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Can Gene Editing Cure Prion Diseases? | Insights from Cyworthy

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DNA molecules are essential carriers of genetic information, including partner molecules. RNA encodes the building blocks of life, specifically amino acids. Together, DNA, RNA, and amino acids form larger structures known as genes, which make up the genetic code for proteins that perform vital functions or contribute to other significant biomolecules.

Occasionally, the RNA within a gene may contain defects that can severely impact protein functionality. Such misfolded proteins, which can lead to fatal diseases, are known as prions. Researchers are optimistic that advancements in RNA editing technology, such as CRISPR, could provide treatment for prion diseases.

The possibility of this treatment has been known since scientists first identified bacteria using natural gene editing methods to combat viruses. Recently, medical researchers from institutions such as Harvard University, the Massachusetts Institute of Technology, and Case Western University conducted a pilot study to explore CRISPR’s effectiveness against prion diseases. The research team aimed to identify defective RNA regions within the genome and modify the corresponding genes. This process involved pinpointing the start and stop codons crucial for gene expression.

In laboratory experiments, scientists collected RNA from mice infected with human prion diseases. Utilizing CRISPR technology, they modified the defective RNA at the molecular level by inserting new start and stop codons to prevent replication. They employed sgRNA designed to produce non-functional proteins. Three versions of the sgRNA were tested: sgRNA, F-sgRNA, and F+E-sgRNA.

The researchers administered a medically approved vector, specifically an adeno-associated virus loaded with modified sgRNA, into mice infected with prion disease. They hypothesized that successful intervention would halt prion replication and prevent related disorders.

To evaluate this, scientists used two groups of mice, one experimental group receiving the modified sgRNAs and a control group receiving none. At ages 6 to 9 weeks, both groups were injected with various strains of human prion disease. Subsequently, only the experimental group was treated with sgRNA between 7 to 10 weeks old.

The mice were monitored for 92 to 95 weeks, recording behavioral changes, weight fluctuation, and lifespan. Post-experiment, researchers compared the health outcomes of both groups to determine the efficacy of the treatment. The findings were promising: treated mice exhibited nearly a 60% increase in lifespan compared to their control counterparts.

To assess the experiment’s success, researchers euthanized the mice post-study and analyzed their brains. They were particularly concerned with ensuring that the edited RNA targeted the proper genes, avoiding off-target editing that could lead to unpredictable outcomes. A thorough examination for possible side effects and abnormalities not linked to prion activity was conducted.

Additionally, they assessed the prion activity to confirm the impact of CRISPR on the targeted RNA strand, focusing on prion protein levels in mice. They observed that treated mice had prion protein levels 4% to 40% lower than those in the control group, with the F+E-sgRNA treatment yielding a 43% reduction in prion levels.

The research team concluded that CRISPR gene editing holds potential for combating prion diseases in mice. However, the significant off-target editing observed could present risks in human applications due to possible adverse effects. The researchers recommend future investigations continue using rodent models until more precise editing techniques are developed. Nevertheless, these results symbolize a meaningful advance toward potential treatments for prion ailments in humans.

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Source: sciworthy.com

How Did Mars Acquire Its Moons? – Cyworthy

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The moon of Earth stands out as a prominent feature in our night sky. Scientists largely agree that during the early stages of Earth’s formation, a smaller, planet-like object collided with Earth, ejecting a substantial amount of material into space. This debris was subsequently pulled into orbit around Earth due to gravity and maintained a slow enough speed to become trapped in Earth’s gravitational field. However, the
giant impact hypothesis
has provided clarity on the origin of our moon. In contrast, the origins of other moons in our solar system, like the Martian moons Phobos and Deimos, remain a topic of debate.

An alternate theory suggests that two small celestial bodies approached Mars early in its existence and collided with the gas and dust clouds left from its formation. This surrounding dust could have decelerated them sufficiently for Mars’ gravity to capture them. This theory is referred to as the
gas drag capture hypothesis
and may account for the existence of Phobos and Deimos. Furthermore, they are composed of
different materials
than those found on Mars
, which raises additional questions.

