Beautifully executed paper on putting mechanoluminescent nanoparticles into blood circulation of mice which express optogenetic channels. Focused ultrasound can then trigger targeted light emission and control of neural activity in the brain and elsewhere.
A deep-tissue light source made from mechanoluminescent transducers stimulated by focused ultrasound enables wide imaging of live animal vasculature, and modulation of neuronal activity and behaviour.
Loss of an enzyme necessary for a process called lipoylation disrupts the way cancer cells copy their DNA, increasing their vulnerability to a class of anticancer drugs known as PARP inhibitors, a study led by UT Southwestern Medical Center researchers shows.
The findings, published in Science Advances, reveal a previously unrecognized mechanism to protect DNA replication and genome stability that could lead to new treatments for some cancers.
“This study shows that metabolism doesn’t just fuel cancer cells—it also directly shapes how DNA is copied and protected. This helps explain why inhibiting lipoylation could make tumors especially sensitive to PARP inhibitors,” said Yuanyuan “Faith” Zhang, M.D., Ph.D., Assistant Professor of Radiation Oncology and a member of the Experimental Therapeutics Research Program in the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. Dr. Zhang co-led the study with first author Zengfu Shang, Ph.D., Assistant Professor of Radiation Oncology in the Zhang Lab.
Researchers at the Champalimaud Foundation in Lisbon have for the first time managed to identify with an imaging technique whether nervous impulses in the brain of rats are flowing in a “bottom-up” (feedforward), carrying information about visual input, or a “top-down” (feedback) direction, carrying information about expectations or predictions on a given task or about the perception of the world around us. Their results, published in Nature Communications, could have important implications for understanding changes in the brains of people with hallucinations, Alzheimer’s, schizophrenia, autism, and other conditions.
Joana Carvalho, first author of the new study, who at the time was working in the Preclinical MRI lab led by senior author Noam Shemesh (she has since become a group leader at Coimbra University), “came up with the ideas, did the experiments and analyzed the results. I just brought the MRI expertise,” says Shemesh good-humoredly. Co-author Koen V. Haak from Tilburg University (Netherlands) gave assistance with the computational models and the others helped with the experiments.
The team showed that spontaneous feedforward and feedback nervous impulses in these rodents (the brain never sleeps) each have a unique, distinct signature, which can be detected by using a method they developed, called uFLARE (UltraFast Layer-Resolved Encoding), a neuroimaging technique designed to map brain activity with unprecedented high temporal and spatial resolutions.
Scientists at the University of Colorado Boulder have discovered something that experienced ballroom dancers have long known: When dancers are in tune with each other, their brains may sync up, helping them move as one.
“When we dance, our brains are actually coupling,” said Thiago Roque, a graduate student in the Atlas Institute who led the study. “We are synchronizing our brains through our behavior.”
For the unique experiment, the researchers placed electroencephalogram (EEG) caps, or devices that measure electrical activity in the brain, on pairs doing the Argentine Tango—a sensuous dance where a leader and follower hold each other tight while moving together to music.
The chikungunya virus (ChikV) was first isolated during an arthritic disease outbreak in Tanzania in 1952 [1, 2]. ChikV is a mosquito-borne virus that belongs to the Alphavirus genus of the Togaviridae family. ChikV infections have emerged as a global health risk with approximately 16.9 million cases per year [3]. Major symptoms of ChikV infection include severe fever, rashes, and joint pain. Chronic arthritis-like symptoms may persist and can be debilitating [4, 5]. ChikV, a positive-sense RNA virus, encodes 5 structural proteins and 4 nonstructural proteins (NSP1 to NSP4) [6]. Nonstructural protein 3 (NSP3) consists of a conserved macrodomain (Mac1) at the N-terminus, a poorly conserved hypervariable domain, and a central zinc-binding domain known as the alphavirus unique domain [7]. The macrodomain fold is highly conserved across evolution, having been identified in bacteria, algae, and eukaryotes [8, 9]. It has been suggested that ChikV Mac1 suppresses the host immune response through its adenosine diphosphate ribosyl (ADP-ribosyl) hydrolase activity [10], which removes ADP-ribose posttranslational modifications from target host proteins by hydrolyzing mono-ADP-ribosylated aspartate and glutamate residues. Mac1 has therefore emerged as a promising antiviral drug target [10], supported by evidence suggesting that it is a key determinant of ChikV virulence in mice. Despite their therapeutic potential, efforts to identify ChikV inhibitors have had limited success. A fragment screen of ~14,000 compounds identified only weak inhibitors (e.g., 2-pyrimidone-4-carboxylic acid scaffold, with one of the compounds showing IC50 of 23 μM) [11]. Another computational docking and simulation study screened 820 compounds and predicted that natural compounds from plants, including apigetrin, baicalin, baloxavir, luteoloside, rutaecarpine, and amentoflavone [12], are Mac1 inhibitors. The predicted binding affinity of baicalin was −10.8 kcal/mol against ChikV Mac1. Another study identified N-[2-(5-methoxy-1 H-indol-3-yl) ethyl]-2-oxo-1,2-dihydroquinoline-4-carboxamide through virtual screening of 245,532 natural compounds, followed by in vitro validation using a microscale thermophoresis binding assay (binding constant [Kd] of 1.066 × 10−6 ± 0.95 μM) and in vivo inhibition of ChikV replication [13].
