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Glass transition, commonly manifested upon cooling a liquid, is continuous and cooling rate dependent. For decades, the thermodynamic basis in liquid-glass transition has been at the center of debate. Here, long-time isothermal annealing was conducted via molecular dynamics simulations for metallic glasses to explore the connection of physical aging in supercooled liquid and glassy states. An anomalous two-step aging is observed in various metallic glasses, exhibiting features of supercooled liquid dynamics in the first step and glassy dynamics in the second step, respectively. Furthermore, the transition potential energy is independent of initial states, proving that it is intrinsic for a metallic glass at a given temperature. We propose that the observed dynamic transition from supercooled liquid dynamics to glassy dynamics could be glass transition manifested isothermally. On this basis, glass transition is no longer cooling rate dependent, but is shown as a clear phase boundary in the temperature-energy phase diagram. Hence, a modified out-of-equilibrium phase diagram is proposed, providing new insights into the nature of glass transition.
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During meiotic prophase, cohesin-dependent axial structures are formed in the synaptonemal complex (SC). However, the functional correlation between these structures and cohesion remains elusive. Here, we examined the formation of cohesin-dependent axial structures in the fission yeast Schizosaccharomyces pombe. This organism forms atypical SCs composed of linear elements (LinEs) resembling the lateral elements of SC but lacking the transverse filaments. Hi-C analysis using a highly synchronous population of meiotic S. pombe cells revealed that the axis-loop chromatin structure formed in meiotic prophase was dependent on the Rec8 cohesin complex. In contrast, the Rec8-mediated formation of the axis-loop structure occurred in cells lacking components of LinEs. To dissect the functions of Rec8, we identified a rec8-F204S mutant that lost the ability to assemble the axis-loop structure without losing cohesion of sister chromatids. This mutant showed defects in the formation of the axis-loop structure and LinE assembly and thus exhibited reduced meiotic recombination. Collectively, our results demonstrate that the Rec8-dependent axis-loop structure provides a structural platform essential for LinE assembly, facilitating meiotic recombination of homologous chromosomes, independently of its role in sister chromatid cohesion.
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Meiosis , Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Proteínas de Ciclo Celular , Cromatina , Proteínas Cromosómicas no Histona , Fosfoproteínas/genética , Schizosaccharomyces/citología , Schizosaccharomyces/genética , Proteínas de Schizosaccharomyces pombe/genética , Complejo Sinaptonémico , CohesinasRESUMEN
Nitrogen fertilizer supports agricultural intensification, but its manufacturing results in substantial contaminated sites. Ammonia nitrogen is the main specific pollutant in retired nitrogen fertilizer sites with potential human health and odor risks. However, few studies focus on ammonia nitrogen risk assessment at contaminated sites, particularly considering its solid-liquid partitioning process (Kd) and ammonium/ammonia equilibrium process (R) in the soil. This study took a closed nitrogen fertilizer factory site as an example and innovatively introduced Kd and R to scientifically assess the human health and odor risk of ammonia nitrogen. The risk control values (RCVs) of ammonia nitrogen based on human health and odor risk were also derived. The maximum concentration of ammonia nitrogen was 3380â¯mg/kg in the unsaturated soil, which was acceptable for human health because the health RCVs were 5589 â¼ 137,471â¯mg/kg in various scenarios. However, odor risk was unacceptable for RCVs were 296 â¼ 1111â¯mg/kg under excavation scenarios and 1118 â¼ 35,979â¯mg/kg under non-excavation scenarios. Of particular concern, introducing Kd and R in calculation increased the human health and odor RCVs by up to 27.92 times. Despite the advancements in ammonia risk assessment due to the introduction of Kd and R, odor risk during excavation remains a vital issue. These findings inform a more scientific assessment of soil ammonia risk at contaminated sites and provide valuable insights for the management and redevelopment of abandoned nitrogen fertilizer plant sites.
