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1.
Aquat Toxicol ; 271: 106928, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38688065

RESUMEN

The significant role of aquatic phytoplankton in global primary productivity, accounting for approximately 50 % on an annual basis, has been recognized as a crucial factor in the reduction of Hg(II). In this study, we compared the efficiency of Hg(II) photoreduction mediated by three types of algae leaching dissolved organic matter (DOM) and humic acid (DOM-HA). Especially, we investigated the potential effects of algae-leached DOM on the photoreduction of Hg(II) and its subsequent uptake by lettuce, which serves as an indicator of Hg bioavailability for aquatic plants. The results revealed that under light conditions, the conversion of Hg(II) to Hg(0) mediated by algae-leached DOM and DOM-HA was 6.4-39.9 % higher compared to dark condition. Furthermore, the free radical quenching experiment demonstrated that the reduction of Hg(II) mediated by DOM-HA was higher than algae-leached DOM, mainly due to its ability to generate superoxide anion (O2•-). Moreover, the photoreduction efficiences of Hg(II) mediated by algae-leached DOM were 29-18 % lower compared to DOM-HA. The FT-IR analysis revealed that the production of -SH from algae-leached DOM led to the formation of strong metal-complexes, which restricts the reduction process from Hg(II) to Hg(0). Finally, the hydroponics experiment demonstrated that algae-leached DOM inhibited the bioavailability of Hg(II) to plants more effectively than DOM-HA. Our research emphasizes the significant functional roles and potential mechanisms of algae in reducing Hg levels, thereby influencing the availability of Hg in aquatic ecosystems.


Asunto(s)
Sustancias Húmicas , Lactuca , Luz , Mercurio , Contaminantes Químicos del Agua , Lactuca/metabolismo , Lactuca/efectos de la radiación , Oxidación-Reducción
2.
Cancer Immunol Res ; 12(3): 350-362, 2024 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-38113030

RESUMEN

The existing T cell-centered immune checkpoint blockade therapies have been successful in treating some but not all patients with cancer. Immunosuppressive myeloid cells, including myeloid-derived suppressor cells (MDSC), that inhibit antitumor immunity and support multiple steps of tumor development are recognized as one of the major obstacles in cancer treatment. Leukocyte Ig-like receptor subfamily B3 (LILRB3), an immune inhibitory receptor containing tyrosine-based inhibitory motifs (ITIM), is expressed solely on myeloid cells. However, it is unknown whether LILRB3 is a critical checkpoint receptor in regulating the activity of immunosuppressive myeloid cells, and whether LILRB3 signaling can be blocked to activate the immune system to treat solid tumors. Here, we report that galectin-4 and galectin-7 induce activation of LILRB3 and that LILRB3 is functionally expressed on immunosuppressive myeloid cells. In some samples from patients with solid cancers, blockade of LILRB3 signaling by an antagonistic antibody inhibited the activity of immunosuppressive myeloid cells. Anti-LILRB3 also impeded tumor development in myeloid-specific LILRB3 transgenic mice through a T cell-dependent manner. LILRB3 blockade may prove to be a novel approach for immunotherapy of solid cancers.


Asunto(s)
Células Supresoras de Origen Mieloide , Neoplasias , Ratones , Animales , Humanos , Células Mieloides , Neoplasias/terapia , Linfocitos T , Receptores Inmunológicos , Microambiente Tumoral , Antígenos CD
3.
Ecotoxicol Environ Saf ; 266: 115585, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37856980

