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Inhibiting epigenetic modulators can transcriptionally reactivate transposable elements (TEs). These TE transcripts often generate unique peptides that can serve as immunogenic antigens for immunotherapy. Here, we ask whether TEs activated by epigenetic therapy could appreciably increase the antigen repertoire in glioblastoma, an aggressive brain cancer with low mutation and neoantigen burden. We treated patient-derived primary glioblastoma stem cell lines, an astrocyte cell line and primary fibroblast cell lines with epigenetic drugs, and identified treatment-induced, TE-derived transcripts that are preferentially expressed in cancer cells. We verified that these transcripts could produce human leukocyte antigen class I-presented antigens using liquid chromatography with tandem mass spectrometry pulldown experiments. Importantly, many TEs were also transcribed, even in proliferating nontumor cell lines, after epigenetic therapy, which suggests that targeted strategies like CRISPR-mediated activation could minimize potential side effects of activating unwanted genomic regions. The results highlight both the need for caution and the promise of future translational efforts in harnessing treatment-induced TE-derived antigens for targeted immunotherapy.
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BACKGROUND: Previous studies reported that short-term exposure to ground-level ozone is associated with mortality risk. However, due to the limited monitored areas, existing studies were limited in assessing the nationwide risk and suggesting specific vulnerable populations to the ozone-mortality risk. METHODS: We performed a nationwide time-stratified case-crossover study to evaluate the association between short-term ozone and cause-specific mortality in South Korea (2015-2019). A machine learning-ensemble prediction model (a test R2 > 0.96) was used to assess the short-term ozone exposure. Stratification analysis was conducted to examine the high-risk populations, and the excess mortality due to non-compliance with the WHO guideline was also assessed. RESULTS: For all-cause mortality (1,343,077 cases), the risk associated with ozone (lag0- 1) was weakly identified (odd ratio: 1.005 with 95% CI: 0.997-1.014), and the risk was prominent in mortality with circulatory system diseases. In addition, based on the point estimates, the ozone-mortality risk was higher in people aged less than 65y, and this pattern was also observed in circulatory system disease deaths and urban areas. CONCLUSIONS: This study provides national estimates of mortality risks associated with short-term ozone. Results showed that the benefits of stricter air quality standards could be greater in vulnerable populations.
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The Geostationary Environment Monitoring Spectrometer (GEMS) is the world's first geostationary instrument that monitors hourly gaseous air pollutant levels, including nitrogen dioxide (NO2). Using the first-of-its-kind capabilities of GEMS NO2 data, we examined how well GEMS NO2 levels can explain the spatiotemporal variabilities in hourly NO2 concentrations in the Republic of Korea for the year 2022. A correlation analysis between hourly GEMS NO2 levels and ground NO2 concentrations showed a higher spatial correlation [Pearson r = 0.56 (SD = 0.20)] than a temporal one [Pearson r = 0.42 (SD = 0.14)], on average. To take advantage of the enhanced spatial predictability of GEMS NO2 data, we employed a mixed effects model to allow hour-specific relationships between GEMS NO2 and NO2 concentrations on a given day in each region and subsequently estimated hourly NO2 concentrations in all urban and rural areas. The 10-fold cross validation demonstrated R2 = 0.72, mean absolute error (MAE) = 3.7 ppb, and root mean squared error (RMSE) = 5.5 ppb. The hourly variations of the relationships were attributed particularly to those of wind speed among meteorological parameters considered in this study. The spatial distributions of hourly estimated NO2 concentrations were highly correlated between hours [average r = 0.91 (SD = 0.06)]. Nonetheless, they represented the diurnal patterns of urban versus rural NO2 contrasts during the day [urban/rural NO2 ratios from 1.22 (5 p.m.) to 1.37 (12 p.m.)]. The newly retrieved GEMS NO2 data enable temporally as well as spatially resolved NO2 exposure assessment. In combination with the time-activity patterns of individual subjects, the GEMS NO2 data can generate 'sub-population' exposure estimates and therefore enhance health effect studies.