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Amoníaco , Compuestos de Amonio , Humanos , Amoníaco/análisis , Suelo , Nitrógeno/análisis , Fertilizantes/análisis , Odorantes , Agricultura/métodos , ChinaRESUMEN
The quantum transport properties of defective two-dimensional (2D) GeP semiconductor nanodevice consisting of typical point defects, such as antisite defect, substitutional defect, and Schottky defect, have been studied by using density functional theory combined with non-equilibrium Green's function calculation. The antisite defect has indistinctive influences on electron transport. However, both substitutional and Schottky defect have introduced promising defect state at the Fermi level, indicating the possibility of improvement on the carrier transport. Our quantitative quantum transport calculations ofI-Vbbehavior have revealed that the electrical characters are enhanced. Moreover, the P atom vacancy could induce significant negative differential resistance phenomenon, and the physical mechanism is unveiled by detailed analysis. The transfer characteristic properties could be prominently improved by substitutional defect and vacancy defect. Most importantly, we have proposed a computational design of GeP-based electronic device with improved electrical performance by introducing vacancy defect. Our findings could be helpful to the practical application of novel 2D GeP semiconductor nanodevice in future.
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Renal tubulointerstitial fibrosis (TIF) is considered as the final convergent pathway of diabetic nephropathy (DN) without effective therapies currently. MiRNAs play a key role in fibrotic diseases and become promising therapeutic targets for kidney diseases, while miRNA clusters, formed by the cluster arrangement of miRNAs on chromosomes, can regulate diverse biological functions alone or synergistically. In this study, we developed clustered miR-23a/27a/26a-loaded skeletal muscle satellite cells-derived exosomes (Exos) engineered with RVG peptide, and investigated their therapeutic efficacy in a murine model of DN. Firstly, we showed that miR-23a-3p, miR-26a-5p and miR-27a-3p were markedly decreased in serum samples of DN patients using miRNA sequencing. Meanwhile, we confirmed that miR-23a-3p, miR-26a-5p and miR-27a-3p were primarily located in proximal renal tubules and highly negatively correlated with TIF in db/db mice at 20 weeks of age. We then engineered RVG-miR-23a/27a/26a cluster loaded Exos derived from muscle satellite cells, which not only enhanced the stability of miR-23a/27a/26a cluster, but also efficiently delivered more miR-23a/27a/26a cluster homing to the injured kidney. More importantly, administration of RVG-miR-23a/27a/26a-Exos (100 µg, i.v., once a week for 8 weeks) significantly ameliorated tubular injury and TIF in db/db mice at 20 weeks of age. We revealed that miR-23a/27a/26a-Exos enhanced antifibrotic effects by repressing miRNA cluster-targeting Lpp simultaneously, as well as miR-27a-3p-targeting Zbtb20 and miR-26a-5p-targeting Klhl42, respectively. Knockdown of Lpp by injection of AAV-Lpp-RNAi effectively ameliorated the progression of TIF in DN mice. Taken together, we established a novel kidney-targeting Exo-based delivery system by manipulating the miRNA-23a/27a/26a cluster to ameliorate TIF in DN, thus providing a promising therapeutic strategy for DN.
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Nefropatías Diabéticas , Exosomas , MicroARNs , Células Satélite del Músculo Esquelético , Animales , Humanos , Ratones , Diabetes Mellitus/terapia , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/patología , Nefropatías Diabéticas/terapia , Exosomas/metabolismo , Fibrosis , MicroARNs/metabolismo , MicroARNs/farmacología , MicroARNs/uso terapéutico , Células Satélite del Músculo Esquelético/metabolismo , Complicaciones de la Diabetes/terapiaRESUMEN
With the development of the economy and the adjustment of urban planning and layout, abandoned pesticide sites are widely distributed in major and medium cities in China. Groundwater pollution of a large number of abandoned pesticide-contaminated sites has caused great potential risks to human health. Up to now, few relevant studies concerned the spatiotemporal variation of risks exposure to multi-pollutants in groundwater using probabilistic methods. In our study, the spatiotemporal characteristics of organics contamination and corresponding health risks in the groundwater of a closed pesticide site were systematically assessed. A total of 152 pollutants were targeted for monitoring over a time span up to five years (i.e., June 2016-June 2020). BTEX, phenols, chlorinated aliphatic hydrocarbons, and chlorinated aromatic hydrocarbons were the main contaminants. The metadata was subjected to health risk assessments using the deterministic and probabilistic methods for four age groups, and the results showed that the risks were highly unacceptable. Both methods showed that children (0-5 years old) and adults (19-70 years old) were the age groups with the highest carcinogenic and non-carcinogenic risks, respectively. Compared with inhalation and dermal contact, oral ingestion was the predominant exposure pathway that contributed 98.41%-99.69% of overall health risks. Spatiotemporal analysis further revealed that the overall risks first increased then decreased within five years. The risk contributions of different pollutants were also found to vary substantially with time, indicating that dynamic risk assessment is necessary. Compared with the probabilistic method, the deterministic approach relatively overestimated the true risks of OPs. The results provide a scientific basis and practical experience for scientific management and governance of abandoned pesticide sites.