RESUMEN

Methylmercury is a neurotoxic compound that can enter rice fields through rainfall or irrigation with contaminated wastewater, and then contaminate the human food chain through the consumption of rice. Flooded paddy soil has a porous structure that facilitates air exchange with the atmosphere, but the presence of trace amounts of oxygen in flooded rice field soil and its impact on microbial-mediated formation of methylmercury is still unclear. We compared the microbial communities and their functions in oxygen-depleted and oxygen-limited paddy soil. We discovered that oxygen-limited paddy soil had higher methylmercury concentration, which was strongly correlated with soil properties and methylation potential. Compared with oxygen-depleted soil, oxygen-limited soil altered the microbial composition based on 16 S rRNA sequences, but not based on hgcA sequences. Moreover, oxygen-limited soil enhanced microbial activity significantly, increasing the abundance of more than half of the KEGG pathways, especially the metabolic pathways that might be involved in methylation. Our study unveils how microbial communities influence methylmercury formation in oxygen-limited paddy soil. ENVIRONMENTAL IMPLICATIONS: This study examined how low oxygen input affects microbial-induced MeHg formation in anaerobic paddy soil. We found that oxygen-limited soil produced more MeHg than oxygen-depleted soil. Oxygen input altered the microbial community structure of 16 S rRNA sequencing in anaerobic paddy soil, but had little impact on the hgcA sequencing community structure. Microbial activity and metabolic functions related to MeHg formation were also higher in oxygen-limited paddy soil. We suggest that oxygen may not be a limiting factor for Hg methylators, and that insufficient oxygen input in flooded paddy soil increases the risk of human exposure to MeHg from rice consumption.


Asunto(s)
Mercurio , Compuestos de Metilmercurio , Microbiota , Oryza , Contaminantes del Suelo , Humanos , Compuestos de Metilmercurio/metabolismo , Suelo/química , Oxígeno/metabolismo , Contaminantes del Suelo/análisis , Mercurio/análisis , Oryza/metabolismo
4.
Chemosphere ; 339: 139711, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37536532

RESUMEN

Straw amendment is a prevalent agricultural practice worldwide, which can reduce air pollution and improve soil fertility. However, the impact of aging straw amendment on the bioavailability of mercury (Hg) and methylmercury (MeHg) in paddy soil remains unclear. To investigate this, incubation experiments were conducted using the diffusive gradient in thin-film technique. Results showed that amendments of dry-wet aging (DRS), photochemical aging (LRS), and freeze-thaw aging rice straw (FRS) reduced the bioavailable MeHg in paddy soil by 2.2-27.6%, 13.5-69.8%, and 23.5-86.1%, respectively, compared to fresh rice straw (RS) amendment. This result could be due to changes in soil properties such as soil pH and overlying water Fe and Mn as well as microbial abundance (including Clostridiaceae, Firmicutes, and Actinobacteriota). Simultaneously, The LRS and FRS amendments reduced bioavailable Hg in paddy soil by 20.0-40.8% and 17.1-48.6%, respectively, while DRS increased the bioavailable Hg by 15.8-120.0%. This could be attributed to changes in soil oxidation-reduction potential and overlying water SO42- content. Additionally, the results of sand culture experiments showed that the concentrations of Hg uptake by rice seedlings were 97.1-118.2%, 28.1-35.6%, and 198.0-217.1% higher in dissolved organic matter (DOM) derived from DRS, LRS, and FRS than RS, indicating that aging straw leached DOM may promote the Hg bioavailable when straw amendment. This result could be due to lower molecular weight and higher CO functional group content. These results provide new insight into how aging straw amendment affects the bioavailability of Hg and MeHg in paddy soil under different climates.


Asunto(s)
Mercurio , Compuestos de Metilmercurio , Oryza , Contaminantes del Suelo , Compuestos de Metilmercurio/química , Mercurio/análisis , Suelo/química , Oryza/química , Disponibilidad Biológica , Contaminantes del Suelo/análisis
5.
J Hazard Mater ; 457: 131682, 2023 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-37270963

