera rather than pressing your shutter also helps reduce camera shake.”

Check your ISO

Cranking up the ISO allows for more light to get in the camera at the expense of quality.

That could compensate for a faster shutter speed when capturing a moving object, such as when trying to capture the outlines of bright northern lights.

And having both a slow shutter speed and a high ISO could lead to highly detailed images of the night sky, such as this self-portrait with the Milky Way as a backdrop. It was taken with a 3200-ISO, and a 30-second shutter speed.

“Shine Your Light.” Self-portrait taken in The Pinnacles in Western Australia. ISO 3200, f/2.8, 30 seconds. (Dave Brosha/Dave Brosha Photography)

“When you go out there, and you even just let your eyes adjust for the dark, and you’re out there an hour, it’s remarkable how much more you see. The camera can take that even further,” Brosha said. “[It] picks up so much more.”

Perfect conditions

Brosha said that other than avoiding pouring rain, there are no real “ideal” conditions as to when to venture out, and that all types of weather can lead to interesting pictures.

“Cloudy? Reflected light pollution can actually look interesting in a long exposure. Full moon? Not the best conditions for shooting the Milky Way, but great conditions for being able to see your foregrounds,” he said.

“Where The Wild Winds Blow.” Portrait of Maggie Hood, Iceland. ISO 3200, f/2.2, 2.5-seconds. The subject was lit by an off-camera strobe. (Dave Brosha/Dave Brosha Photography)

A pitch-black night is a prime setting for taking pictures of stars. And if you’re looking to take a picture of the northern lights, you better look, well, north.

“It’s generally easier to photograph on the North Shore, when the aurora borealis is predicted. So that’s what I would probably recommend to people,” Brosha said.

Go out there and shoot

“Night Falls.” Alexandra Falls in the Northwest Territories. ISO 1600, f/7.1, 25-second exposure. (Dave Brosha/Dave Brosha Photography)

Brosha said that astrophotography may look intimidating on the surface, but that it’s not as complicated as most people might think. 

“All you have to grasp to begin is the concept of long exposure. And that usually I find for people is something that they can get the hang of pretty quickly. It just takes a little bit of practice,” he said.

Once you got that nailed down, Brosha said you can get really creative with it. And the setting allows for that.

“Every time you turn on a light, like a flashlight, your eyes kind of lose the adjustment to the nighttime that you’ve gained,” he said. 

“So you really try to function with as little light as possible. And so everything becomes slower and more deliberate.”

Plus, Brosha said, it’s a fine excuse to go outdoors.

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It's once again time for the Perseids, one of the best meteor showers of the year – CBC News

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Each August, Earth plows through a thick trail of debris left over from a passing comet. The result: A spectacular night of meteors lighting up the sky.

One of the best and most anticipated meteor showers of the year is the Perseids, which takes place from mid-July to the end of August. But peak viewing — where you’ll get a chance to see the most meteors — falls on the night of Aug. 12-13 this year, according to the International Meteor Organization. 

That’s when Earth moves through the thickest part of the debris left over from comet 109P/Swift-Tuttle, with tiny pieces of particles burning up in our atmosphere at 59 km/s.

Try this interactive map showing how Earth passes through the meteor shower:

Swift-Tuttle, which was first discovered in 1862 independently by both Lewis Swift and Horace Tuttle, makes an orbit of the sun every 133 years. The last time it was in our solar system was in 1992. Still, from all those trips around the sun, it’s left behind plenty of debris. 

Some of this debris can be bigger than the normal grain-like particles and can create beautiful bolides, or bright fireballs that light up the sky.

How to see the meteors

Though the Perseids rarely disappoint, there is one thing to contend with this year that may hamper your viewing delight: the full moon.

With the moon lighting up the sky, that means that only the brightest of meteors will be visible. Fortunately, many Perseids tend to be quite bright anyway. 

The Perseids are given their name for the constellation — Perseus. This is the point in the sky from which they seem to appear, called the radiant.

This map shows the radiant of the Perseids, which get their name name from the nearby constellation Perseus. The radiant is the point in the sky from which the meteors seem to appear. (American Meteor Society)

While some people like to look in the direction of the constellation, which rises in the northeast, it limits the number of meteors that can be seen, since they will have shorter tails. To see longer meteors (ie., with long tails), you don’t need to look directly up, but at more of an angle.