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Contaminantes Ambientales , Agua Subterránea , Hidrocarburos Clorados , Plaguicidas , Contaminantes Químicos del Agua , Niño , Adulto , Humanos , Recién Nacido , Lactante , Preescolar , Adulto Joven , Persona de Mediana Edad , Anciano , Plaguicidas/análisis , Solventes , Contaminantes Químicos del Agua/análisis , Hidrocarburos Clorados/análisis , Medición de Riesgo , China , Monitoreo del AmbienteRESUMEN
The structure of chromosomes dramatically changes upon entering meiosis to ensure the successful progression of meiosis-specific events. During this process, a multilayer proteinaceous structure called a synaptonemal complex (SC) is formed in many eukaryotes. However, in the fission yeast Schizosaccharomyces pombe, linear elements (LinEs), which are structures related to axial elements of the SC, form on the meiotic cohesin-based chromosome axis. The structure of LinEs has been observed using silver-stained electron micrographs or in immunofluorescence-stained spread nuclei. However, the fine structure of LinEs and their dynamics in intact living cells remain to be elucidated. In this study, we performed live cell imaging with wide-field fluorescence microscopy as well as 3D structured illumination microscopy (3D-SIM) of the core components of LinEs (Rec10, Rec25, Rec27, Mug20) and a linE-binding protein Hop1. We found that LinEs form along the chromosome axis and elongate during meiotic prophase. 3D-SIM microscopy revealed that Rec10 localized to meiotic chromosomes in the absence of other LinE proteins, but shaped into LinEs only in the presence of all three other components, the Rec25, Rec27, and Mug20. Elongation of LinEs was impaired in double-strand break-defective rec12- cells. The structure of LinEs persisted after treatment with 1,6-hexanediol and showed slow fluorescence recovery from photobleaching. These results indicate that LinEs are stable structures resembling axial elements of the SC.
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Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Proteínas de Ciclo Celular/metabolismo , Proteínas de Unión al ADN/metabolismo , Meiosis , Proteínas Nucleares/metabolismo , Profase , Schizosaccharomyces/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , Proteínas de Schizosaccharomyces pombe/metabolismo , Complejo Sinaptonémico/metabolismoRESUMEN
Pulmonary fibrosis is a progressive interstitial lung disease with poor prognosis. Anemarrhenae Rhizoma is a traditional Chinese herbal medicine and has been applied in clinical practice for a long history. Recently, components of Anemarrhenae Rhizoma were reported to possess anti-inflammatory and immunomodulatory features; however, the effect of them on pulmonary fibrosis remains unknown. In this study, we explored the therapeutic effect of total extract of Anemarrhenae Rhizoma (TEAR) on bleomycin-induced pulmonary fibrosis. Pulmonary fibrosis rat model was established by a single intratracheal instillation of bleomycin, three doses of TEAR were intragastrically administered for consecutive 28 days. Subsequent to sacrificing of rats, pulmonary fibrosis was observed in rats treated with bleomycin, but administration of TEAR attenuated lung fibrosis, as evidenced by the improved lung histopathological damage and decreased weight loss and lung index. Moreover, TEAR treatment inhibited the inflammatory response in lung fibrosis, which was shown by the reduced nitrogen oxide level and myeloperoxidase activity. Furthermore, TEAR modulated the redox balance in lung tissue by alleviated lipid peroxidation and enhanced enzymatic antioxidants activity. Meanwhile, TEAR protected the rats from fibrosis in a dose-dependent manner, and the anti-fibrotic activity of TEAR may be related to the modulation of TGF-ß1/Smad signaling pathway. Collectively, TEAR alleviates bleomycin-induced pulmonary fibrosis, indicating perspectives for development of a potential agent for lung fibrosis therapy.