RESUMEN

The mechanisms by which eutrophication affects methylmercury (MeHg) production have not been comprehensively summarized, which hinders accurately predicting the MeHg risk in eutrophic lakes. In this review, we first discussed the effects of eutrophication on biogeochemical cycle of mercury (Hg). Special attentions were paid to the roles of algal organic matter (AOM) and iron (Fe)-sulfur (S)-phosphorus (P) dynamics in MeHg production. Finally, the suggestions for risk control of MeHg in eutrophic lakes were proposed. AOM can affect in situ Hg methylation by stimulating the abundance and activities of Hg methylating microorganisms and regulating Hg bioavailability, which are dependent on bacteria-strain and algae species, the molecular weight and composition of AOM as well as environmental conditions (e.g., light). Fe-S-P dynamics under eutrophication including sulfate reduction, FeS formation and P release could also play crucial but complicated roles in MeHg production, in which AOM may participate through influencing the dissolution and aggregation processes, structural order and surface properties of HgS nanoparticles (HgSNP). Future studies should pay more attention to the dynamics of AOM in responses to the changing environmental conditions (e.g., light penetration and redox fluctuations) and how such variations will subsequently affect MeHg production. The effects of Fe-S-P dynamics on MeHg production under eutrophication also deserve further investigations, especially the interactions between AOM and HgSNP. Remediation strategies with lower disturbance, greater stability and less cost like the technology of interfacial O2 nanobubbles are urgent to be explored. This review will deepen our understanding of the mechanisms of MeHg production in eutrophic lakes and provide theoretical guidance for its risk control.


Asunto(s)
Mercurio , Compuestos de Metilmercurio , Contaminantes Químicos del Agua , Compuestos de Metilmercurio/química , Lagos/química , Contaminantes Químicos del Agua/química , Mercurio/análisis , Bacterias
6.
Sci Total Environ ; 891: 164513, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37257614

RESUMEN

The transformation of Hg(II) and Hg(0) in aqueous systems governs the speciation and biogeochemical cycling of Hg. However, with the increasing amount of microplastics in the aqueous environment, little is known about the different effects of microplastic particles and their leached DOM on the photoreduction of Hg(II) to Hg(0) after long-term photoaging. In this study, we found that aged microplastic particles significantly inhibited the photoreduction efficiency (6.40-15.64 %) of Hg(II) compared to the control without any microplastic (31.02 %) and pristine microplastic particles (9.95-34.10 %). This inhibition was due to the adsorption of Hg by the microplastic particles, which decreased the amount of available Hg(II) (Hg(II)RED) that could participate in the photoreduction reaction. The characteristics of aged microplastic particles also indicated rougher surfaces and more oxygen-containing functional groups after photoaging, which may enhance their adsorption capacity compared to pristine microplastic. Interestingly, the photoreduction efficiency of Hg(II) was 11.58-53.28 % higher in the presence of microplastic leach DOM compared to the control. With increasing age, the microplastic leach DOM obviously promotes the photoreduction of Hg(II). Free radical inhibition and electron paramagnetic resonance spectra demonstrated that O2- in microplastic leach DOM contributed to the photoreduction of Hg(II) under light irradiation. Moreover, X-ray absorption near edge structure analyses demonstrated that microplastic leach DOM produced Hg(I) as the primary photoproduct, accounting for 43.17 % of the total Hg in the photoreaction solution and likely reducing it to Hg(0). This study provides novel insights into forecasting the synthesized risks of microplastic aging in the biogeochemical cycle of Hg within aqueous environments.

7.
Environ Res ; 231(Pt 1): 116127, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37187308

RESUMEN

Mercury (Hg) poses a significant risk in paddy fields, particularly when it is converted to methylmercury (MeHg) and accumulates in rice. However, the bioavailability and resupply kinetics of Hg in the paddy soil-water environment are not well understood. In this study, the diffusive gradients in thin films (DGT) and the 'DGT-induced fluxes in sediments' model (DIFS) were first adopted to investigate the Hg resupply kinetics, diffusion fluxes and bioavailability in a paddy environment subjected to flood-drain-reflood treatment and straw amendment. Our results show that although the straw amendment limited the bioavailability of Hg (38.2%-47.9% lower than control) in porewater by decreasing its resupply capacity, especially with smaller straw particles, the net production of MeHg in paddy fields was significantly increased after straw amendment (73.5%-77.9% higher than control). The results of microbial sequencing indicate that enhanced methylators (e.g., family Geobacter) and non-Hg methylators (e.g., Methanosarcinaceae) played a crucial role in MeHg production following straw amendment. Moreover, Hg-containing paddy soils generally tend to release Hg into the overlying water, while drain-reflood treatment changes the direction of Hg diffusion fluxes in the paddy soil-water interface. The drainage-reflooded treatment decreases the Hg reactive and resupply capacity of the paddy soil, thereby hindering the release of Hg from soil into overlying water during the early stages of reflooding. Overall, this study provides novel insights into the behavior of Hg in paddy soil-water surface microlayers.