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Particulate matter with an aerodynamic diameter of ≤2.5 µm (PM2.5) can infiltrate deep into the respiratory system, posing significant health risks. Notably, the health burden of PM2.5 is more pronounced among the older adult population. With an aging population, the public health burden attributable to PM2.5 could escalate even if the current PM2.5 level remains stable. This study evaluated the number of deaths attributable to long-term PM2.5 exposure in the Republic of Korea between 2020 and 2050 and identified the PM2.5 concentration required at least to maintain the current PM2.5 health burden. To calculate mortality for 2020-2050, we performed a health impact assessment using 3-year (2019-2021) average population-weighted PM2.5 concentrations, age-specific population and mortality rates. In 2020, 33,578 [95% confidence interval (CI) = 31,708-35,448] deaths were attributable to PM2.5 exposure. Projecting forward, if the 2019-2021 average PM2.5 level remains constant, mortality is projected to be 112,953 (95% CI = 109,963-115,943) in 2050, more than three times higher than in 2020. To maintain the same level of health burden in 2050 as in 2020, the PM2.5 concentration needs to be immediately reduced to 5.8 µg/m3. In an age-specific analysis, the proportion of older adults (ages 65+) to total mortality would increase from 83% (2020) to 96% (2050), indicating that the rising mortality is predominantly driven by the aging population. By region, the reduction of PM2.5 concentrations, which is required immediately in 2020 to have the health burden in 2050 equal to that in 2020, varied from 3.6 µg/m3 in Goheung-gun (25% reduction) to 20.8 µg/m3 in Heungdeok-gu (82% reduction). Our study emphasizes the critical need for air quality management to consider aging populations when establishing PM2.5 air quality standards, as well as their associated policies and regulations.
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Poluentes Atmosféricos , Exposição Ambiental , Material Particulado , Saúde Pública , República da Coreia , Material Particulado/análise , Humanos , Exposição Ambiental/efeitos adversos , Poluentes Atmosféricos/análise , Idoso , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Adulto , Poluição do Ar/análise , Poluição do Ar/efeitos adversos , Adulto Jovem , Envelhecimento , Adolescente , Mortalidade/tendências , Criança , Pré-EscolarRESUMO
This study developed an advanced 850 nm centered distributed Bragg reflector (DBR) (broadband DBR) composed of nanomaterial-based multiple structures to improve the optical efficiency of an 850 nm near-infrared light-emitting diode (NIR-LED). A combined 850 nm centered broadband DBR was fabricated by growing an 800 nm centered ten-pair DBR on a 900 nm centered ten-pair DBR (denoted as a combined DBR). The combined DBR exhibited a slightly wider peak band than conventional DBRs. Furthermore, the peak band width of the combined DBR significantly increased upon using a reflective AlAs buffer layer that reduced the overlapped reflection. The output power (20.5 mW) of NIR-LED chips using the combined DBR with an AlAs buffer layer exceeded that of a conventional 850 nm centered DBR (14.5 mW) by more than 40%. Results indicated that combining the optical conditions of wavelengths and the AlAs buffer layer effectively strengthened the broadband effect of the DBR and increased the optical efficiency of the 850 nm NIR-LED.
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In the original publication [...].
