259 research outputs found
bioaerosol emission characteristics and the epidemiological, occupational, and public health risk assessment of waste and wastewater management
No full textFunding Information: H&TRC author gratefully acknowledge the FCT/MCTES national support through the UIDB/05608/2020 and the UIDP/05608/2020.publishersversionpublishe
CIC de novo loss of function variants contribute to cerebral folate deficiency by downregulating FOLR1 expression
No full textBackground Cerebral folate deficiency (CFD) syndrome is characterised by a low concentration of 5-methyltetrahydrofolate in cerebrospinal fluid, while folate levels in plasma and red blood cells are in the low normal range. Mutations in several folate pathway genes, including FOLR1 (folate receptor alpha , FRα) , DHFR (dihydrofolate reductase) and PCFT (proton coupled folate transporter ) have been previously identified in patients with CFD. Methods In an effort to identify causal mutations for CFD, we performed whole exome sequencing analysis on eight CFD trios and identified eight de novo mutations in seven trios. Results Notably, we found a de novo stop gain mutation in the capicua (CIC) gene. Using 48 sporadic CFD samples as a validation cohort, we identified three additional rare variants in CIC that are putatively deleterious mutations. Functional analysis indicates that CIC binds to an octameric sequence in the promoter regions of folate transport genes: FOLR1 , PCFT and reduced folate carrier (Slc19A1; RFC1 ). The CIC nonsense variant (p.R353X) downregulated FOLR1 expression in HeLa cells as well as in the induced pluripotent stem cell (iPSCs) derived from the original CFD proband. Folate binding assay demonstrated that the p.R353X variant decreased cellular binding of folic acid in cells. Conclusion This study indicates that CIC loss of function variants can contribute to the genetic aetiology of CFD through regulating FOLR1 expression. Our study described the first mutations in a non-folate pathway gene that can contribute to the aetiology of CFD.Background Cerebral folate deficiency (CFD) syndrome is characterised by a low concentration of 5-methyltetrahydrofolate in cerebrospinal fluid, while folate levels in plasma and red blood cells are in the low normal range. Mutations in several folate pathway genes, including FOLR1 (folate receptor alpha , FRα) , DHFR (dihydrofolate reductase) and PCFT (proton coupled folate transporter ) have been previously identified in patients with CFD. Methods In an effort to identify causal mutations for CFD, we performed whole exome sequencing analysis on eight CFD trios and identified eight de novo mutations in seven trios. Results Notably, we found a de novo stop gain mutation in the capicua (CIC) gene. Using 48 sporadic CFD samples as a validation cohort, we identified three additional rare variants in CIC that are putatively deleterious mutations. Functional analysis indicates that CIC binds to an octameric sequence in the promoter regions of folate transport genes: FOLR1 , PCFT and reduced folate carrier (Slc19A1; RFC1 ). The CIC nonsense variant (p.R353X) downregulated FOLR1 expression in HeLa cells as well as in the induced pluripotent stem cell (iPSCs) derived from the original CFD proband. Folate binding assay demonstrated that the p.R353X variant decreased cellular binding of folic acid in cells. Conclusion This study indicates that CIC loss of function variants can contribute to the genetic aetiology of CFD through regulating FOLR1 expression. Our study described the first mutations in a non-folate pathway gene that can contribute to the aetiology of CFD
Studies of p53-dependent growth arrest and apoptosis in friend erythroleukemia cells
No full textThe p53 tumour suppressor promotes cell-cycle arrest or apoptosis in response to cellular stress such as DNA damage and oncogenesis. It is not clear why p53 induces only G1 arrest in some cells but apoptosis in others. This thesis aims at understanding the mechanisms that govern cell-fate determination after p53 activation.