Asunto(s)
Mercurio , Compuestos de Metilmercurio , Oryza , Contaminantes del Suelo , Suelo , Disponibilidad Biológica , Inundaciones , Contaminantes del Suelo/análisis , Mercurio/análisis
8.
PLoS One ; 18(4): e0278138, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37043427

RESUMEN

Directed greybox fuzzing guides fuzzers to explore specific objective code areas and has achieved good performance in some scenarios such as patch testing. However, if there are multiple objective code to explore, existing directed greybox fuzzers, such as AFLGo and Hawkeye, often neglect some targets because they use harmonic means of distance and prefers to test those targets with shorter reachable path. Besides, existing directed greybox fuzzers cannot calculate the accurate distance due to indirect calls in the program. In addition, existing directed greybox fuzzers fail to address the exploration and exploitation problem and have poor efficiency in seed scheduling. To address these problems, we propose a dynamic seed distance calculation scheme, it increase the seed distance dynamically when the reachable path encounter indirect call. Besides, the seed distance calculation can deal with the bias problem in multi-targets scenarios. With the seed distance calculation method, we propose a new seed scheduling algorithm based on the upper confidence bound algorithm to deal with the exploration and exploitation problem in drected greybox fuzzing. We implemented a prototype RLTG and evaluate it on real-world programs. Evaluation of our prototype shows that our approach outperforms a state-of-the-art directed fuzzer AFLGo. On the multi-targets benchmark Magma, RLTG reproduces bugs with 6.9x speedup and finds 66.7% more bugs than AFLGo.

9.
Chemosphere ; 327: 138437, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36963580

RESUMEN

The photochemical behavior of dissolved organic matter (DOM) in surface water and its effect on Hg(II) photoreduction has been extensively studied, but the contribution of DOM in paddy water to Hg(II) photoreduction is largely unknown. Herein, the effect of DOM from biochar (BCDOM), rice straw (RSDOM), and chicken manure (CMDOM) on Hg(II) photoreduction were examined. The comparable reduction efficiency of Hg(II) suggested that DOM-like fraction (62.3-63.7%) contributes more than suspended particulate matter-like fraction (17.7-23.4%) and bacteria-like fraction (13.0-20.0%) in paddy water. Under irradiation, the typical DOM significantly promoted Hg(II) photoreduction, and the reduction efficiency of BCDOM (65.5 ± 2.1%) was higher than that of CMDOM (48.3 ± 2.6%) and RSDOM (32.8 ± 2.4%) in 6 h. The quenching and kinetics experiments showed that superoxide anion (O2•-) was the main reactive species for Hg(II) photoreduction. Fluorescence spectroscopy and Fourier transform ion cyclotron resonance mass spectrometry revealed that DOM with a higher degree of lignin/carboxy-rich acyclic molecules, condensed aromatics structures, and phenolic compounds could promote the formation of O2•-. These findings highlight the importance of DOM in Hg(II) photoreduction and provide new ideas for regulating Hg cycling and bioavailability in paddy environments.