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Anemarrhena/química , Medicamentos Herbarios Chinos/uso terapéutico , Flavonoides/uso terapéutico , Fibrosis Pulmonar/tratamiento farmacológico , Rizoma/química , Saponinas/uso terapéutico , Animales , Bleomicina , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Flavonoides/química , Flavonoides/aislamiento & purificación , Masculino , Medicina Tradicional China , Estructura Molecular , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/patología , Ratas , Ratas Sprague-Dawley , Saponinas/química , Saponinas/aislamiento & purificación , Relación Estructura-ActividadRESUMEN
Strontium (Sr) is an alkaline earth metal that has adverse effects on bone tissue, but received little attention compared to other often-studied metals. This study analyzed the contents/concentrations of Sr, barium (Ba), sulfate (SO42-), sulfide (S2-), and six common metals in 209 multi-media samples, including slag, soil, groundwater, surface water, and sediment, collected at a large Sr slag pile area. Sr was the dominant chemical of concern (COC) in the soil and groundwater, with contents/concentrations being 35.50-32200 mg/kg and 0.57-152 mg/L, respectively, much higher than those reported in previous research. Contents/concentrations of all COCs in the surface water and sediment were relatively low, except Sr content in the sediment near the slag pile. The LogKd value of Sr was calculated to be lower than those of common metals, indicating relatively high mobility of Sr in the aquatic environment. Contamination assessment using Nemerow index indicated near half of the soil and groundwater sampling locations, especially those within and near the slag pile, were heavily contaminated, and Sr was the dominant COC. The positive matrix factorization model suggested four sources for the COCs in soil, including Sr slag pile/SrCO3 production, agricultural activities, industrial activities, and natural sources, with contribution rates of 66.88%, 5.28%, 7.5%, and 20.34%, respectively. Monte Carlo simulation-based probabilistic health risk assessment revealed that the non-carcinogenic risk of groundwater, and the carcinogenic risk of soil and groundwater, were unacceptable. Notably, Sr was the unique COC posing non-carcinogenic risk among the COCs studied. Our results provide the scientific support needed for managing Sr point source impacted area.
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Metales Pesados , Contaminantes del Suelo , China , Monitoreo del Ambiente , Metales Pesados/análisis , Medición de Riesgo , Suelo , Contaminantes del Suelo/análisis , Estroncio , AguaRESUMEN
Meiotic recombination is initiated by programmed formation of DNA double strand breaks (DSBs), which are mainly formed at recombination hotspots. Meiotic DSBs require multiple proteins including the conserved protein Spo11 and its cofactors, and are influenced by chromatin structure. For example, local chromatin around hotspots directly impacts DSB formation. Moreover, DSB is proposed to occur in a higher-order chromatin architecture termed 'axis-loop', in which many loops protrude from cohesin-enriched axis. However, still much remains unknown about how meiotic DSBs are generated in chromatin. Here, we show that the conserved histone H2A variant H2A.Z promotes meiotic DSB formation in fission yeast. Detailed investigation revealed that H2A.Z is neither enriched around hotspots nor axis sites, and that transcript levels of DSB-promoting factors were maintained without H2A.Z. Moreover, H2A.Z appeared to be dispensable for chromatin binding of meiotic cohesin. Instead, in H2A.Z-lacking mutants, multiple proteins involved in DSB formation, such as the fission yeast Spo11 homolog and its regulators, were less associated with chromatin. Remarkably, nuclei were more compact in the absence of H2A.Z. Based on these, we propose that fission yeast H2A.Z promotes meiotic DSB formation partly through modulating chromosome architecture to enhance interaction between DSB-related proteins and cohesin-loaded chromatin.