One challenge to this theory is that the dust density around Mars would have to be several times greater than current models of solar system formation indicate, to slow down approaching objects effectively. Additionally, there’s a question of probability. Although Phobos and Deimos both have orbits that lie within 2° of the Martian equator, the odds of both objects aligning with Mars at an angle that matches the equator is around only 0.00001%.

To investigate the viability of this scenario, two scientists from Japan developed a model aimed at calculating the trajectory of a Phobos-sized object approaching Mars. The aim was to show, through various challenges, that the gas drag trap hypothesis might not be as implausible as previously believed.

Phobos orbits Mars about 3,700 miles or 6,000 kilometers above the planet’s surface and is slowly falling towards Mars. Deimos orbits Mars at a distance of 14,600 miles, or 23,500 kilometers. “Mars Moons” by Muskid is licensed under CC BY-SA 3.0.

Initially, the researchers defined the pertinent equations of motion to include in their model. This included variables such as the angular velocity of an object approaching Mars, its distance from the planet, its potential energy, and the drag force that reduces its speed. Additionally, they factored in Mars’ mass and the state of the surrounding matter at the time, which they referred to as the primitive atmosphere of Mars. They estimated this atmosphere’s temperature at 200 Kelvin (approximately -73°C or -100°F) and its density at 4.7 × 10.-7 kilograms per cubic meter, increasing near the Martian surface and decreasing exponentially with height.

Next, the team needed to establish the initial orbit of the incoming satellite, testing eight different speeds ranging from 20 meters/second to 160 meters/second (about 45 miles/hour to 360 miles/hour) in 20 meters/second increments. There were 4,096 angles of incidence to be tested relative to Mars’ equator and poles, leading to a total of 32,768 initial trajectory combinations for objects approaching Mars.

Their findings indicated three potential outcomes for objects entering Mars’ primordial atmosphere: they could escape Mars’ gravitational grasp, become temporarily trapped, or be permanently ensnared. Remarkably, nearly all objects approached at the slowest speeds were captured in some capacity, while only around 10% of those at the highest speeds were captured. The researchers posited that about 1 in 50 incoming objects would be permanently secured by Mars, particularly if they lost enough energy, limiting their orbits to within 10 degrees of Mars’ equator.

The research team proposed a potential history for Phobos and Deimos, suggesting that due to their composition, they likely formed in the outer solar system, possibly within or beyond the asteroid belt. Over time, they may have been scattered by Jupiter’s gravitational influence, gradually approaching Mars at the right angles and speeds to be captured by its gas, resulting in their current eccentric orbits. Eventually, their orbits became slower, more circular, and moved closer to Mars.

This proposed scenario aligns well with current observations of Phobos and Deimos. The research team anticipates that future
Mars satellite exploration
missions will further investigate these moons. The planned mission will orbit Mars and then Phobos, conducting detailed observations and remote sensing while collecting surface samples to return to Earth, enhancing our understanding of these moons’ origins. The mission is set to launch in 2026, with Phobos samples expected to arrive back on Earth in 2031.


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Source: sciworthy.com

How Did the First Galaxies Come to Be? – Cyworthy

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Light travels at a finite speed, meaning it takes time to cover vast distances. Astronomers leverage this to investigate ancient epochs in the universe’s history by examining distant celestial objects. Due to inherent geometric and physical constraints, objects become smaller and dimmer the farther away they are. Additionally, when trying to focus a telescope on a small, faint, and distant target, your view might be obstructed by something larger, closer, and more luminous.

In certain scenarios, scientists can circumvent this limitation and even turn it into an advantage. Like matter, light is influenced by gravity; its trajectory curves as it passes through a gravitational field. The larger an object, the stronger its gravitational pull, resulting in more pronounced bending of light.