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Owing to their superior stability compared to those of conventional molecular dyes, as well as their high UV-visible absorption capacity, which can be tuned to cover the majority of the solar spectrum through size adjustment, quantum dot (QD)/TiO2 composites are being actively investigated as photosensitizing components for diverse solar energy conversion systems. However, the conversion efficiencies and durabilities of QD/TiO2-based solar cells and photocatalytic systems are still inferior to those of conventional systems that employ organic/inorganic components as photosensitizers. This is because of the poor adsorption of QDs onto the TiO2 surface, resulting in insufficient interfacial interactions between the two. The mechanism underlying QD adsorption on the TiO2 surface and its relationship to the photosensitization process remain unclear. In this study, we established that the surface characteristics of the TiO2 semiconductor and the QDs (i.e., surface defects of the metal oxide and the surface structure of the QD core) directly affect the QD adsorption capacity by TiO2 and the interfacial interactions between the QDs and TiO2, which relates to the photosensitization process from the photoexcited QDs to TiO2 (QD* â TiO2). The interfacial interaction between the QDs and TiO2 is maximized when the shape/thickness-modulated triangular QDs are composited with defect-rich anatase TiO2. Comprehensive investigations through photodynamic analyses and surface evaluation using X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), and photocatalysis experiments collectively validate that tuning the surface properties of QDs and modulating the TiO2 defect concentration can synergistically amplify the interfacial interaction between the QDs and TiO2. This augmentation markedly improved the efficiency of photoinduced electron transfer from the photoexcited QDs to TiO2, resulting in significantly increased photocatalytic activity of the QD/TiO2 composite. This study provides the first in-depth characterization of the physical adhesion of QDs dispersed on a heterogeneous metal-oxide surface. Furthermore, the prepared QD/TiO2 composite exhibits exceptional adsorption stability, resisting QD detachment from the TiO2 surface over a wide pH range (pH = 2-12) in aqueous media as well as in nonaqueous solvents during two months of immersion. These findings can aid the development of practical QD-sensitized solar energy conversion systems that require the long-term stability of the photosensitizing unit.
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BACKGROUND: To improve gait disability in patients with chronic stroke, ankle muscle strengthening and calf muscle stretching exercises are required. However, currently available ankle training equipment limit ankle exercises based on the position. Recently developed ankle training equipment enables spring resistance-based plantar press exercises to be performed in the standing position with weight support. OBJECTIVE: To conduct a usability test of the ankle training equipment in the standing position by stroke patients with hemiplegic gait and verify its effects on ankle movements. METHODS: The ankle training equipment was applied to five patients with chronic stroke and hemiplegic gait. In the standing position, the patients performed forefoot and rearfoot press exercises in the affected side with a day's interval at 20 repetitions maximum (RM). During the exercises, surface electromyography (sEMG) was used to measure the maximum voluntary isometric contraction (%MVIC) of the leg muscles. The System Usability Scale (SUS) was used to assess the ankle training equipment. Wilcoxon signed-rank test was used to evaluate the differences in muscle activity between the two exercises. RESULTS: Forefoot and rearfoot press exercises increased the %MVIC in the biceps femoris. Additionally, the tibialis anterior and medial gastrocnemius activity was significantly different between the two exercises. The SUS was 78.75% (SD 12.7). CONCLUSION: The usability test of the passive-control foot press trainer (PFPT) that with improvements in the structure and functions for convenience, it could be commercialized. PFPT could be an alternative to the ankle rehabilitation robot that necessitates a sitting position.
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Transtornos Neurológicos da Marcha , Acidente Vascular Cerebral , Humanos , Tornozelo , Posição Ortostática , Articulação do Tornozelo , Acidente Vascular Cerebral/complicações , Músculo Esquelético/fisiologia , Eletromiografia , Marcha/fisiologiaRESUMO
This study investigated a reflective transparent structure to improve the optical efficiency of 850 nm infrared light-emitting diodes (IR-LEDs), by effectively enhancing the number of extracted photons emitted from the active region. The reflective transparent structure was fabricated by combining transparent epitaxial and reflective bonding structures. The transparent epitaxial structure was grown by the liquid-phase epitaxy method, which efficiently extracted photons emitted from the active area in IR-LEDs, both in the vertical and horizontal directions. Furthermore, a reflective bonding structure was fabricated using an omnidirectional reflector and a eutectic metal, which efficiently reflected the photons emitted downwards from the active area in an upward direction. To evaluate reflective transparent IR-LED efficiency, a conventional absorbing substrate infrared light-emitting diode (AS IR-LED) and a transparent substrate infrared light-emitting diode (TS IR-LED) were fabricated, and their characteristics were analyzed. Based on the power-current (L-I) evaluation results, the output power (212 mW) of the 850 nm IR-LED with the reflective transparent structure increased by 76% and 26%, relative to those of the AS IR-LED (121 mW) and TS IR-LED (169 mW), respectively. Furthermore, the reflective transparent structure possesses both transparent and reflective properties, as confirmed by photometric and radial theta measurements. Therefore, light photons emitted from the active area of the 850 nm IR-LED were efficiently extracted upward and sideways, because of the reflective transparent structure.
