RESUMO
N6-methyladenosine (m6A) is a crucial RNA modification that regulates diverse biological processes in human cells, but its co-transcriptional deposition and functions remain poorly understood. Here, we identified the RNA helicase DDX21 with a previously unrecognized role in directing m6A modification on nascent RNA for co-transcriptional regulation. DDX21 interacts with METTL3 for co-recruitment to chromatin through its recognition of R-loops, which can be formed co-transcriptionally as nascent transcripts hybridize onto the template DNA strand. Moreover, DDX21's helicase activity is needed for METTL3-mediated m6A deposition onto nascent RNA following recruitment. At transcription termination regions, this nexus of actions promotes XRN2-mediated termination of RNAPII transcription. Disruption of any of these steps, including the loss of DDX21, METTL3, or their enzymatic activities, leads to defective termination that can induce DNA damage. Therefore, we propose that the R-loop-DDX21-METTL3 nexus forges the missing link for co-transcriptional modification of m6A, coordinating transcription termination and genome stability.
Assuntos
Adenosina , Adenosina/análogos & derivados , RNA Helicases DEAD-box , Exorribonucleases , Instabilidade Genômica , Metiltransferases , Estruturas R-Loop , RNA Polimerase II , Terminação da Transcrição Genética , Humanos , RNA Helicases DEAD-box/metabolismo , RNA Helicases DEAD-box/genética , Metiltransferases/metabolismo , Metiltransferases/genética , Adenosina/metabolismo , Adenosina/genética , Exorribonucleases/metabolismo , Exorribonucleases/genética , RNA Polimerase II/metabolismo , RNA Polimerase II/genética , Células HEK293 , Cromatina/metabolismo , Cromatina/genética , Dano ao DNA , Células HeLa , RNA/metabolismo , RNA/genética , Transcrição Gênica , Metilação de RNARESUMO
A new perovskite KOsO_{3} has been stabilized under high-pressure and high-temperature conditions. It is cubic at 500 K (Pm-3m) and undergoes subsequent phase transitions to tetragonal at 320 K (P4/mmm) and rhombohedral (R-3m) at 230 K as shown from refining synchrotron x-ray powder diffraction (SXRD) data. The larger orbital overlap integral and the extended wave function of 5d electrons in the perovskite KOsO_{3} allow to explore physics from the regime where Mott and Hund's rule couplings dominate to the state where the multiple interactions are on equal footing. We demonstrate an exotic magnetic ordering phase found by neutron powder diffraction along with physical properties via a suite of measurements including magnetic and transport properties, differential scanning calorimetry, and specific heat, which provide comprehensive information for a system at the crossover from localized to itinerant electronic behavior.
RESUMO
We propose a methodology to mitigate angular color variation in full-color micron-scale LED arrays. By simulating light field distribution for red (AlGaAs) and green/blue (GaN) light across various RGB micro-LED sizes, we can select matching light field patterns for RGB chips, reducing angular color variation from 0.0201 to 0.0030. Applying this method to full-color mini-LED assemblies achieves a reduction from 0.0128 to 0.0032 by matching light field patterns with varying substrate thicknesses. This straightforward approach aligns with current mass transfer processes, offering practical implementation.
RESUMO
The vertical flow (VF) method improves generation and collection efficiency in Raman spectroscopy. It enhances all Raman signals, including undesired signals of organic solvents having a considerably large Raman cross section. We constructed a Raman spectrometer using the VF method to overcome this drawback and introduced a spatial line rejection mask to eliminate unnecessary bands. In addition, the design of the VF unit was improved to resist organic solvents. A VF unit with a 60-µm pinhole enhanced the signal 168 times. The spatial mask effectively eliminated the large Raman bands of the solvent and enabled a longer exposure time. The increase in the dynamic range improved the signal-to-noise ratio by 10 % in methanol and acetonitrile measurements. Raman spectrometer with the VF method and spatial mask enables us to record the Raman spectrum of solute molecules without the disturbance of solvent bands.