When confronted by a massive entity like a galaxy cluster, the light from objects positioned behind it is significantly bent, leading to distorted and magnified images, akin to passing through a lens. This effect, where a distant object appears enlarged due to the gravity of a nearby massive object, is known as gravity lensing.

A group of astronomers recently studied an ancient galaxy, A1689-zD1, which is gravitationally lensed by the galaxy cluster Abel 1689. A1689-zD1 is currently about 25 billion light-years away from us, equivalent to 150 sextillion miles or 240 sextillion kilometers. The light we observe from it has traveled for approximately 13 billion years, around the same duration as the universe’s 14 billion-year lifespan.

By analyzing this light, astronomers can explore the characteristics of galaxies as they were 13 billion years ago. They hypothesize that galaxies at this distance are in the initial phases of their formation and evolution, a period they refer to as the dawn of the universe. Investigating galaxies from this era provides astronomers with valuable insights into the formation processes of galaxies.

To conduct their observations, the team gathered data from multiple sources, including a radio telescope situated in the Atacama Desert in Chile. They utilized the Atacama Large Millimeter/Submillimeter Array (ALMA) to analyze light emitted by oxygen and carbon ions in galaxies. They also employed the Green Bank Observatory VEGAS spectrometer, which searches for light emitted by carbon monoxide molecules in galaxies. The radiation from these ions and molecules aids astronomers in determining a galaxy’s structure and examining the motion and interaction of its various components. Finally, the team integrated archival images from A1689-zD1 from the Hubble Space Telescope and the Spitzer Space Telescope to create a composite image in ultraviolet and infrared light, allowing for comparison with their radio data.

While gravitational lenses are beneficial to astronomers by revealing hidden light sources and enhancing them, they often produce distorted representations of objects. To ascertain the galaxy’s true shape, the research team needed to account for these distortions, utilizing Abel 1689’s model of light’s gravitational bending effect. By employing the software Lenstool, the research team accurately characterized the dynamics of A1689-zD1 to within less than 1% of the Milky Way’s width, measuring 200 parsecs, or around 4 quintillion miles and 6 quintillion kilometers.

The team discovered that A1689-zD1 is substantially larger than what a previous study estimated, which suggested a mass between 2 to 4 billion times that of the Sun. The new findings indicate its total mass to be around 20 billion times that of the Sun. They also observed that this mass is divided into five distinct regions, each exhibiting different movements and locations. Moreover, these parts displayed no indications of forming a single rotating disk, unlike the familiar spirals of the Milky Way.

The researchers proposed three potential explanations for this observation. One possibility is that these regions represent components of a single extended galaxy, existing as large molecular clouds or star-forming clusters. Another conjecture is that A1689-zD1 resulted from the merger of at least two smaller galaxies, with the differing regions emerging from the collision and gravitational interactions of the merging galaxies. Lastly, they suggested that the first two hypotheses may not be mutually exclusive, but current data does not allow for determining the extent of either occurrence.

The researchers noted that much of this uncertainty could be clarified through follow-up investigations using the James Webb Space Telescope (JWST). They also highlighted that considerable aspects of A1689-zD1 remain obscured in the studied wavelength range, contributing to the ongoing discrepancy between mass estimates derived from starlight counting and those determined by analyzing stellar motion. Overall, they concluded that their findings suggest galaxies in the universe’s infancy present a diverse and intricate nature.


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Can Cells Form in Venus’s Clouds? – Cyworthy

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Venus, the second planet from the Sun, is often called Earth’s sister planet. If extraterrestrial observers on a remote exoplanet were to analyze our solar system with the same methods used by observers on Earth today, the two planets would appear strikingly similar. Both are rocky, with nearly identical diameters and masses, and both exist within or near the solar system’s habitable zone. However, only one of them is known to support life.