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The Al/Au alloy was investigated to improve the ohmic characteristic and light efficiency of reflective infrared light-emitting diodes (IR-LEDs). The Al/Au alloy, which was fabricated by combining 10% aluminum and 90% gold, led to considerably improved conductivity on the top layer of p-AlGaAs of the reflective IR-LEDs. In the wafer bond process required for fabricating the reflective IR-LED, the Al/Au alloy, which has filled the hole patterns in Si3N4 film, was used for improving the reflectivity of the Ag reflector and was bonded directly to the top layer of p-AlGaAs on the epitaxial wafer. Based on current-voltage measurements, it was found that the Al/Au alloyed material has a distinct ohmic characteristic pertaining to the p-AlGaAs layer compared with those of the Au/Be alloy material. Therefore, the Al/Au alloy may constitute one of the favored approaches for overcoming the insulative reflective structures of reflective IR-LEDs. For a current density of 200 mA, a lower forward voltage (1.56 V) was observed from the wafer bond IR-LED chip made with the Al/Au alloy; this voltage was remarkably lower in value than that of the conventional chip made with the Au/Be metal (2.29 V). A higher output power (182 mW) was observed from the reflective IR-LEDs made with the Al/Au alloy, thus displaying an increase of 64% compared with those made with the Au/Be alloy (111 mW).
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Four sterically distorted quaterpyridyl (qpy) ligand-bridged Ir(III)-Re(I) heterometallic complexes (Ir-qpymm-Re, Ir-qpymp-Re, Ir-qpypm-Re, and Ir-qpypp-Re), in which the position of the coupling pyridine unit of the two 2,2'-bipyridine ligands was varied (meta (m)- or para (p)-position), pypyx-pyxpy (x = m and m, qpymm; x = m and p, qpymp; x = p and m, qpypm; x = p and p, qpypp), were prepared, along with the fully π-conjugated Ir(III)-[π linker]-Re(I) complexes (π linker = 2,2'-bipyrimidine (bpm), Ir-bpm-Re; π linker = 2,5-di(pyridin-2-yl)pyrazine (dpp), Ir-dpp-Re) to elucidate the electron mediating and accumulative charge separation properties of the bridging π-linker in a bimetallic system (photosensitizer-π linker-catalytic center). From the photophysical and electrochemical studies, it was found that the quaterpyridyl (qpy) bridging ligand (BL), in which the two planar Ir/Re metalated bipyridine (bpy) ligands were connected but slightly canted relative to each other, linking the heteroleptic Ir(III) photosensitizer, [(piqC^N)2IrIII(bpy)]+, and catalytic Re(I) complex, (bpy)ReI(CO)3Cl, minimized the energy lowering of the qpy BL, which hampers the forward photoinduced electron transfer (PET) process from [(piqC^N)2IrIII(N^N)]+ to (N^N)ReI(CO)3Cl (Ered1 = -(0.85-0.93) V and Ered2 = -(1.15-1.30) V vs SCE). This result contrasts with the fully π-delocalized bimetallic systems (Ir-bpm-Re and Ir-dpp-Re) that show a significant energy reduction due to the considerable π-extension and deshielding effect caused by the neighboring Lewis acidic metals (Ir and Re) on the electrochemical scale (Ered1 = -0.37 V and Ered2 = -1.02 and -0.99 V vs SCE). Based on a series of anion absorption studies and spectroelectrochemical (SEC) analyses, all Ir(III)-BL-Re(I) bimetallic complexes were found to exist as dianionic form (Ir(III)-[BL]2--Re(I)) after a fast reductive-quenching process in the presence of excess electron donor. In the photolysis experiment, the four Ir-qpy-Re complexes displayed the reasonable photochemical CO2-to-CO conversion activities (TON of 366-588 for 19 h) owing to the moderated electronic coupling between two functional Ir(III) and Re(I) centers through the slightly distorted qpy ligand, whereas Ir-bpm-Re and Ir-dpp-Re displayed negligible performances as a result of the strong electronic coupling via π-conjugation between the two functional components resulting in the energetic constraints for PET and an unwanted side reactions competing with the forward processes. These results confirm that the qpy unit can be utilized as an efficient BL platform in π-linked bimetallic systems.