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Roturas del ADN de Doble Cadena , ADN de Hongos/metabolismo , Histonas/metabolismo , Reparación del ADN por Recombinación , Proteínas de Schizosaccharomyces pombe/metabolismo , Cromatina/genética , Cromatina/metabolismo , Cromosomas Fúngicos/genética , Cromosomas Fúngicos/metabolismo , ADN de Hongos/genética , Endodesoxirribonucleasas/genética , Endodesoxirribonucleasas/metabolismo , Histonas/genética , Recombinación Homóloga , Meiosis/genética , Schizosaccharomyces/genética , Schizosaccharomyces/metabolismo , Proteínas de Schizosaccharomyces pombe/genéticaRESUMEN
Meiotic recombination ensures faithful chromosome segregation and confers genetic diversity to gametes, and thus, is a key DNA-templated reaction not only for sexual reproduction, but also evolution. This recombination is initiated by programmed DNA double strand breaks (DSBs), which are mainly formed at recombination hotspots. As meiotic DSB formation requires multiple proteins, it is regulated by chromatin structure. In particular, DSB occurs in a higher-order chromatin architecture termed "axis-loop", in which many loops protrude from proteinaceous axis. Previous studies have suggested that assembly of this structure is dependent on chromatin binding of cohesin, which in turn recruits proteins implicated in DSB formation. However, roles of chromatin in meiotic DSB formation are not fully characterized. This review article summarizes our recent report showing that the conserved histone H2A variant H2A.Z promotes meiotic DSB formation in fission yeast. Through a series of experiments, we found that, in H2A.Z-lacking mutants, multiple proteins involved in DSB formation, but not cohesin subunits, are less associated with chromatin. Strikingly, nuclei were more compact in the absence of H2A.Z. These observations led us to propose that fission yeast H2A.Z promotes meiotic DSB formation partly through modulating chromosome architecture to enhance interaction between DSB-related proteins and cohesin-loaded chromatin. In addition, biological implications of our findings are discussed, and their relevance to DSB formation in other species as well as to other DNA-related events are also provided.
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Histonas/genética , Meiosis/genética , Recombinación Genética , Cromosomas Fúngicos , Roturas del ADN de Doble Cadena , ADN de Hongos/genética , Schizosaccharomyces/genética , Proteínas de Schizosaccharomyces pombe/genéticaRESUMEN
BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare malignant sarcoma with poor prognosis due to lack of effective treatments. Apatinib is a new potent oral small-molecule tyrosine kinase inhibitor, and targets the intracellular domain of vascular endothelial growth factor receptor 2 (VEGFR-2). In this study, we presented a case of intra-abdominal DSRCT which was effectively treated by apatinib. CASE PRESENTATION: A 32-year-old man was admitted due to increasing urination frequency and palpable mass in right lower abdomen for 2 months. The mass was resected and diagnosed DSRCT. The patient refused chemotherapy and radiotherapy,and used Chinese medicine only. Six months after the surgery, the patient re-hospitalized due to growing abdominal mass and ascites. Intraperitoneal cisplatin treatment showed little effect. Apatinib was then recommended. Apatinib revealed outstanding effect on reducing mass size and ascites during 2-month treatment. Apatinib therapy continued for additional 2 months, and the patient was in good condition. The only toxicity was hand-food syndrome, which was controllable and well tolerated. CONCLUSION: It is the first report that apatinib is effective on DSRCT. This report may provide an additional option for the treatment of metastatic DSRCT.