Asunto(s)
Materia Orgánica Disuelta , Mercurio , Mercurio/química , Disponibilidad Biológica , Cinética , Agua/química
10.
Artículo en Inglés | MEDLINE | ID: mdl-36834455

RESUMEN

Biochar can effectively reduce the phytoavailability of mercury (Hg) in soil, but the mechanisms are not fully understood. In this study, the dynamic changes in Hg content adsorbed by the biochar (BC-Hg), Hg phytoavailability in the soil (P-Hg), and soil dissolved organic matter (DOM) characteristics were determined over a 60-day treatment period. Biochar obtained at 300 °C, 500 °C and 700 °C reduced the P-Hg concentration assessed by MgCl2 extraction by 9.4%, 23.5% and 32.7%, respectively. However, biochar showed a very limited adsorption on Hg, with the maximum BC-Hg content only accounting for 1.1% of the total amount. High-resolution scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM-EDS) results showed that the proportion of Hg atoms in biochar after 60 d was barely detectable. Biochar treatment can shift soil DOM toward higher aromatic content and molecular weight. Additionally, the addition of high-temperature biochar increased more humus-like components, but low-temperature biochar increased more protein-like components. Correlation analysis and partial least squares path modeling (PLS-PM) showed that biochar promoted humus-like fractions formation to reduce the Hg phytoavailability. This research has deepened the understanding of the mechanisms by which biochar stabilizes Hg in agricultural soils.


Asunto(s)
Mercurio , Contaminantes del Suelo , Suelo/química , Materia Orgánica Disuelta , Carbón Orgánico/química , Mercurio/análisis , Contaminantes del Suelo/análisis
11.
Expert Rev Neurother ; 22(10): 875-888, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36242781

RESUMEN

BACKGROUND: This study aims to explore the treatment efficacy of different motor rehabilitation interventions for upper limb impairment recovery. RESEARCH DESIGN & METHODS: Publications were searched in PubMed and Embase. 4 grouped motor rehabilitation treatments (training, technological intervention, pharmacological intervention, and neuromodulation) were compared. The change of the Fugl-Meyer Assessment Scale for Upper Extremity (FMA-UE) was applied to assess upper limb function after stroke. RESULTS: 56 studies including 5292 patients were identified. A significant difference was found among the 4 groups (P = 0.02). Neuromodulation interventions had the best treatment efficacy among the 4 types of interventions (P < 0.01). Among neuromodulation interventions, acupuncture, electric, or magnetic intervention all had therapeutic efficacy for stroke upper limb recovery, without significant subgroup difference (P = 0.34). Stroke patients with mild upper limb impairment might not benefit from motor rehabilitation (P = 0.14). CONCLUSION: Neuromodulation interventions might have the best therapeutic efficacy among motor rehabilitation treatments for upper limb impairment after stroke. It is a potential treatment direction for upper limb recovery among stroke patients. However, since a large proportion of the original studies are low to very low-quality evidence, large-scale RCTs should be conducted in the future to validate current findings and assess treatment effects based on patient characteristics.


Asunto(s)
Accidente Cerebrovascular , Extremidad Superior , Humanos , Resultado del Tratamiento , Accidente Cerebrovascular/terapia
12.
Front Immunol ; 13: 996026, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36211388

RESUMEN

The current immune checkpoint blockade therapy has been successful in treating some cancers but not others. New molecular targets and therapeutic approaches of cancer immunology need to be identified. Leukocyte associated immunoglobulin like receptor 1 (LAIR1) is an immune inhibitory receptor expressing on most immune cell types. However, it remains a question whether we can specifically and actively block LAIR1 signaling to activate immune responses for cancer treatment. Here we report the development of specific antagonistic anti-LAIR1 monoclonal antibodies and studied the effects of LAIR1 blockade on the anti-tumor immune functions. The anti-LAIR1 antagonistic antibody stimulated the activities of T cells, natural killer cells, macrophages, and dendritic cells in vitro. The single-cell RNA sequencing analysis of intratumoral immune cells in syngeneic human LAIR1 transgenic mice treated with control or anti-LAIR1 antagonist antibodies indicates that LAIR1 signaling blockade increased the numbers of CD4 memory T cells and inflammatory macrophages, but decreased those of pro-tumor macrophages, regulatory T cells, and plasmacytoid dendritic cells. Importantly, the LAIR1 blockade by the antagonistic antibody inhibited the activity of immunosuppressive myeloid cells and reactivated T cells from cancer patients in vitro and impeded tumor metastasis in a humanized mouse model. Blocking LAIR1 signaling in immune cells represents a promising strategy for development of anti-cancer immunotherapy.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Neoplasias , Animales , Anticuerpos Monoclonales/uso terapéutico , Humanos , Inmunoterapia , Ratones , Linfocitos T Reguladores
13.
Contrast Media Mol Imaging ; 2022: 1225253, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35965622