RESUMO
Copper clusters feature prominently in both metalloenzymes and synthetic nanoclusters that mediate catalytic redox transformations of gaseous small molecules. Such reactions are critical to biological energy conversion and are expected to be crucial parts of renewable energy economies. However, the precise roles of individual metal atoms within clusters are difficult to elucidate, particularly for cluster systems that are dynamic under operating conditions. Here, we present a metal site-specific analysis of synthetic Cu4(µ4-S) clusters that mimic the Cu Z active site of the nitrous oxide reductase enzyme. Leveraging the ability to obtain structural snapshots of both inactive and active forms of the synthetic model system, we analyzed both states using resonant X-ray diffraction anomalous fine structure (DAFS), a technique that enables X-ray absorption profiles of individual metal sites within a cluster to be extracted independently. Using DAFS, we found that a change in cluster geometry between the inactive and active states is correlated to Cu site differentiation that is presumably required for efficient activation of N2O gas. More precisely, we hypothesize that the Cu δ+â¯Cu δ- pairs produced upon site differentiation are poised for N2O activation, as supported by computational modeling. These results provide an unprecedented level of detail on the roles of individual metal sites within the synthetic cluster system and how those roles interplay with cluster geometry to impact the reactivity function. We expect this fundamental knowledge to inform understanding of metal clusters in settings ranging from (bio)molecular to nanocluster to extended solid systems involved in energy conversion.
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Since the onset of the COVID-19 pandemic in 2019, the role of weather conditions in influencing transmission has been unclear, with results varying across different studies. Given the changes in border policies and the higher vaccination rates compared to earlier conditions, this study aimed to reassess the impact of weather on COVID-19, focusing on local climate effects. We analyzed daily COVID-19 case data and weather factors such as temperature, humidity, wind speed, and a diurnal temperature range from 1 March to 15 August 2022 across six regions in Taiwan. This study found a positive correlation between maximum daily temperature and relative humidity with new COVID-19 cases, whereas wind speed and diurnal temperature range were negatively correlated. Additionally, a significant positive correlation was identified between the unease environmental condition factor (UECF, calculated as RH*Tmax/WS), the kind of Climate Factor Complex (CFC), and confirmed cases. The findings highlight the influence of local weather conditions on COVID-19 transmission, suggesting that such factors can alter environmental comfort and human behavior, thereby affecting disease spread. We also introduced the Fire-Qi Period concept to explain the cyclic climatic variations influencing infectious disease outbreaks globally. This study emphasizes the necessity of considering both local and global climatic effects on infectious diseases.
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Enterovirus infection and enterovirus infection with severe complications (EVSC) are critical issues in several aspects. However, there is no suitable predictive tool for these infections. A climate factor complex (CFC) containing several climate factors could provide more effective predictions. The ping-year factor (PYF) and El Niño-Southern Oscillation (ENSO) are possible CFCs. This study aimed to determine the relationship between these two CFCs and the incidence of enterovirus infection. Children aged 15 years and younger with enterovirus infection and/or EVSC were enrolled between 2007 and 2022. Each year was categorized into a ping-year or non-ping-year according to the PYF. Poisson regression was used to evaluate the associations between the PYF, ENSO, and the incidence of enterovirus infection. Compared to the ping-year group, the incidence rate of enterovirus infection, the incidence rate of EVSC, and the ratio of EVSC in the non-ping-year group were 1.24, 3.38, and 2.73 times higher, respectively (p < 0.001). For every one-unit increase in La Niña, the incidence rate of enterovirus infection decreased to 0.96 times (p < 0.001). Our study indicated that CFCs could be potential predictors for enterovirus infection, and the PYF was more suitable than ENSO. Further research is needed to improve the predictive model.
Assuntos
El Niño Oscilação Sul , Infecções por Enterovirus , Criança , Humanos , Taiwan/epidemiologia , Mudança Climática , Incidência , Infecções por Enterovirus/epidemiologiaRESUMO
The design and synthesis of polyhedra using coordination-driven self-assembly has been an intriguing research area for synthetic chemists. Metal-organic polyhedra are a class of intricate molecular architectures that have garnered significant attention in the literature due to their diverse structures and potential applications. Hereby, we report Cu-MOP, a bifunctional metal-organic cuboctahedra built using 2,6-dimethylpyridine-3,5-dicarboxylic acid and copper acetate at room temperature. The presence of both Lewis basic pyridine groups and Lewis acidic copper sites imparts catalytic activity to Cu-MOP for the tandem one-pot deacetalization-Knoevenagel/Henry reactions. The effect of solvent system and time duration on the yields of the reactions was studied, and the results illustrate the promising potential of these metal-organic cuboctahedra, also known as nanoballs for applications in catalysis.
