Targeted protein degradation has emerged as a novel therapeutic paradigm in drug discovery. Despite the FDA approval of anaplastic lymphoma kinase (ALK) inhibitors, the pursuit of compounds with enhanced potency and prolonged efficacy remains crucial to mitigate inevitable adverse effects. In this context, we endeavored to develop ALK degraders utilizing FDA-approved ALK inhibitors-crizotinib, ceritinib, brigatinib, and alectinib-as ALK binders, along with 4-methoxyphenylfumarate as a covalent handle to bind to RNF126 E3 ligase.
View Article and Find Full Text PDFBiotechnol Lett
November 2024
The monooxygenase activity of engineered CYP102A1 on α-terpineol was investigated. CYP102A1 M850 mutant (F11Y/R47L/D68G/F81I/F87V/E143G/L188Q/E267V/H408R) showed the highest catalytic activity toward α-terpineol among the engineered mutants produced by random mutagenesis. The major product (P1) of α-terpineol, p-menth-1-ene-3,8-diol, was characterized by high-performance liquid chromatography, gas-chromatography mass spectrometry, and nuclear magnetic resonance spectroscopy.
View Article and Find Full Text PDFIntroduction: The adoption of tethered mobile personal health records provides not only medical information to patients but also various convenience functions related to hospital use, thereby increasing accessibility to healthcare services and promoting patient engagement. We analyse the tethered mobile personal health records app's usage logs to determine how it can contribute to improving medical service accessibility and patient engagement.
Methods: Log data, that comprised menu type, log time, and date, were collected from the mobile personal health records app of a tertiary referral hospital.
The Patagonian toothfish (Dissostichus eleginoides) belongs to the Actinopterygii class, and the suborder Notothenioidei, which lives in cold waters in the Southern Hemisphere. We performed assembly and annotation, and we integrated the Illumina short-read sequencing for polishinng, PacBio long-read sequencing for contig-level assembly, and Hi-C sequencing technology to obtain high-quality of chromosome-level genome assembly. The final assembly analysis resulted in a total of 495 scaffolds, a genome size of 844.
View Article and Find Full Text PDFBehavioral sensitization is defined as the heightened and persistent behavioral response to repeated drug exposure as a manifestation of drug craving. Psychomotor stimulants such as cocaine can induce strong behavioral sensitization. In this study, we explored the effects of optogenetic stimulation of the prelimbic (PL) to the nucleus accumbnes (NAc) core on the expression of cocaine-induced behavioral sensitization.
View Article and Find Full Text PDFThis study assessed the seasonal distribution and factors associated with PM in nationwide subway stations in Korea. A total of 229,644 data points collected over one year were used to determine one-day PM concentrations from 642 subway stations. The geometric mean of indoor PM concentrations was 26.
View Article and Find Full Text PDFEzrin-Radixin-Moesin (ERM) proteins are actin-binding proteins that contribute to morphological changes in dendritic spines. Despite their significant role in regulating spine structure, the role of ERM proteins in the nucleus accumbnes (NAcc) is not well known, especially in in the context of risk-reward decision-making. Here, we measured the relationship between synaptic excitation and inhibition (E/I ratio) from medium spiny neurons in the NAcc core obtained in the rat after a rat gambling task (rGT).
View Article and Find Full Text PDFEnzyme Microb Technol
October 2024
Perillyl alcohol (POH) is a secondary metabolite of plants. POH and its derivatives are known to be effective as an anticancer treatment. In this study, oxidative derivatives of POH, which are difficult to synthesize chemically, were synthesized using the engineered bacterial cytochrome P450 BM3 (CYP102A1) as a biocatalyst.
View Article and Find Full Text PDFThe underwater soundscape was recorded in Seaview Bay off Inexpressible Island, Ross Sea region Marine protected area, for 3 days in December 2021. Leopard seal vocalizations were a prominent sound source that led to variations in ambient sound pressure levels in a frequency range of approximately 150-4500 Hz. Among the 14 call types previously identified, except ultrasound vocalizations, six types of broadcast calls were classified, and their acoustic characteristics were analyzed.
View Article and Find Full Text PDFBackground: The development of the secondary palate, an essential process for hard palate formation, involves intricate cellular processes. Here, the authors examined the expression patterns of palatal fusion-associated genes in postdevelopmental human palatal tissues.