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Antineoplásicos/uso terapéutico , Tumor Desmoplásico de Células Pequeñas Redondas/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Piridinas/uso terapéutico , Adulto , Antineoplásicos/farmacología , Biopsia , Tumor Desmoplásico de Células Pequeñas Redondas/diagnóstico , Tumor Desmoplásico de Células Pequeñas Redondas/metabolismo , Humanos , Inmunohistoquímica , Imagen por Resonancia Magnética , Terapia Molecular Dirigida , Inhibidores de Proteínas Quinasas/farmacología , Piridinas/farmacología , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Little research has been carried out for the per- and polyfluoroalkyl substances (PFASs) in groundwater from non-industrial areas, even though it has been proved that PFASs can transport for long distance. In this study, the concentration profiles and geographical distribution of 14 PFASs, including two alternatives of perfluorooctane sulfonate (PFOS), 6:2 fluorotelomer sulfonate (6:2 FTS) and potassium 9-chlorohexadecafluoro-3-oxanonane-1-sulfonate (F-53B), were analyzed in groundwater samples (n = 102) collected from water wells in non-industrial areas. The total concentrations of PFASs (Σ14PFASs) in groundwater samples ranged from 2.69 to 556â¯ng/L (mean 43.1â¯ng/L). The detection rates of shorter chain (C4-C9) PFASs were 62.75-100%, higher than those of long chain (> C10) PFASs with detection rates of less than 40%. The source identification using hierarchical cluster analysis and Spearman rank correlation analysis suggested that domestic sewage and atmospheric deposition may contribute significantly to the PFAS occurrence in groundwater in non-industrial areas, while the nearby industrial parks may contribute some, but not at a significant level. Furthermore, the human health risk assessment analysis shows that the health hazards associated with perfluorooctanoic acid (PFOA) and PFOS, two of the main PFAS constituents in groundwater from non-industrial areas, were one or two orders of magnitude higher than those in a previous study, but were unlikely to cause long-term harm to the residents via the drinking water exposure pathway alone.
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Ácidos Alcanesulfónicos/análisis , Caprilatos/análisis , Monitoreo del Ambiente/métodos , Fluorocarburos/análisis , Agua Subterránea/química , Contaminantes Químicos del Agua/análisis , Ácidos Alcanesulfónicos/química , Caprilatos/química , China , Agua Potable/análisis , Fluorocarburos/química , Humanos , Medición de Riesgo , Estaciones del Año , Aguas del Alcantarillado , Contaminantes Químicos del Agua/químicaRESUMEN
Chromosome structure is dramatically altered upon entering meiosis to establish chromosomal architectures necessary for the successful progression of meiosis-specific events. An early meiotic event involves the replacement of the non-SMC mitotic cohesins with their meiotic equivalents in most part of the chromosome, forming an axis on meiotic chromosomes. We previously demonstrated that the meiotic cohesin complex is required for chromosome compaction during meiotic prophase in the fission yeast Schizosaccharomyces pombe. These studies revealed that chromosomes are elongated in the absence of the meiotic cohesin subunit Rec8 and shortened in the absence of the cohesin-associated protein Pds5. In this study, using super-resolution structured illumination microscopy, we found that Rec8 forms a linear axis on chromosomes, which is required for the organized axial structure of chromatin during meiotic prophase. In the absence of Pds5, the Rec8 axis is shortened whereas chromosomes are widened. In rec8 or pds5 mutants, the frequency of homologous chromosome pairing is reduced. Thus, Rec8 and Pds5 play an essential role in building a platform to support the chromosome architecture necessary for the spatial alignment of homologous chromosomes.
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Proteínas de Ciclo Celular/metabolismo , Emparejamiento Cromosómico , Cromosomas Fúngicos/genética , Meiosis , Fosfoproteínas/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismo , Schizosaccharomyces/genética , Proteínas de Ciclo Celular/genética , Fosfoproteínas/genética , Schizosaccharomyces/citología , Schizosaccharomyces/metabolismo , Proteínas de Schizosaccharomyces pombe/genéticaRESUMEN
The pairing and recombination of homologous chromosomes during the meiotic prophase is necessary for the accurate segregation of chromosomes in meiosis. However, the mechanism by which homologous chromosomes achieve this pairing has remained an open question. Meiotic cohesins have been shown to affect chromatin compaction; however, the impact of meiotic cohesins on homologous pairing and the fine structures of cohesion-based chromatin remain to be determined. A recent report using live-cell imaging and super-resolution microscopy demonstrated that the lack of meiotic cohesins alters the chromosome axis structures and impairs the pairing of homologous chromosomes. These results suggest that meiotic cohesin-based chromosome axis structures are crucial for the pairing of homologous chromosomes.