RESUMEN

Transcutaneous electrical acupoint stimulation (TEAS) is a noninvasive and therapeutic technique that stimulated the acupoint by delivering electricity. Whether TEAS could relieve cancer-related fatigue (CRF), anxiety, and depression and improve the quality of life in cancer patients remains controversial. Thus, we conducted a thorough literature search of electronic Chinese and English databases for randomized controlled trials (RCTs) reporting the effect of CRF, anxiety, depression, and quality of life in cancer patients from inception to July 1st, 2021. The Cochrane Collaboration Risk of Bias criteria were used to assess the risk of bias for each included RCT. Continuous variables were analyzed using standardized mean difference (SMD) and 95% confidence interval (CI). A fixed-effects model was used for the meta-analysis of all outcomes. A total of nine RCTs with 924 cancer patients were included in this analysis, including 460 patients in the interventional group and 464 patients in the control group. We found that TEAS could significantly reduce CRF, depression, and anxiety (SWD = -0.83, 95% CI: -0.99 to -0.66, P < 0.05) and improve the quality of life (SWD = -1.37, 95% CI: -2.34 to -0.40, P < 0.05). The funnel plot analysis revealed no significant publication bias. We conclude that TEAS is beneficial for reducing CRF, depression, and anxiety and improving the quality of life of cancer patients, but additional high-quality evidence in the future is entailed to support this.


Asunto(s)
Puntos de Acupuntura , Neoplasias , Ansiedad/etiología , Ansiedad/terapia , Estimulación Eléctrica , Fatiga/etiología , Fatiga/terapia , Humanos , Neoplasias/complicaciones , Neoplasias/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto
14.
PLoS One ; 17(1): e0262176, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35073360

RESUMEN

Transport layer security (TLS) protocol is the most widely used security protocol in modern network communications. However, protocol vulnerabilities caused by the design of the network protocol or its implementation by programmers emerge one after another. Meanwhile, various versions of TLS protocol implementations exhibit different behavioral characteristics. Researchers are attempting to find the differences in protocol implementations based on differential testing, which is conducive to discovering the vulnerabilities. This paper provides a solution to find the differences more efficiently by targeting the TLS protocol handshake process. The differences of different implementations during the fuzzing process, such as code coverage and response data, are taken to guide the mutation of test cases, and the seeds are mutated based on the TLS protocol syntax. In addition, the definition of duplicate discrepancies is theoretically explored to investigate the root cause of the discrepancies and to reduce the number of duplicate cases that are caused by the same reason. Besides, the necessary conditions for excluding duplicate cases are further analyzed to develop the deduplication strategy. The proposed method is developed based on open-source tools, i.e., NEZHA and TLS-diff. Three types of widely used TLS protocol implementations, i.e., OpenSSL, BoringSSL, and LibreSSL, are taken for experimental testing. The experimental results show that the proposed method can effectively improve the ability to find differences between different implementations. Under the same test scale or the same time, the amount of discrepancies increases by about 20% compared to TLS-diff, indicating the effectiveness of the deduplication strategy.