Similar to ChikV, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) NSP3 contains 3 tandem macrodomains, with Mac1 serving as the catalytically active macrodomain that binds and hydrolyzes mono-ADP-ribose on posttranslationally modified target host proteins [14,15]. SARS-CoV-2 Mac1 is essential for viral pathogenesis and represents a promising drug target [16,17]. In contrast to ChikV Mac1, it has proven amenable to inhibitor development. An early crystallographic screen of approximately 2,600 compounds revealed 234 fragment structures bound to SARS-CoV-2 Mac1 [18]. Using these hits, several optimized inhibitors were designed, followed by another round of crystallographic screening [19]. Among the resulting top inhibitors was AVI-4206, a potent inhibitor with an IC50 of 20 nM that is effective in an animal model of SARS-CoV-2 infection [20]. Other studies have identified additional promising scaffolds, including 2-amide-3-methylester thiophene scaffold derivatives that bind SARS-CoV-2 Mac1 (IC50 = 1.5 μM) and inhibit viral replication [21], synthetic analogs of ADP-ribose that bind SARS-CoV-2 Mac1 with nanomolar affinity [22], and pyrrolo-pyrimidine-based compounds that inhibit viral replication in SARS-CoV-2 [23].
The structural similarity between ChikV Mac1 and SARS-CoV-2 Mac1 [24] has not translated into similar druggability. One strategy to improve ligand-binding affinity is to exploit the presence of water molecules in the binding site by designing inhibitors that effectively use them to form bridging interactions that strengthen binding to the protein [25]. This strategy is particularly relevant for Mac1 ADP-ribose-binding sites, which are large, solvent exposed, and known to maintain an extensive network of ordered water molecules upon ADP binding. In SARS-CoV-2 Mac1, ADP-ribose forms several water-mediated interactions, resulting in the water network in the ADP-ribose-binding site reorganizing upon ligand binding [18,26].
Scientists from A*STAR Infectious Diseases Labs (A*STAR IDL), Nanyang Technological University, Singapore’s Lee Kong Chian School of Medicine (LKCMedicine), the National University of Singapore (NUS), and international collaborators have uncovered how Mycobacterium abscessus—a bacterium that causes serious lung infections—can evade bacteriophage (phage) therapy, and demonstrated a combination strategy to overcome this resistance, offering a pathway toward more effective and durable treatments. The study was published in the Proceedings of the National Academy of Sciences.
Antimicrobial resistance (AMR) is an escalating health challenge that is expected to place growing strain on health care systems worldwide. As AMR continues to erode the effectiveness of existing antibiotics—with one in six bacterial infections worldwide now resistant to antibiotics—scientists are accelerating efforts to develop new countermeasures such as phage therapy, which uses viruses to target bacteria. These efforts are important for strengthening global health and infectious disease preparedness.
Ever heard of getting a “dopamine hit” from something you enjoy? These exciting moments also appear to influence memory, although perhaps not in the way you’d expect.
New research by UCLA psychologists suggests your brain may use dopamine to distort and expand time between distinct events, separating the flow of experience into pieces that can be flexibly reconstructed in the future.
The study, published in Nature Communications, found that a key dopamine-producing area of the brain—the ventral tegmental area—was activated when volunteers participating in an MRI scan detected the start of a new event. Importantly, when this dopamine hub was strongly activated, people reported more time had passed. The researchers also found that when people blinked more during a new event—an action thought to be related to dopamine signaling—their memory for time once again expanded.
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Sebastian Zieba: “Since LHS 3,844 b lacks such a silicate crust, one may conclude that Earth-like plate tectonics does not apply to this planet, or it is ineffective. This planet likely only contains little water.”
What do the surfaces of rocky exoplanets look like? This is what a recent study published in Nature Astronomy hopes to address as a team of scientists investigated how heat measurements could be used to ascertain the potential physical and chemical properties of a rocky nearby rocky exoplanet. This study has the potential to help scientists use new methods for studying rocky exoplanets, as they are still too far away to be directly observed.
For the study, the researchers used NASA’s powerful James Webb Space Telescope (JWST) to observe the rocky exoplanet LHS 3,844 b, which is located approximately 49 light-years from Earth and whose mass and radius is estimated to be almost 2.5 and 1.3 times of Earth, respectively. LHS 3,844 b orbits inside the interior edge of its star’s habitable zone, making it analog to Mercury. To accomplish this, the researchers used JWST to obtain heat measurements of LHS 3,844 b to ascertain the exoplanet’s potential physical, geological, and chemical properties.
In the end, the researchers found that LHS 3,844 b is likely comprised of a dark, volcanic surface that’s been weathered by space radiation. The team notes that LHS 3,384 b either has a fresh surface or mimics the Moon or Mercury, the latter of which ceased volcanic activity billions of years ago. The team was also able to potentially rule out a distinct geological characteristic that Earth possesses.
“We found that the earlier a region became shadowed, the larger the area that was able to accumulate ice,” said Dr. Oded Aharonson. [ https://www.labroots.com/trending/space/30512/moon-craters-targets-water-ice-2](https://www.labroots.com/trending/space/30512/moon-craters-targets-water-ice-2)
What are the best places on the Moon to find water ice that can be used for future crewed missions to the Moon’s surface? This is what a recent study published in Nature Astronomy hopes to address as a team of scientists investigated potential regions of the Moon where future astronauts could have the highest chance of finding water ice. This study has the potential to help scientists, engineers, mission planners, and future astronauts narrow the scope for finding the best locations of water ice on the Moon to aid in future crewed missions, thus negating the need for water supplies from Earth.
For the study, the researchers analyze data obtained from the Lyman-Alpha Mapping Project (LAMP), which is an instrument on the Lunar Reconnaissance Orbiter designed to map the entire surface of the Moon in far ultraviolet light. They combined these findings with computer models designed to simulate how and when water was delivered to the Moon millions to billions of years ago.
In the end, the researchers found that Shackleton Crater, a portion of which is located directly at the lunar south pole, is not the most ideal location for water ice, which has long been thought. In contrast, the researchers propose that Haworth Crater is the ideal location for finding water ice. Additionally, the researchers found that some of these regions have been building water ice for as long as 1.5 billion years.