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BACKGROUND: Subarachnoid hemorrhage (SAH) is a life-threatening neurological disease that usually has a poor prognosis. Neurogenesis is a potential therapeutic target for brain injury. Ketone metabolism also plays neuroprotective roles in many neurological disorders. OXCT1 (3-Oxoacid CoA-Transferase 1) is the rate-limiting enzyme of ketone body oxidation. In this study, we explored whether increasing ketone oxidation by upregulating OXCT1 in neurons could promote neurogenesis after SAH, and evaluated the potential mechanism involved in this process. METHODS: The ß-hydroxybutyrate content was measured using an enzymatic colorimetric assay. Adeno-associated virus targeting neurons was injected to overexpress OXCT1, and the expression and localization of proteins were evaluated by western blotting and immunofluorescence staining. Adult hippocampal neurogenesis was evaluated by dual staining with doublecortin and 5-Ethynyl-2'-Deoxyuridine. LY294002 was intracerebroventricularly administered to inhibit Akt activity. The Morris water maze and Y-maze tests were employed to assess cognitive function after SAH. RESULTS: The results showed that OXCT1 expression and hippocampal neurogenesis significantly decreased in the early stage of SAH. Overexpression of OXCT1 successfully increased hippocampal neurogenesis via activation of Akt/GSK-3ß/ß-catenin signaling and improved cognitive function, both of which were reversed by administration of LY294002. CONCLUSIONS: OXCT1 regulated hippocampal ketone body metabolism and increased neurogenesis through mechanisms mediated by the Akt/GSK-3ß/ß-catenin pathway, improving cognitive impairment after SAH.
Assuntos
Coenzima A-Transferases , Disfunção Cognitiva , Hipocampo , Neurogênese , Hemorragia Subaracnóidea , Ácido 3-Hidroxibutírico , beta Catenina , Coenzima A-Transferases/genética , Coenzima A-Transferases/metabolismo , Glicogênio Sintase Quinase 3 beta , Hipocampo/crescimento & desenvolvimento , Proteínas Proto-Oncogênicas c-akt , Animais , CamundongosRESUMO
Stepwise metalation of the hexadentate ligand tbsLH6 (tbsLH6 = 1,3,5-C6H9(NHC6H4-o-NHSiMe2tBu)3) affords bimetallic trinuclear clusters (tbsL)Fe2Zn(thf) and (tbsL)Fe2Zn(py). Reactivity studies were pursued to understand metal atom lability as the clusters undergo ligand substitution, redox chemistry, and group transfer processes. Chloride addition to (tbsL)Fe2Zn(thf) resulted in a mixture of species including both all-zinc and all-iron products. Addition of ArN3 (Ar = Ph, 3,5-(CF3)2C6H3) to (tbsL)Fe2Zn(py) yielded a mixture of two trinuclear products: (tbsL)Fe3(µ3-NAr) and (tbsL)Fe2Zn(µ3-NAr)(py). The two imido species were separated via crystallization, and outer sphere reduction of (tbsL)Fe2Zn(µ3-NAr)(py) resulted in the formation of a single product, [2,2,2-crypt(K)][(tbsL)Fe2Zn(µ3-NAr)]. These results provide insight into the relationship between heterometallic cluster structure and substitutional lability and could help inform both future catalyst design and our understanding of metal atom lability in bioinorganic systems.
RESUMO
Charge density waves (CDWs) involved with electronic and phononic subsystems simultaneously are a common quantum state in solid-state physics, especially in low-dimensional materials. However, CDW phase dynamics in various dimensions are yet to be studied, and their phase transition mechanism is currently moot. Here we show that using the distinct temperature evolution of orientation-dependent ultrafast electron and phonon dynamics, different dimensional CDW phases are verified in CuTe. When the temperature decreases, the shrinking of c-axis length accompanied with the appearance of interchain and interlayer interactions causes the quantum fluctuations (QF) of the CDW phase until 220 K. At T < 220 K, the CDWs on the different ab-planes are finally locked with each other in anti-phase to form a CDW phase along the c-axis. This study shows the dimension evolution of CDW phases in one CDW system and their stabilized mechanisms in different temperature regimes.