And the best thing about meteor showers is that you don’t need a telescope or binoculars, just your own eyes.

You can also keep an eye out for “earthgrazers,” meteors that skim Earth’s atmosphere and, as a result, leave a long trail behind them.

These are best viewed early in the night, when the sky is dark and the radiant is low in the east. They will be moving roughly from north to south.

To increase your chances of catching some bright meteors, you could head out ahead of the peak night of Aug. 12, or even in the days after, when the moon won’t be entirely full. Try to keep the moon behind you when stargazing to block out its glare. 

Helpful hints

Another hot tip is to try to lie down on a blanket or even on a beach lounge chair, otherwise your neck will get tired and ache from trying to look up. 

Also, put away those phones as your eyes will need to become accustomed to the dark, something that can take anywhere from 30 minutes to an hour. And remember, the more stars you can see, the more faint meteors you will catch, so try to get to as dark a location as you can, away from city lights.

Patience is your friend, so try not to give up if you haven’t seen any meteors within a few minutes. Under ideal conditions, the Perseids can produce more than 100 meteors an hour, but don’t expect to see that many. 

At this time of year, you can also catch a couple of planets: Jupiter will be low in the east and hard to miss, and Saturn will lie in the southeast.

People can also use free apps like StarWalk or SkyView (they have a night mode that displays in red in order to preserve your night vision) that allow you to hold your phone up to the sky to identify constellations, planets and more.

There’s always something to look at in the night sky, even if meteors aren’t providing a show.

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Watch OSIRIS-REx's Complex Orbital Path Around Bennu in This Cool Animation – Universe Today

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The OSIRIS-REx spacecraft conducted a two-year reconnaissance and sample collection at the asteroid Bennu, providing crucial data about the 500-meter-wide potentially hazardous rubble pile/space rock. When OSIRIS-REx arrived on Dec. 3, 2018, it needed some tricky navigation and precise maneuvers to make the mission work.

Experts at NASA Goddard’s Scientific Visualization Studio created an amazing visualization of the path the spacecraft took during its investigations. A short film called “A Web Around Asteroid Bennu” highlights the complexity of the mission, and the film is being shown at the SIGGRAPH computer graphics conference in Vancouver, British Columbia, Canada, a festival honoring standout works of computer animated storytelling.

Other films in the festival include Disney’s “Encanto” and Warner Brothers’ “The Batman.”

[embedded content]

Data visualizer Kel Elkins compiled the data for the film, which shows the web-like flight path for OSIRIS-REx, as well as the touch-and-go, or TAG, maneuver to collect the sample from the asteroid’s surface.

“I started working with the trajectory data in 2015,” Elkins said. “And when you first see an image of all the different maneuvers it looks like a rat’s nest. But it was really exciting to see these complicated maneuvers in 3D space.”

The video runs about four minutes in total, showing the flight path around Bennu from beginning to end in a single, continuous shot.

Screenshot from the visualization of OSIRIS-REx’s orbital path.

“From a trajectory and navigation perspective, the team really did things that have never been done before in planetary exploration,” said Mike Moreau, deputy project manager for OSIRIS-REx at NASA Goddard. “We flew the spacecraft closer to this object than any spacecraft has ever been flown before; we did maneuvers that were centimeters per second, or millimeters per second, in order to get the spacecraft exactly where it needed to be and to change its orbit.”

Taking their data visualization to the next level, Elkins and colleagues plan to release a 360-degree version of “A Web Around Asteroid Bennu” that wraps the video around the viewer, for an interactive experience on VR headsets, mobile devices, and online.

“As amazing as it is to see the trajectory in front of you in the original format, there’s something about putting the viewer in the middle of it and letting them look around,” Elkins said. “You’re in space and OSIRIS-REx is flying around you. We’re really excited to be able to publish this additional 360-degree view.”

This illustration shows the OSIRIS-REx spacecraft departing asteroid Bennu to begin its two-year journey back to Earth. Credits: NASA/Goddard/University of Arizona

OSIRIS-REx is currently on its way back towards Earth, and in September 2023, will drop off a sample in the Utah desert. Once the sample is retrieved, the spacecraft has been given a new mission, and it will be heading to one of the most infamous asteroids of them all, the potentially hazardous asteroid Apophis for an 18 month study. The mission will be renamed OSIRIS-APEX, which is short for OSIRIS-Apophis Explorer.

Source: NASA

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