Murine erythroleukemia cells that lack endogenous p53 expression were transfected with a temperature-sensitive (ts) p53 allele. The erythroleukemia cells responded to p53 activation by undergoing G1 arrest, apoptosis and differentiation. Addition of a cytokine such as erythropoietin, c-kit ligand or interleukin-3 to the culture medium blocked p53-mediated apoptosis and differentiation but not p53-mediated G1 arrest. These observations indicate that apoptosis and G1 arrest can be effectively uncoupled through the action of cytokines acting as survival factors and are consistent with the idea that apoptosis and G1 arrest represent separate functions of p53. These experiments also demonstrate that the cellular environment plays an important role in the cell-fate determination after p53 activation. Further analysis of the EPO signalling pathways indicated that the EPO-mediated cell survival depends on JAK2 but independent of STAT5 and PI3′K.
The function of p53 as a tumour suppressor depends, at least in part, on its ability to bind to specific DNA sequences and activate transcription of target genes. p21WAF1 is the primary effector in p53-dependent G1 arrest. The pathways through which p53 promotes apoptosis, however, are not fully understood. We identified a number of p53 responsive genes by using differential display to analyze global gene expression in the murine erythroleukemia cells before and after the is p53 was activated. One of the new genes, which we named PIDD, encodes a predicted protein with a death domain. Pidd mRNA was induced by ionizing radiation in a p53-dependent manner and the basal level of Pidd RNA was dependent on p53 status. Overexpression of Pidd inhibited cell growth in a p53-like manner by inducing apoptosis. Antisense inhibition of Pidd expression attenuated p53-mediated apoptosis. Our data suggest that Pidd is an effector of p53-dependent apoptosis.Ph.D
Dummy molecularly imprinted mesoporous silicates for selective adsorption of 2-naphthol
No full textDummy molecularly imprinted mesoporous silicates (MIMS-2) were made by co-condensation of tetraethyl orthosilicate (TEOS) with precursors of bi-functional mimic of 2-naphthol, 2,7-dihydroxynaphthalene, around triblock copolymer surfactant Pluronic (P123) micelles. The bi-functional template was linked to two functional monomers through thermally cleavable covalent bonds to generate imprint precursor. This provides the possibility of incorporating the target into the cross-linked mesoporous silicate matrix in the non-ionic surfactant templated sol-gel process. P123 was eluted by ethanol extraction and template molecules were removed by refluxing the materials in a mixture of dimethyl sulfoxide (DMSO) and water. MIMS-1 was prepared similarly except that 2-naphthol was used as template instead of 2,7-dihydroxynaphthalene. Solid phase extraction studies showed that MIMS-2 exhibited good retention and selectivity for 2-naphthol among its structural analogues. The mono-functional molecule 2-naphthol was unable to be incorporated into the silica matrix of mesoporous material by the identical method, and the resulting material MIMS-1 exhibits poor selectivity to the template analogues
A mammary repopulating cell population characterized in mammary anlagen reveals essential mammary stroma for morphogenesis
No full textThe cells with mammary repopulating capability can achieve mammary gland morphogenesis in a suitable cellular microenvironment. Using cell surface markers of CD24, CD29 and CD49f, mouse mammary repopulating unit (MRU) has been identified in adult mammary epithelium and late embryonic mammary bud epithelium. However, embryonic MRU remains to be fully characterized at earlier mammary anlagen stage. Here we isolated discrete populations of E14.5 mouse mammary anlagen cells. Only Lin(-)CD24(med)CD29(+) cell population was predicted as E14.5 MRU by examining their capacities of forming mammosphere and repopulating cleared mammary fat pad in vivo. However, when we characterized gene expressions of this E14.5 cell population by comparing with adult mouse MRU (Lin(-)CD24(+)CD29(hi)), the gene profiling of these two cell populations exhibited great differences. Real-time PCR and immunostaining assays uncovered that E14.5 Lin(-)CD24(med)CD29(+) cell population was a heterogeneous stroma-enriched cell population. Then, limiting dilutions and single-cell assays also confirmed that E14.5 Lin(-)CD24(med)CD29(+) cell population possessed low proportion of stem cells. In summary, heterogeneous Lin(-)CD24(med)CD29(+) cell population exhibited mammary repopulating ability in E14.5 mammary anlagen, implying that only suitable mammary stroma could enable mammary gland morphogenesis, which relied on the interaction between rare stem cells and microenvironment. (C) 2014 Elsevier Inc. All rights reserved.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000341341700012&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701OncologyCell BiologySCI(E)[email protected]