Asunto(s)
Seguridad Computacional , Algoritmos , Lógica Difusa , Programas Informáticos
15.
Antib Ther ; 4(1): 16-33, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33928233

RESUMEN

Inhibitory leukocyte immunoglobulin-like receptors (LILRBs 1-5) transduce signals via intracellular immunoreceptor tyrosine-based inhibitory motifs that recruit phosphatases to negatively regulate immune activation. The activation of LILRB signaling in immune cells may contribute to immune evasion. In addition, the expression and signaling of LILRBs in cancer cells especially in certain hematologic malignant cells directly support cancer development. Certain LILRBs thus have dual roles in cancer biology-as immune checkpoint molecules and tumor-supporting factors. Here, we review the expression, ligands, signaling, and functions of LILRBs, as well as therapeutic development targeting them. LILRBs may represent attractive targets for cancer treatment, and antagonizing LILRB signaling may prove to be effective anti-cancer strategies.

16.
Mol Cell ; 67(2): 203-213.e4, 2017 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-28648778

RESUMEN

Although the coupling between circadian and cell cycles allows circadian clocks to gate cell division and DNA replication in many organisms, circadian clocks were thought to function independently of cell cycle. Here, we show that DNA replication is required for circadian clock function in Neurospora. Genetic and pharmacological inhibition of DNA replication abolished both overt and molecular rhythmicities by repressing frequency (frq) gene transcription. DNA replication is essential for the rhythmic changes of nucleosome composition at the frq promoter. The FACT complex, known to be involved in histone disassembly/reassembly, is required for clock function and is recruited to the frq promoter in a replication-dependent manner to promote replacement of histone H2A.Z by H2A. Finally, deletion of H2A.Z uncoupled the dependence of the circadian clock on DNA replication. Together, these results establish circadian clock and cell cycle as interdependent coupled oscillators and identify DNA replication as a critical process in the circadian mechanism.


Asunto(s)
Relojes Circadianos , Ritmo Circadiano , Replicación del ADN , ADN de Hongos/metabolismo , Neurospora/metabolismo , Nucleosomas/metabolismo , Animales , ADN de Hongos/química , ADN de Hongos/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulación Fúngica de la Expresión Génica , Proteínas del Grupo de Alta Movilidad/genética , Proteínas del Grupo de Alta Movilidad/metabolismo , Histonas/genética , Histonas/metabolismo , Neurospora/genética , Conformación de Ácido Nucleico , Nucleosomas/química , Nucleosomas/genética , Antígeno Nuclear de Célula en Proliferación/genética , Antígeno Nuclear de Célula en Proliferación/metabolismo , Regiones Promotoras Genéticas , Conformación Proteica , Relación Estructura-Actividad , Factores de Tiempo , Transcripción Genética , Factores de Elongación Transcripcional/genética , Factores de Elongación Transcripcional/metabolismo
17.
Chin Med J (Engl) ; 129(7): 799-803, 2016 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-26996474

RESUMEN

BACKGROUND: Determining the nerve of origin for vestibular schwannoma (VS), as a method for predicting hearing prognosis, has not been systematically considered. The vestibular test can be used to investigate the function of the superior vestibular nerve (SVN) and the inferior vestibular nerve (IVN). This study aimed to preoperatively distinguish the nerve of origin for VS patients using the vestibular test, and determine if this correlated with hearing preservation. METHODS: A total of 106 patients with unilateral VS were enrolled in this study prospectively. Each patient received a caloric test, vestibular-evoked myogenic potential (VEMP) test, and cochlear nerve function test (hearing) before the operation and 1 week, 3, and 6 months, postoperatively. All patients underwent surgical removal of the VS using the suboccipital approach. During the operation, the nerve of tumor origin (SVN or IVN) was identified by the surgeon. Tumor size was measured by preoperative magnetic resonance imaging. RESULTS: The nerve of tumor origin could not be unequivocally identified in 38 patients (38/106, 35.80%). These patients were not subsequently evaluated. In 26 patients (nine females, seventeen males), tumors arose from the SVN and in 42 patients (18 females, 24 males), tumors arose from the IVN. Comparing with the nerve of origins (SVN and IVN) of tumors, the results of the caloric tests and VEMP tests were significantly different in tumors originating from the SVN and the IVN in our study. Hearing was preserved in 16 of 26 patients (61.54%) with SVN-originating tumors, whereas hearing was preserved in only seven of 42 patients (16.67%) with IVN-originating tumors. CONCLUSIONS: Our data suggest that caloric and VEMP tests might help to identify whether VS tumors originate from the SVN or IVN. These tests could also be used to evaluate the residual function of the nerves after surgery. Using this information, we might better predict the preservation of hearing for patients.