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Previous urinary tract infections (UTIs) can predispose one to future infections; however, the underlying mechanisms affecting recurrence are poorly understood. We previously found that UTIs in mice cause differential bladder epithelial (urothelial) remodelling, depending on disease outcome, that impacts susceptibility to recurrent UTI. Here we compared urothelial stem cell (USC) lines isolated from mice with a history of either resolved or chronic uropathogenic Escherichia coli (UPEC) infection, elucidating evidence of molecular imprinting that involved epigenetic changes, including differences in chromatin accessibility, DNA methylation and histone modification. Epigenetic marks in USCs from chronically infected mice enhanced caspase-1-mediated cell death upon UPEC infection, promoting bacterial clearance. Increased Ptgs2os2 expression also occurred, potentially contributing to sustained cyclooxygenase-2 expression, bladder inflammation and mucosal wounding-responses associated with severe recurrent cystitis. Thus, UPEC infection acts as an epi-mutagen reprogramming the urothelial epigenome, leading to urothelial-intrinsic remodelling and training of the innate response to subsequent infection.
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Infecções por Escherichia coli , Infecções Urinárias , Escherichia coli Uropatogênica , Camundongos , Animais , Escherichia coli Uropatogênica/genética , Imunidade Treinada , Infecções Urinárias/microbiologia , Bexiga Urinária/microbiologia , Infecções por Escherichia coli/microbiologiaRESUMO
Understanding the impact of DNA methylation within different disease contexts often requires accurate assessment of these modifications in a genome-wide fashion. Frequently, patient-derived tissues stored in long-term hospital tissue banks have been preserved using formalin-fixation paraffin-embedding (FFPE). While these samples can comprise valuable resources for studying disease, the fixation process ultimately compromises the DNA's integrity and leads to degradation. Degraded DNA can complicate CpG methylome profiling using traditional techniques, particularly when performing methylation-sensitive restriction enzyme sequencing (MRE-seq), yielding high backgrounds and resulting in lowered library complexity. Here, we describe Capture MRE-seq, a new MRE-seq protocol tailored to preserving unmethylated CpG information when using samples with highly degraded DNA. The results using Capture MRE-seq correlate well (0.92) with traditional MRE-seq calls when profiling non-degraded samples, and can recover unmethylated regions in highly degraded samples when traditional MRE-seq fails, which we validate using bisulfite sequencing-based data (WGBS) as well as methylated DNA immunoprecipitation followed by sequencing (MeDIP-seq).
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Metilação de DNA , DNA , Humanos , Ilhas de CpG , DNA/genética , Análise de Sequência de DNA/métodos , GenomaRESUMO
Background/purpose: Due to their regenerative potential, periodontal ligament (PDL) and umbilical cord (UBC) tissues are an attractive potential mesenchymal stem cells (MSCs) source. This study compared the expression patterns of genes related to stemness between fresh PDL and UBC tissues. Materials and methods: PDL tissues were collected from 38 permanent premolars extracted for orthodontic purposes, and UBC tissues were obtained from three newborns. Each sample was immediately frozen to prevent RNA degradation. cDNA microarray analysis, quantitative real-time polymerase chain reaction (PCR), and immunohistochemical staining were performed. Gene expression patterns associated with dental stemness (DS) and induced pluripotent stemness (iPS) were compared between PDL and UBC tissues. Results: In the cDNA microarray analyses, the expressions of most iPS genes were greater in the PDL than in the UBC. Meanwhile, the expressions of most DS genes were greater in the UBC than in the PDL. Quantitative real-time PCR analyses showed that the expression levels of matrix metallopeptidase 13 (MMP13), ADAM metallopeptidase domain 22 (ADAM22), vascular cell adhesion protein 1 (VCAM1), and kruppel-like factor 4 (KLF4) genes were greater in the PDL than in the UBC, while the expressions of melanoma cell adhesion molecule (MCAM) and activated leukocyte cell adhesion molecule (ALCAM) were greater in the UBC than in the PDL. Conclusion: These results suggest that UBC and PDL tissues showed slightly different expression patterns of genes related to stemness, which warrants further investigation to use these tissues for future regeneration and implantation therapies.