A significant difference between the two planets—and a likely reason for the first—is their atmospheric compositions. Earth’s atmosphere comprises approximately 78% nitrogen and 21% oxygen, whereas Venus’ atmosphere consists of more than 96% carbon dioxide. In the distant past, volcanic activity released this carbon dioxide, triggering an uncontrollable greenhouse effect. This process, coupled with Venus’ proximity to the Sun, has driven its surface temperature to a searing 500°C (900°F).

Harold Morowitz and Carl Sagan first observed in 1967 that although Venus’ barren surfaces may be inhospitable to life as we know it, its clouds present “an entirely different story,” according to Morowitz. The upper atmosphere of Venus contains low levels of water vapor and cloud regions characterized by extreme temperatures and pressures. These conditions could potentially support some types of terrestrial microorganisms and have led scientists to investigate the clouds of Venus. In the 1970s, these clouds were found to be primarily composed of sulfuric acid, which is considered incompatible with life. Nevertheless, a controversial detection of phosphine—gases found in Venus’ clouds that could be produced by microbes on Earth—has prompted some astrobiologists to reevaluate this notion of habitability. This has opened discussions on potential habitability.

Previously, researchers established that biomolecules such as the nucleic acids forming DNA can remain stable for up to one year in sulfuric acid concentrations ranging from 81% to 98%. To advance this research, scientists at the University of Chicago have recently tested whether more complex organic structures can also form in concentrated sulfuric acid.

They began with a set of carbon-based molecules known as lipids. Lipids serve as the foundation of cell membranes, acting as a barrier to the external environment and regulating what enters and exits the cell. The research team contended that cell membranes are essential for life, especially under extreme conditions like those present in Venus’ clouds. Thus, they evaluated whether simple lipids could create membranous structures called vesicles in concentrated sulfuric acid.

Membrane lipids feature one side that is attracted to water, known as the hydrophilic side, and another that repels water, termed the hydrophobic side (Figure below, left). The hydrophilic side consists of long carbon chains, referred to as tails, while the hydrophobic side comprises charged compounds known as polar heads. In cell membranes, lipids are arranged in bilayers, with hydrophilic tails oriented inwards and hydrophobic heads facing outwards (Figure below, right). The research team selected simple, commercially available lipids with tails of 10 or 18 carbon atoms and polar heads of trimethylamine, sulfate, and phosphonate. These tailed lipids were chosen for their solubility and ability to form membrane structures due to their hydrophobic nature.

Illustration of a single simple lipid (left) and stacked lipids forming a cell membrane structure (right). Created by the author.

To assess the lipids’ resilience against sulfuric acid, various concentrations of each 10-carbon lipid were incubated in 1%, 30%, and 70% sulfuric acid for a minimum of 1 hour at room temperature. Utilizing a method that evaluates molecular structures based on their magnetic properties, they examined how increasing acid concentrations affected the lipids. Results indicated that trimethylamine and phosphonate lipids remained stable in up to 70% sulfuric acid, although around 20% of the sulfate head degraded.

The researchers then explored whether the lipids could form vesicles in these sulfuric acid solutions. They prepared lipid mixtures across varying concentrations in 70% to 90% sulfuric acid, measuring the particle size of the lipid-acid mixture using light scattering techniques. They discovered that a 50/50 blend of 10-carbon or 18-carbon lipids produced particles comparable in size to typical vesicles in 70% and 80% sulfuric acid solutions, with these particles maintaining stability even after a week.

Upon examination under a high-powered microscope, the lipid particles formed foam-like vesicles. Lastly, numerical models illustrated that the charged ends of lipid and acid molecules interact at the molecular level to help stabilize the vesicles and prevent the entry of acid.

The researchers concluded that simple lipids can create stable membrane-like structures in sulfuric acid concentrations similar to those found in Venusian clouds. They recommended that future studies conduct laboratory experiments to validate the molecular model and ascertain whether lipid membranes can effectively block sulfuric acid. These scientists are beginning to formulate a clearer picture of the potential types of life that could exist within the cloud layers of Venus, although that picture remains largely incomplete.


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Source: sciworthy.com