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Category: chemistry – Page 68

Blebbisomes are large, organelle-rich extracellular vesicles with cell-like properties

Super cool paper where Jeppesen et al. discover and characterize a new type of large extracellular vesicle (EV) that they call blebbisomes! These blebbisomes have active mitochondria as well as other organelles (except nucleus), secrete and take up smaller EVs, and can reach sizes of up to 20 micrometers! #cellbiology #molecularbiology #biochemistry

Cells release a variety of 30-to 10,000-nm lipid-bilayer-enclosed extracellular vesicles (EVs) to facilitate cell-to-cell and cell-to-environment communication by packaging signalling molecules to avoid degradation1,2,3,4,5 and escape immune surveillance6,7,8,9. EVs may interact with target cells through contact between molecules on the EV surface with receptors on the cell surface to relay signals. In addition, modulation of recipient cell behavior may follow uptake of EVs cargo, including bioactive proteins, lipids and nucleic acids. EVs have emerged as important actors and agents of intercellular communication in normal cell biology and pathological conditions2,4,6.

Here, we identify blebbisomes, an exceptionally large functional EVs, that are actively released by human and mouse cells, remain motile independently of cells and have the capacity to both take up EVs and secrete exosomes and microvesicles. Blebbisomes are the largest type of EV described so far with an average diameter of 10 µm but can be as large as 20 µm, with an area commonly larger than 50 µm2. After being released from motile cells, blebbisomes display marked contractility-dependent ‘blebbing’ behaviour. Both normal and cancer cells release blebbisomes that contain active, healthy, mitochondria further distinguishing them from other large EVs (lEVs) such as exophers10,11 and migrasomes12 that function in the removal of damaged mitochondria from cells under stress conditions. In addition, blebbisomes contain many other cellular organelles including endoplasmic reticulum (ER), Golgi apparatus, ribosomes, lysosomes, endosomes, multivesicular endosomes (MVEs) and autophagosomes/amphisomes, as well as cytoskeletal elements; however, they lack a definable nucleus.

Scientists invent new drug candidates to treat antibiotic-resistant bacteria

There’s an arms race in medicine—scientists design drugs to treat lethal bacterial infections, but bacteria can evolve defenses to those drugs, sending the researchers back to square one. In an article published in the Journal of the American Chemical Society, a University of California, Irvine-led team describes the development of a drug candidate that can stop bacteria before they have a chance to cause harm.

“The issue with antibiotics is this crisis of antibiotic resistance,” said Sophia Padilla, a Ph.D. candidate in chemistry and lead author of the new study. “When it comes to antibiotics, can evolve defenses against them—they’re becoming stronger and always getting better at protecting themselves.”

About 35,000 people in the U.S. die each year from from pathogens like Staphylococcus, while about 2.8 million people suffer from bacteria-related illnesses.

What’s the future of connecting our tech to our brains?

A brain’s 86 billion neurons are always chattering along with tiny electrical and chemical signals. But how can we get inside the brain to study the fine details? Can we eavesdrop on cells using other cells? What is the future of communication between brains? Join Eagleman with special guest Max Hodak, founder of Science Corp, a company pioneering stunning new methods in brain computer interfaces.

A concise enzyme cascade enables the manufacture of natural and halogenated protoberberine alkaloids

Plant-derived alkaloids are an important class of natural products with various pharmacological properties1,2,3,4, including Rotundine (L-tetrahydropalmatine), berberine, morphine, colchicine, galanthamine and hyoscyamine (Fig. 1a). Many of them have been used as traditional medicines in China, Native America, India and the Islamic region. For instance, Rotundine was first isolated from Corydalis5, a plant that has been used as traditional Chinese herbal medicine for over a thousand years, known for its analgesic, anti-inflammatory, neuroprotective, anti-addictive, and antitumor activities6,7,8. Today, it also serves as an alternative to anxiolytic and sedative drugs from the addictive benzodiazepine group, as well as analgesics9. However, similar to many plant-derived natural products10,11, the commercial use of plant-derived alkaloids still mainly relies on extraction from medicinal plants with low abundance12,13,14,15, which is further affected by climate change, cultivation methods and location. Moreover, due to the lack of appropriate functional groups, derivatization of naturally occurring alkaloids to increase structural complexity and diversity through chemical methods remains challenging, restricting further drug development. Although chemical synthesis methods have been developed to overcome these issues, they often involve harsh conditions and heavy-metal catalysts16,17. In addition, the structural complexity of alkaloids, with their chiral centers and regioselective modifications, often results in low yields.

With the elucidation of the biosynthetic pathways of alkaloids and advancements in synthetic biology18,19,20,21,22,23,24,25,26,27, many efforts have been made to biosynthesize natural and unnatural alkaloids in microorganisms, including Saccharomyces cerevisiae and Escherichia coli28,29,30,31,32,33,34,35 (Fig. 1b). However, challenges such as the complexity of their biosynthetic pathways, the difficulties in expressing plant-derived P450 enzyme36,37,38 and berberine bridge enzyme (BBE)29,34,39,40, and the cytotoxicity from the accumulation of alkaloids or its intermediates34,41 always results in low production titers28,29,34, such as 16.9 mg L-1 production in berberine and 68.6 mg L-1 production in Rotundine in engineered yeasts, which still lack commercial viability. In fact, this remains a common manufacturing challenge for the heterologous biosynthesis of many plant-derived alkaloids in microorganisms.