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This study estimated long-term average ambient NO2 concentrations using TROPOspheric Monitoring Instrument (TROPOMI) tropospheric NO2 data and land use information at the spatial resolution of 500 m in California for the years 2018-2019. Our satellite-land use regression model demonstrated reasonably high predictive power with cross-validation (CV) R2 = 0.76, mean absolute error (MAE) = 1.95 ppb, and root mean squared error (RMSE) = 2.51 ppb in a comparison between measured and estimated NO2 concentrations. Exploiting the high-resolution NO2 estimates, we further investigated the representativeness of ground NO2 monitors for population exposures and examined the spatial variation of NO2 in relation to parcel-level property data for exposure attributions. The ground NO2 monitors were the most representative of population exposures in Los Angeles and San Diego counties, supported by population-weighted average NO2 concentrations (satellite-derived estimations) similar to arithmetic average NO2 concentrations (ground measurements). On the contrary, the exposure assessment using the ground monitors was the least representative and protective in Humboldt, San Luis Obispo, and Yolo counties with population-weighted average NO2 greater than arithmetic average NO2 by 82.2 % (1.85 ppb), 67.1 % (1.89 ppb), and 58.2 % (2.48 ppb), respectively. In a case study of LA County, we identified comparatively high NO2 concentrations for the property types of food processing facilities and high-density residential complexes (such as high-rise apartments and apartments). This finding provides evidence that these emerging sources may be crucial to mitigate cumulative NO2 exposures and subsequent health risks from a regulatory perspective.
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Poluentes Atmosféricos , Poluição do Ar , Dióxido de Nitrogênio/análise , Poluição do Ar/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental , Los Angeles , Material Particulado/análiseRESUMO
California experienced extreme and prolonged drought conditions during the early 2010s. To date, little is known regarding the influence of drought on air quality. Our study quantified site-specific associations between drought (defined by the Standardized Precipitation-Evapotranspiration Index; SPEI) and daily maximum 8-h ozone (O3) concentrations for California, USA, and then pooled these associations for the years 2009-2015. Overall, ambient O3 concentration was higher during droughts by 1.18 ppb (95% confidence interval (CI) = 1.00-1.36). The sensitivity of O3 to drought was greater during the warm season than during the cool season (1.73 ppb versus 0.79 ppb higher O3 during droughts) with substantial regional variation. In a pooled analysis with meteorological parameters as potential effect modifiers, the spatial heterogeneity of drought-O3 associations was explained strongly by average relative humidity for each season (71.9% (warm season) and 73.4% (cool season) of the drought-O3 associations explained), followed by the drought-related changes in relative humidity (47.6% (warm season)) and temperature (53.6% (cool season)). The pooled regression further identified regions susceptible for drought-related O3 increases as those with relatively low average relative humidity (10-25th percentiles or 44.3-47.3%) and larger drought-related decrease in relative humidity and increase in temperature. As the drought events are projected to occur with increased frequency and intensity in the era of climate change, the excess health burdens from O3 exposures attributed to the projected drought events need to be taken into account when allocating air quality and health resources. The impacts of O3 on health during droughts would confound the health burdens from the drought itself.
