33 research outputs found
Exploring the big data paradox for various estimands using vaccination data from the global COVID-19 Trends and Impact Survey (CTIS)
Selection bias poses a challenge to statistical inference validity in
non-probability surveys. This study compared estimates of the first-dose
COVID-19 vaccination rates among Indian adults in 2021 from a large
non-probability survey, COVID-19 Trends and Impact Survey (CTIS), and a small
probability survey, the Center for Voting Options and Trends in Election
Research (CVoter), against benchmark data from the COVID Vaccine Intelligence
Network (CoWIN). Notably, CTIS exhibits a larger estimation error (0.39)
compared to CVoter (0.16). Additionally, we investigated the estimation
accuracy of the CTIS when using a relative scale and found a significant
increase in the effective sample size by altering the estimand from the overall
vaccination rate. These results suggest that the big data paradox can manifest
in countries beyond the US and it may not apply to every estimand of interest
Lyl1 interacts with CREB1 and alters expression of CREB1 target genes
AbstractThe basic helix-loop-helix (bHLH) transcription factor family contains key regulators of cellular proliferation and differentiation as well as the suspected oncoproteins Tal1 and Lyl1. Tal1 and Lyl1 are aberrantly over-expressed in leukemia as a result of chromosomal translocations, or other genetic or epigenetic events. Protein-protein and protein-DNA interactions described so far are mediated by their highly homologous bHLH domains, while little is known about the function of other protein domains. Hetero-dimers of Tal1 and Lyl1 with E2A or HEB, decrease the rate of E2A or HEB homo-dimer formation and are poor activators of transcription. In vitro, these hetero-dimers also recognize different binding sites from homo-dimer complexes, which may also lead to inappropriate activation or repression of promoters in vivo. Both mechanisms are thought to contribute to the oncogenic potential of Tal1 and Lyl1. Despite their bHLH structural similarity, accumulating evidence suggests that Tal1 and Lyl1 target different genes. This raises the possibility that domains flanking the bHLH region, which are distinct in the two proteins, may participate in target recognition. Here we report that CREB1, a widely-expressed transcription factor and a suspected oncogene in acute myelogenous leukemia (AML) was identified as a binding partner for Lyl1 but not for Tal1. The interaction between Lyl1 and CREB1 involves the N terminal domain of Lyl1 and the Q2 and KID domains of CREB1. The histone acetyl-transferases p300 and CBP are recruited to these complexes in the absence of CREB1 Ser 133 phosphorylation. In the Id1 promoter, Lyl1 complexes direct transcriptional activation. We also found that in addition to Id1, over-expressed Lyl1 can activate other CREB1 target promoters such as Id3, cyclin D3, Brca1, Btg2 and Egr1. Moreover, approximately 50% of all gene promoters identified by ChIP-chip experiments were jointly occupied by CREB1 and Lyl1, further strengthening the association of Lyl1 with Cre binding sites. Given the newly recognized importance of CREB1 in AML, the ability of Lyl1 to modulate promoter responses to CREB1 suggests that it plays a role in the malignant phenotype by occupying different promoters than Tal1
The zinc finger domain of Wilms' tumor 1 suppressor gene (WT1) behaves as a dominant negative, leading to abrogation of WT1 oncogenic potential in breast cancer cells
Abstract
Introduction
There is growing evidence that the Wilms' tumor 1 suppressor gene (WT1) behaves as an oncogene in some forms of breast cancer. Previous studies have demonstrated that the N-terminal domain of WT1 can act as a dominant negative through self-association. In the studies presented here we have explored the potential for the zinc finger domain (ZF) of WT1 to also have dominant-negative effects, and thus further our understanding of this protein.
Methods
Using full-length and ZF-only forms of WT1 we assessed their effect on the WT1 and c-myc promoter using luciferase and chromatin immunoprecipitation assays. The gene expression levels were determined by quantitative real-time RT-PCR, northern blot and western blot. We also assessed the effect of the ZF-only form on the growth of breast cancer cell lines in culture.
Results
Transfection with WT1–ZF plasmids resulted in a stronger inhibition of WT1 promoter than full-length WT1 in breast cancer cells. The WT1–ZF form lacking the lysine–threonine–serine (KTS) insert (ZF - KTS) can bind to the majority of WT1 consensus sites throughout the WT1 promoter region, while the ZF containing the insert (ZF + KTS) form only binds to sites in the proximal promoter. The abundances of endogenous WT1 mRNA and protein were markedly decreased following the stable expression of ZF - KTS in breast cancer cells. The expressions of WT1 target genes, including c-myc, Bcl-2, amphiregulin and TERT, were similarly suppressed by ZF - KTS. Moreover, WT1–ZF - KTS abrogated the transcriptional activation of c-myc mediated by all four predominant isoforms of WT1 (including or lacking alternatively spliced exons 5 and 9). Finally, WT1–ZF - KTS inhibited colony formation and cell division, but induced apoptosis in MCF-7 cells.