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Proteínas de Ciclo Celular/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Emparejamiento Cromosómico , Meiosis/fisiología , Cromosomas Fúngicos , Schizosaccharomyces/fisiología , CohesinasRESUMEN
Objective To observe decreased hearing in aged C57BL/6J mice, and to study pro- tective effects of Jian' erji ( JEJ ) for age-related hearing loss (AHL) and its possible mechanism. Methods Totally 36 C57BL/6J mice were randomly divided into four groups, i.e., the normal control group (n =6) , the AHL control group (n =12) , the high dose JEJ group (n =12) , the low dose JEJ group (n =6). Mice in the normal control group drank tap water from ablactation till 2 months old. Mice in the AHL control group drank tap water from ablactation till 7 months old. Mice in high and low dose JEJ groups drank JEJ at the daily dose of 3. 65 g/kg and 0. 91 g/kg respectively from ablactation till 7 months old. Six mice were selected from each group for auditory brainstem response (ABR) using brainstem evoked potentiometer on the day of ending the test. The cochlear tissue, auditory cortex, and liver were immediately collected from 6 mice of the high dose JEJ group and 6 of the AHL control group at the same ages. Contents of malondialdehyde (MDA) , end product of lipid peroxidation were detected by UV spectrophotometer using MDA coomassie blue kit. Results ABR thresholds evoked by short-pure tone from 4 to 48 KHz were in the normal range of 2 months old mice in the normal control group. Compared with 2 months old mice in the normal control group, ABR thresholds were significantly elevated in 7 months old mice of the AHL control group (P <0. 05). Significant differences also existed in ABR thresholds from 8 to 48 KHz in the high dose JEJ group (P <0. 05). Compared with 7 months old mice of the AHL control group, MDA contents in cochlear tissue, auditory cortex, and liver were obviously reduced in the high dose JEJ group (P <0. 01). Conclusions C57BL/6J mice showed significant symptoms of AHL in high frequency range at 7 months old. Daily drinking of high dose JEJ could significantly delay the occurrence and progress of AHL. Its protection might be related to antioxidant effects JEJ contained.
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Medicamentos Herbarios Chinos , Potenciales Evocados Auditivos del Tronco Encefálico , Presbiacusia , Animales , Cóclea , Medicamentos Herbarios Chinos/farmacología , Ratones , Ratones Endogámicos C57BL , Presbiacusia/prevención & controlRESUMEN
The development and utilization of lignocellulosic biomass resource becomes a major subject of widespread concern at home and abroad. To make better use of this resource and reduce cost, a thorough understanding of recalcitrance mechanism as well as chemical compositional and structural characteristics of lignocellulosic cell walls seems desiderated. With the property of fast testing, high sensitivity and simple sample preparation, FTIR microspectroscopy can provide microanalysis and nondestructive test. It has been proved to accurately present compositional and structural information of lignocellulosic cell walls and be suitable for the study of topochemistry of main components at the cellular level. After a brief introduction of the principle of FTIR microspectroscopy and its detailed experimental procedure, this review provides an overview on the feasibility of FTIR microspectroscopy in monitoring as well as evaluating the composition and structure of lignocellulosic cell walls from three aspects, including in situ distribution, changes after pretreatment and molecular orientation of the major components in cell walls. Some prospects, for example development of the magnification of the microscope and the spatial resolution of chemical imaging, combination with various analysis methods and instruments are also proposed. This technology can act as a new approach in characterizing lignocellulosic cell walls.