Asunto(s)
Audición , Neuroma Acústico/fisiopatología , Nervio Vestibular/fisiología , Adulto , Femenino , Humanos , Masculino , Neuroma Acústico/patología
18.
Nucleic Acids Res ; 42(10): 6183-95, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24711369

RESUMEN

In Neurospora crassa, the methionine synthase gene met-8 plays a key role in methionine synthesis. In this study, we found that MET-8 protein levels were compromised in several mutants defective in proper heterochromatin formation. Bioinformatics analysis revealed a 50-kb AT-rich region adjacent to the met-8 promoter. ChIP assays confirmed that trimethylated H3K9 was enriched in this region, indicating that heterochromatin may form upstream of met-8. In an H3K9R mutant strain, the output of met-8 was dramatically reduced, similar to what we observed in mutant strains that had defective heterochromatin formation. Furthermore, the production of ectopically expressed met-8 at the his-3 locus in the absence of a normal heterochromatin environment was inefficient, whereas ectopic expression of met-8 downstream of two other heterochromatin domains was efficient. In addition, our data show that the expression of mig-6 was also controlled by an upstream 4.2-kb AT-rich region similar to that of the met-8 gene, and we demonstrate that the AT-rich regions adjacent to met-8 or mig-6 are required for their peak expression. Our study indicates that met-8 and mig-6 may represent a novel type of gene, whose expression relies on the proper formation of a nearby heterochromatin region.


Asunto(s)
5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa/genética , Proteínas Fúngicas/genética , Regulación Fúngica de la Expresión Génica , Heterocromatina/metabolismo , Neurospora crassa/genética , Regiones no Traducidas 5' , 5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa/metabolismo , Proteínas Fúngicas/metabolismo , Eliminación de Gen , Histona Metiltransferasas , N-Metiltransferasa de Histona-Lisina/genética , Histonas/metabolismo , Neurospora crassa/enzimología , Neurospora crassa/metabolismo , ARN Polimerasa II/metabolismo
19.
Zhongguo Zhong Yao Za Zhi ; 32(8): 664-7, 2007 Apr.
Artículo en Chino | MEDLINE | ID: mdl-17608213

RESUMEN

OBJECTIVE: To study viruses infecting Pinellia ternata in China. METHOD: Symptom observation, DAS-ELISA and RT-PCR detection were applied. RESULT AND CONCLUSION: During a survey in early spring, SMV and CMV were both commonly distributed as main viruses infecting P. ternata collected from different areas in China. But DsMV was the virus which infected P. ternate in natural condition. The infection ratio of cultivated P. ternate by SMV and CMV were 71.4% and 14.3% respectively for 21 samples collected from Ningbo, Zhejiang province; 100% and 44.4% for 18 samples from Xiaoshan, Zhejiang province; 61.9% and 33.3% for 21 samples from Hebei province; 50.0% and 41.7% for 12 samples from Anhui province; 16.7% and 16.7% for 12 samples from Sichuan province; 31.3% and none for 16 samples from Beijing. And the infection ratio of 25 wild samples from different areas of China infected by SMV and CMV were both 20.0%.


Asunto(s)
Cucumovirus/aislamiento & purificación , Virus del Mosaico/aislamiento & purificación , Pinellia/virología , Plantas Medicinales/virología , China , Análisis por Conglomerados , Cucumovirus/genética , ADN Complementario/química , ADN Complementario/genética , Virus del Mosaico/clasificación , Virus del Mosaico/genética , Enfermedades de las Plantas/virología , Análisis de Secuencia de ADN
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