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Poluentes Atmosféricos , Poluição do Ar , Ozônio , Ozônio/análise , Secas , Poluentes Atmosféricos/análise , Poluição do Ar/análise , CaliforniaRESUMO
Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer, with a 10% five-year survival rate. However, little is known about its origin and the mechanisms governing its emergence. Our study characterized ADPC and NEPC in prostate tumors from 7 patients using scRNA-seq. First, we identified two NEPC gene expression signatures representing different phases of trans-differentiation. New marker genes we identified may be used for clinical diagnosis. Second, integrative analyses combining expression and subclonal architecture revealed different paths by which NEPC diverges from the original ADPC, either directly from treatment-naïve tumor cells or from specific intermediate states of treatment-resistance. Third, we inferred a hierarchical transcription factor (TF) network underlying the progression, which involves constitutive regulation by ASCL1, FOXA2, and selective regulation by NKX2-2, POU3F2, and SOX2. Together, these results defined the complex expression profiles and advanced our understanding of the genetic and transcriptomic mechanisms leading to NEPC differentiation.
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Transposable elements (TEs) encode regulatory elements that impact gene expression in multiple species, yet a comprehensive analysis of zebrafish TEs in the context of gene regulation is lacking. Here, we systematically investigate the epigenomic and transcriptomic landscape of TEs across 11 adult zebrafish tissues using multidimensional sequencing data. We find that TEs contribute substantially to a diverse array of regulatory elements in the zebrafish genome and that 37% of TEs are positioned in active regulatory states in adult zebrafish tissues. We identify TE subfamilies enriched in highly specific regulatory elements among different tissues. We use transcript assembly to discover TE-derived transcriptional units expressed across tissues. Finally, we show that novel TE-derived promoters can initiate tissue-specific transcription of alternate gene isoforms. This work provides a comprehensive profile of TE activity across normal zebrafish tissues, shedding light on mechanisms underlying the regulation of gene expression in this widely used model organism.
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Elementos de DNA Transponíveis , Epigenômica , Animais , Elementos de DNA Transponíveis/genética , Regiões Promotoras Genéticas , Sequências Reguladoras de Ácido Nucleico , Peixe-Zebra/genéticaRESUMO
A titanium-indium tin oxide (TITO) multilayer reflector was investigated to improve the light efficiency of high-power, near-infrared, light-emitting diodes (NIR-LEDs). The TITO/Ag was fabricated by combining a patterned TITO and an omnidirectional reflector (ODR). For fabricating a high-power NIR-LED, the wafer bond process required the TITO reflective structure, which has patterns filled by AlAu contact metal, bonded directly to the Ag reflector deposited on the silicon wafer. Among Ag-based single- and multilayer reflectors, the TITO/Ag showed the highest reflectance (R = 96%), which was favorable for wafer-bonded high-power NIR-LEDs. Therefore, the TITO/Ag reflector enabled the production of wafer-bonded NIR-LED chips that exhibit superior output performance (190 mW) compared with conventional cases using a single Ag reflector.
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Innate lymphocytes encompass a diverse array of phenotypic identities with specialized functions. DNA methylation and hydroxymethylation are essential for epigenetic fidelity and fate commitment. The landscapes of these modifications are unknown in innate lymphocytes. Here, we characterized the whole-genome distribution of methyl-CpG and 5-hydroxymethylcytosine (5hmC) in mouse innate lymphoid cell 3 (ILC3), ILC2 and natural killer (NK) cells. We identified differentially methylated regions (DMRs) and differentially hydroxymethylated regions (DHMRs) between ILC and NK cell subsets and correlated them with transcriptional signatures. We associated lineage-determining transcription factors (LDTFs) with demethylation and demonstrated unique patterns of DNA methylation/hydroxymethylation in relationship to open chromatin regions (OCRs), histone modifications and TF-binding sites. We further identified an association between hydroxymethylation and NK cell superenhancers (SEs). Using mice lacking the DNA hydroxymethylase TET2, we showed the requirement for TET2 in optimal production of hallmark cytokines by ILC3s and interleukin-17A (IL-17A) by inflammatory ILC2s. These findings provide a powerful resource for studying innate lymphocyte epigenetic regulation and decode the regulatory logic governing their identity.