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Pared Celular/química , Lignina/química , Espectroscopía Infrarroja por Transformada de Fourier , Biomasa , MicroscopíaRESUMEN
Recent studies have identified a class of small non-coding RNA molecules, named microRNA (miRNA), that is dysregulated in malignant brain glioblastoma. Substantial data have indicated that miRNA-16 (miR-16) plays a significant role in tumors of various origins. This miRNA has been linked to various aspects of carcinogenesis, including cell apoptosis and migration. However, the molecular functions of miR-16 in gliomagenesis are largely unknown. We have shown that the expression of miR-16 in human brain glioma tissues was lower than in non-cancerous brain tissues, and that the expression of miR-16 decreased with increasing degrees of malignancy. Our data suggest that the expression of miR-16 and nuclear factor (NF)-κB1 was negatively correlated with glioma levels. MicroRNA-16 decreased glioma malignancy by downregulating NF-κB1 and MMP9, and led to suppressed invasiveness of human glioma cell lines SHG44, U87, and U373. Our results also indicated that upregulation of miR-16 promoted apoptosis by suppressing BCL2 expression. Finally, the upregulation of miR-16 in a nude mice model of human glioma resulted in significant suppression of glioma growth and invasiveness. Taken together, our experiments have validated the important role of miR-16 as a tumor suppressor gene in glioma growth and invasiveness, and revealed a novel mechanism of miR-16-mediated regulation in glioma growth and invasiveness through inhibition of BCL2 and the NF-κB1/MMP-9 signaling pathway. Therefore, our experiments suggest the possible future use of miR-16 as a therapeutic target in gliomas.
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Neoplasias Encefálicas/metabolismo , Proliferación Celular , Glioma/metabolismo , MicroARNs/fisiología , Proteínas Proto-Oncogénicas c-bcl-2/genética , Transducción de Señal , Animales , Apoptosis , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica , Glioma/genética , Glioma/patología , Humanos , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Desnudos , Persona de Mediana Edad , Subunidad p50 de NF-kappa B/metabolismo , Invasividad Neoplásica , Trasplante de Neoplasias , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Interferencia de ARN , Carga TumoralRESUMEN
Meiosis is a process of fundamental importance for sexually reproducing eukaryotes. During meiosis, homologous chromosomes pair with each other and undergo homologous recombination, ultimately producing haploid sets of recombined chromosomes that will be inherited by the offspring. Compared with the extensive progress that has been made in understanding the molecular mechanisms underlying recombination, how homologous sequences pair with each other is still poorly understood. The diversity of the underlying mechanisms of pairing present in different organisms further increases the complexity of this problem. Involvement of meiosis-specific noncoding RNA in the pairing of homologous chromosomes has been found in the fission yeast Schizosaccharomyces pombe. Although different organisms may have developed other or additional systems that are involved in chromosome pairing, the findings in S. pombe will provide new insights into understanding the roles of noncoding RNA in meiosis.
Asunto(s)
Emparejamiento Cromosómico/genética , Recombinación Homóloga/genética , Meiosis/genética , ARN no Traducido/genética , Cromosomas Fúngicos/genética , Haploidia , Schizosaccharomyces/genética , Telómero/genéticaRESUMEN
BACKGROUND: Gastric cancer is the third leading cause of cancer-related mortality in China, and the long-term survival for locally advanced gastric cancer is very poor. Simple surgery cannot yield an ideal result because of the high recurrence rate after tumor resection. Preoperative chemotherapy could help to reduce tumor volume, improve the R0 resection rate (no residual tumor after surgery), and decrease the risk of local tumor recurrence. The aim of this study was to evaluate the influence of pathological differentiation in the effect of preoperative chemotherapy for patients with locally advanced gastric cancer. METHODS: Patients with locally advanced gastric cancer (n = 32) received preoperative chemotherapy under the XELOX (capecitabine plus oxaliplatin) regimen. According to pathological examination, patients' tumors were classified into better (well and moderate) and poorly differentiated (lower differentiated and undifferentiated) groups, and the clinical response rate, type of gastrectomy, and negative tumor residual rate were compared between the two groups of patients. Morphological changes and toxic reactions were monitored after chemotherapy. RESULTS: The results showed that the clinical response rate in the better differentiated group was significantly higher than that in the poorly differentiated group (100% versus 25%, P = 0.000). The partial gastrectomy rate in the better differentiated group was significantly higher than that in the poorly differentiated group (87.5% versus 25% P = 0.000). A significant shrinking of tumor and necrosis of tumor tissues caused by chemotherapy could be observed. CONCLUSIONS: In conclusion, the better differentiated group with locally advanced gastric cancer is suitable for preoperative chemotherapy under the XELOX regimen, and as a result of effective preoperative chemotherapy, much more gastric tissue can be preserved for the better differentiated group.