Recently, it was reported that a designed nine-enzyme catalytic cascade enabled the efficient biosynthesis of the HIV drug islatravir42, and therapeutic oligonucleotides could be produced through an enzyme cascade in a single operation43. These seminal examples suggest that the designed enzyme cascades will revolutionize drug synthesis and development. Furthermore, specific enzymes can control the stereo-and chemoselectivity of chiral compounds44,45. Importantly, the use of modular “plug-and-play” strategy allows the easy incorporation or removal of enzymes to tailor the cascade for synthesizing different target compounds46,47, thereby introducing structural complexity and diversity. As for plant-derived natural products, steps catalyzed by enzymes that are difficult to express in engineered cells or that are still not identified can be bypassed through the careful selection of substrates46, making the process more efficient or feasible.

Solving the case of the missing platinum

For nearly two decades, scientists have been puzzled by the corrosion of negatively polarized platinum electrodes, a costly issue for water electrolyzers used in hydrogen production and electrochemical sensors.

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Now, researchers at the Department of Energy’s SLAC National Accelerator Laboratory and Leiden University have identified the culprit, paving the way for cheaper hydrogen energy and more reliable sensors.

Magnetic ‘invisibility cloak’ hides obstacles within particle streams

Researchers at the University of Bayreuth have developed a method that makes objects on a magnetic field invisible within a particle stream. Until now, this so-called cloaking had only been studied for waves such as light or sound. They report their results in Nature Communications.

Making objects invisible is no longer a purely fictional idea from fantasy or sci-fi films. At least to some extent, cloaking also works in research: manipulating objects in such a way that they become invisible to certain waves such as light or sound.

The Bayreuth researchers are extending cloaking to particle motions. Cloaking for particle streams on miniaturized chemical laboratories, so-called lab-on-a-chip devices, can help to transport active ingredients in a targeted manner without exposing them to undesirable premature chemical reactions.

Online test-time adaptation for better generalization of interatomic potentials to out-of-distribution data

Molecular Dynamics (MD) simulation serves as a crucial technique across various disciplines including biology, chemistry, and material science1,2,3,4. MD simulations are typically based on interatomic potential functions that characterize the potential energy surface of the system, with atomic forces derived as the negative gradients of the potential energies. Subsequently, Newton’s laws of motion are applied to simulate the dynamic trajectories of the atoms. In ab initio MD simulations5, the energies and forces are accurately determined by solving the equations in quantum mechanics. However, the computational demands of ab initio MD limit its practicality in many scenarios. By learning from ab initio calculations, machine learning interatomic potentials (MLIPs) have been developed to achieve much more efficient MD simulations with ab initio-level accuracy6,7,8.

Despite their successes, the crucial challenge of implementing MLIPs is the distribution shift between training and test data. When using MLIPs for MD simulations, the data for inference are atomic structures that are continuously generated during simulations based on the predicted forces, and the training set should encompass a wide range of atomic structures to guarantee the accuracy of predictions. However, in fields such as phaseion9,10, catalysis11,12, and crystal growth13,14, the configurational space that needs to be explored is highly complex. This complexity makes it challenging to sample sufficient data for training and easy to make a potential that is not smooth enough to extrapolate to every relevant point. Consequently, a distribution shift between training and test datasets often occurs, which causes the degradation of test performance and leads to the emergence of unrealistic atomic structures, and finally the MD simulations collapse15.

Taming terahertz: MIT’s new chip design breaks through silicon barriers

Additionally, their ability to penetrate various materials without harmful radiation makes them valuable for security screening, quality control in industries, and chemical sensing. However, until now, it has been challenging to harness the potential of these waves in electronic devices due to several technological limitations.

Finally, a new study from researchers at MIT reveals a chip-based solution that can overcome these limitations and make terahertz waves more accessible than ever.

Terahertz (THz) waves are affected by the dielectric constant, a measure of how well a material can store and slow down an electric field. The lower this constant is the smoother terahertz waves can pass through a material.

Holograms Take 3D Printing to the Next Level — With Amazing Precision and Speed

Traditional 3D printing builds objects layer by layer, but tomographic volumetric additive manufacturing (TVAM) takes a different approach. It uses laser light to illuminate a rotating vial of resin, solidifying material only where the accumulated energy surpasses a specific threshold. A key advantage of TVAM is its speed—it can produce objects in seconds, whereas conventional layer-based 3D printing takes about 10 minutes. However, its efficiency is a major drawback, as only about 1% of the projected light contributes to forming the intended shape.

Researchers from EPFL’s Laboratory of Applied Photonic Devices, led by Professor Christophe Moser, and the SDU Centre for Photonics Engineering, led by Professor Jesper Glückstad, have developed a more efficient TVAM technique, as reported in Nature Communications

<em> Nature Communications </em> is an open-access, peer-reviewed journal that publishes high-quality research from all areas of the natural sciences, including physics, chemistry, Earth sciences, and biology. The journal is part of the Nature Publishing Group and was launched in 2010. “Nature Communications” aims to facilitate the rapid dissemination of important research findings and to foster multidisciplinary collaboration and communication among scientists.

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