Methods: Mucosal samples collected from the anterior fused (control; n =5) and posterior unfused regions (study; n =5) of cleft palate patients were subjected to RNA sequencing.
The potential role of the ghrelin receptor, also known as the growth hormone secretagogue receptor (GHSR), within the nucleus accumbens (NAcc) in regulating drug addiction and feeding has been documented; however, the pattern of its expression in this site remains elusive. In this study, we characterized the expression patterns of GHSR1a and 1b, two subtypes of GHSRs, within the NAcc of the rat brain by immunohistochemistry. We visually detected GHSR signals, for the first time, at the protein level in the NAcc in which they were mostly expressed in neurons including both medium spiny neurons (MSNs) and non-MSNs.
View Article and Find Full Text PDFWe investigated the recent spatial variation in the mesozooplankton community on the broad shelf of the RSR MPA during the bloom season. The mesozooplankton community was geographically divided into three regions: the Terra Nova Bay polynya, the Ross Sea polynya, and the marginal polynya. Larval euphausiids were dominant in the two polynya regions, whereas copepods were predominant in the marginal polynya region.
View Article and Find Full Text PDFCMOS-RRAM integration holds great promise for low energy and high throughput neuromorphic computing. However, most RRAM technologies relying on filamentary switching suffer from variations and noise, leading to computational accuracy loss, increased energy consumption, and overhead by expensive program and verify schemes. We developed a filament-free, bulk switching RRAM technology to address these challenges.
View Article and Find Full Text PDFThe mitogenome of collected from the Ross Sea Region Marine Protected Area (RSR MPA) is described for the first time. The assembled mitogenome was 17,291 bp in length and consisted of two ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs), 13 protein-coding genes (PCGs), and noncoding regions, all of which were identical to those of other euphausiid species. The most common start codon for the 13 PCGs was ATG, and the most common termination codon was TAA.
View Article and Find Full Text PDFMercury (Hg) biomonitoring requires a precise understanding of the internal processes contributing to disparities between the Hg sources in the environment and the Hg measured in the biota. In this study, we investigated the use of Hg stable isotopes to trace Hg accumulation in Adélie and emperor penguin chicks from four breeding colonies in Antarctica. Interspecific variation of ΔHg in penguin chicks reflects the distinct foraging habitats and Hg exposures in adults.
View Article and Find Full Text PDFQuantum computers offer significant potential for complex system analysis, yet their application in large systems is hindered by limitations such as qubit availability and quantum hardware noise. While the variational quantum eigensolver (VQE) was proposed to address these issues, its scalability remains limited. Many efforts, including new ansätze and Hamiltonian modifications, have been made to overcome these challenges.
View Article and Find Full Text PDFOptically transparent neural microelectrodes have facilitated simultaneous electrophysiological recordings from the brain surface with the optical imaging and stimulation of neural activity. A remaining challenge is to scale down the electrode dimensions to the single-cell size and increase the density to record neural activity with high spatial resolution across large areas to capture nonlinear neural dynamics. Here we developed transparent graphene microelectrodes with ultrasmall openings and a large, transparent recording area without any gold extensions in the field of view with high-density microelectrode arrays up to 256 channels.
View Article and Find Full Text PDFThe Antarctic whitefin plunderfish Pogonophryne albipinna belongs to the family Artedidraconidae, a key component of Antarctic benthic ecosystems within the order Perciformes and the suborder Notothenioidei. While genome research on P. albipinna using short-read sequencing is available, high-quality genome assembly and annotation employing long-read sequencing have yet to be performed.
View Article and Find Full Text PDFThe rapid development of 6G communications using terahertz (THz) electromagnetic waves has created a demand for highly sensitive THz nanoresonators capable of detecting these waves. Among the potential candidates, THz nanogap loop arrays show promising characteristics but require significant computational resources for accurate simulation. This requirement arises because their unit cells are 10 times smaller than millimeter wavelengths, with nanogap regions that are 1 000 000 times smaller.
View Article and Find Full Text PDFCYP102A1 from is an important enzyme in biotechnology, because engineered CYP102A1 enzymes can react with diverse substrates and produce human cytochrome P450-like metabolites. Therefore, CYP102A1 can be applied to drug metabolite production. Terpinen-4-ol is a cyclic monoterpene and the primary component of essential tea tree oil.
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