Conclusion
Our observations strongly argue that the WT1–ZF plasmid behaves as a dominant-negative regulator of the endogenous WT1 in breast cancer cells. The inhibition on proliferation of breast cancer cells by WT1–ZF - KTS provides a potential candidate of gene therapy for breast cancer
Comparative Study on the Effect of Ethephon Treatment on the Growth of Two Grape Varieties Kyoho and Shine-Muscat
[Objectives] This study aimed to study the effect of ethephon treatment on the growth of two main grape varieties Kyoho and Shine-Muscat. [Methods] Two-year-old Kyoho and Shine-Muscat grape plants transplanted in the film-covered steel-framed greenhouse were used as the test materials. They were pruned horizontally and linearly. In the late growth period, the new shoots were sprayed with ethephon (1 500Ă—). During the germination period, 10 plants were randomly selected for each variety to investigate the germination situation. Before flowering, 20 new shoots with uniform growth were randomly selected for each variety to investigate the growth. During the fruit maturity period, 10 clusters of fruits were randomly selected for each variety to determine the related indices of fruit quality. [Results] After the treatment with ethephon, the germination, new shoot growth and fruit quality differed between the two varieties. Overall, the thickness of main stem, main vine and new shoot of Shine-Muscat was greater than that of Kyoho, and the length of new shoot of Kyoho was significantly greater than that of Shine-Muscat. [Conclusions] The growth of Shine-Muscat was more robust. There was little difference in the ear weight of natural fruit setting between the two varieties. Shine-Muscat showed high sugar and low acid contents than Kyoho
3D printing critical materials for rechargeable batteries: from materials, design and optimization strategies to applications
Three-dimensional (3D) printing, an additive manufacturing technique, is widely employed for the fabrication of various electrochemical energy storage devices (EESDs), such as batteries and supercapacitors, ranging from nanoscale to macroscale. This technique offers excellent manufacturing flexibility, geometric designability, cost-effectiveness, and eco-friendliness. Recent studies have focused on the utilization of 3D-printed critical materials for EESDs, which have demonstrated remarkable electrochemical performances, including high energy densities and rate capabilities, attributed to improved ion/electron transport abilities and fast kinetics. However, there is a lack of comprehensive reviews summarizing and discussing the recent advancements in the structural design and application of 3D-printed critical materials for EESDs, particularly rechargeable batteries. In this review, we primarily concentrate on the current progress in 3D printing (3DP) critical materials for emerging batteries. We commence by outlining the key characteristics of major 3DP methods employed for fabricating EESDs, encompassing design principles, materials selection, and optimization strategies. Subsequently, we summarize the recent advancements in 3D-printed critical materials (anode, cathode, electrolyte, separator, and current collector) for secondary batteries, including conventional Li-ion (LIBs), Na-ion (SIBs), K-ion (KIBs) batteries, as well as Li/Na/K/Zn metal batteries, Zn-air batteries, and Ni–Fe batteries. Within these sections, we discuss the 3DP precursor, designprinciples of 3D structures, and working mechanisms of the electrodes. Finally, we address the major challenges and potential applications in the development of 3D-printed critical materials for rechargeable batteries
Alteration of expression of WT1 target genes in zinc finger domain lacking KTS-transfected MCF-7 cells
<p><b>Copyright information:</b></p><p>Taken from "The zinc finger domain of Wilms' tumor 1 suppressor gene (WT1) behaves as a dominant negative, leading to abrogation of WT1 oncogenic potential in breast cancer cells"</p><p>http://breast-cancer-research.com/content/9/4/R43</p><p>Breast cancer research : BCR 2007;9(4):R43-R43.</p><p>Published online 16 Jul 2007</p><p>PMCID:PMC2206716.</p><p></p> Transient and stable transfectants of MCF-7 cells were analyzed for the expression of Wilms' tumor 1 suppressor gene (WT1) target genes or nontarget genes (horizontal axis) with quantitative real-time PCR assays. The relative expression (vertical axis) of these genes in the transfected MCF-7 cells was calculated as compared with the pcDNAcontrol. Results are the average of three experiments. AREG, amphregulin; BASP1, brain acid soluble protein 1; KTS, lysine–threonine–serine; WT1, Wilms' tumor 1 suppressor gene; ZF, zinc finger domain
Inhibition of transcriptional activity of the WT1 promoter by its zinc finger domain
<p><b>Copyright information:</b></p><p>Taken from "The zinc finger domain of Wilms' tumor 1 suppressor gene (WT1) behaves as a dominant negative, leading to abrogation of WT1 oncogenic potential in breast cancer cells"</p><p>http://breast-cancer-research.com/content/9/4/R43</p><p>Breast cancer research : BCR 2007;9(4):R43-R43.</p><p>Published online 16 Jul 2007</p><p>PMCID:PMC2206716.</p><p></p> Schematic drawing for luciferase reporter constructs. The predominant transcription start site (+1) is indicated by an arrow. Small solid triangles indicate Wilms' tumor 1 suppressor gene (WT1) binding sites. MCF-7 cells and MDA468 cells were co-transfected with plasmids expressing the WT1 proteins (either pcDNAcontrol (CON), aminoterminal-only construct N-WT1, zinc finger domain lacking or with lysine–threonine–serine (ZF - KTS or ZF + KTS) or full-length WT1 vectors A~D), and either the pGL2 vector control or the differential WT1 promoter-driven luciferase constructs (horizontal axis), respectively. Luciferase activity was normalized with β-galactosidase activity and is expressed in relative luciferase activity as compared with the luciferase vector control (vertical axis). Results are the average of three experiments