Sinicization and Taiwanization in early postwar Taiwan (1945-1949) : the creation of an indigenous historical narrative within official cultural policy
No full textTaiwan’s early postwar cultural field saw a struggle between Chinese waisheng officials and Taiwanese bensheng intellectuals over the direction of Taiwan’s cultural rebuilding project, and how it should treat the legacy of fifty years of Japanese colonial rule. This thesis shows that during the period from its founding until the February 28 Incident in 1947, the magazine Taiwan Culture, in its unique inclusion of both Taiwanese and Chinese voices, secured a site of constructive, critical engagement on the question of what should constitute a Taiwanese identity through engagement with Taiwan’s history, the diversity of its colonial and anti-colonial experience, and its unique linguistic and literary traditions. By situating its two most influential bensheng editors Yang Yunping and Su Xin within the contemporary field, this thesis contrasts their individual political positions, analyzes their dispositions toward the KMT’s cultural renovation project, and contextualizes their written work to understand how they adapted their rhetoric and public appeals to Taiwan Culture as a semi-official site of debate. This thesis finds that, though participation in Taiwan Culture by Yang and Su required the moderation of certain political speech, it was seen as a crucial means by which to retain official support and acknowledgment of efforts to further realize a historically self-determined Taiwanese identity.published_or_final_versionChineseMasterMaster of Philosoph
Sea surface temperature oscillations in southern Okinawa Trough during last 2700 years from ODP Hole 195-1202B
No full textMost of the temperature reconstructions for the past two millennia are based on proxy data from various sites on land. Here we present a bidecadal resolution record of sea surface temperature (SST) in Southern Okinawa Trough for the past ca. 2700 years by analyzing tetraether lipids of planktonic archaea in the ODP Hole 1202B, a site under the strong influence of Kuroshio Current and East Asian monsoon. The reconstructed SST anomalies generally coincided with previously reported late Holocene climate events, including the Roman Warm Period, Sui-Tang dynasty Warm Period, Medieval Warm Period, Current Warm Period, Dark Age Cold Period and Little Ice Age. However, the Medieval Warm Period usually thought to be a historical analogue for the Current Warm Period has a mean SST of 0.6-0.8°C lower than that of the Roman Warm Period and Sui-Tang dynasty Warm Period. Despite an increase since 1850 AD, the mean SST in the 20th century is still within the range of natural variability during the past 2700 years. A close correlation of SST in Southern Okinawa Trough with air temperature in East China, intensity of East Asian monsoon and the El-Niño Southern Oscillation index has been attributed to the fluctuations in solar output and oceanic-atmospheric circulation
Microbial population structure in near-ground aerosols during fog-haze days in northern China
No full textStudies on microbial populations in near-ground aerosols during fog-haze days could help enhance our knowledge concerning the relationship between fog-haze and human health. In this study, microbial populations in aerosols near-ground during a fog-haze event in Beijing were analyzed using clone library methods. Results showed that the bacterial diversity in aerosols during fog-haze days was lower than that after fog-haze days. Proteobacteria alone and Proteobacteria with Firmicutes were respectively detected in 1.5 and 20 m aerosols during fog-haze days. In addition to Proteobacteria and Firmicutes, Bacteroidetes alone and Acidobacteria with Verrucomicrobia were respectively found in aerosols at 20 and 1.5 m after fog-haze days. The fungal species observed during fog-haze days were completely different from those detected after fog-haze days. Ascomycota and Basidiomycota were respectively detected during and after fog-haze days. The distribution of microbial diversity in aerosols exhibited meteorological and site-associated variations. The same potential pathogenic microorganisms were detected at different heights during fog-haze days. This study on the characteristics of microbial population in aerosols could provide a comprehensive understanding of the factors causing the harmful effects of particles on humans during fog-haze days
A possible positive feedback of reduction of precipitation and increase in aerosols over eastern central China
No full text- …
