1,720,965 research outputs found
Calcium bursts allow rapid reorganization of EFhD2/Swip-1 cross-linked actin networks in epithelial wound closure
No full textChanges in cell morphology require the dynamic remodeling of the actin cytoskeleton. Calcium fluxes have been suggested as an important signal to rapidly relay information to the actin cytoskeleton, but the underlying mechanisms remain poorly understood. Here, we identify the EF-hand domain containing protein EFhD2/Swip-1 as a conserved lamellipodial protein strongly upregulated in Drosophila macrophages at the onset of metamorphosis when macrophage behavior shifts from quiescent to migratory state. Loss- and gain-of-function analysis confirm a critical function of EFhD2/Swip-1 in lamellipodial cell migration in fly and mouse melanoma cells. Contrary to previous assumptions, TIRF-analyses unambiguously demonstrate that EFhD2/Swip-1 proteins efficiently cross-link actin filaments in a calcium-dependent manner. Using a single-cell wounding model, we show that EFhD2/Swip-1 promotes wound closure in a calcium-dependent manner. Mechanistically, our data suggest that transient calcium bursts reduce EFhD2/Swip-1 cross-linking activity and thereby promote rapid reorganization of existing actin networks to drive epithelial wound closure
Silencing of ZRF1 impedes survival of estrogen receptor positive MCF-7 cells and potentiates the effect of curcumin
No full textThe role and clinical implication of ZRF1 in breast cancer are poorly understood. So this study is aimed to explore the role of ZRF1 in breast cancer progression. With this context, we first assessed its expression pattern in FFPE primary and metastasis breast tissue samples as well as from publicly available databases. Moreover, we also explored the survival status of patients from the publicly available database and interestingly discover that high expression of ZRF1 decreases the survival of estrogen-positive breast cancer patients more than estrogen-negative status patients. In the perspective of this, we evaluated the role ZRF1 in MCF-7 breast cancer cells and found that it's silencing by knockdown results in decreased cell proliferation as well as cell viability. Results also show that expression of ZRF1 is down regulated in the presence of estrogen-depleted conditions but independent of RAS/MEK as well as AKT axes. Moreover, the decrease in viability of MCF-7 cells was accompanied by induction of apoptosis and DNA damage, well-marked with upregulation of cleaved PARP and downregulation of BCL2 and H2AUbK119 levels. Furthermore, we also explored that knockdown of ZRF1 sensitises the effect of curcumin, observed with decrease in cell viability and dropping of IC50 value from 25 to 15 mu M. This investigation thus shed a new light on the role on ZRF1 in breast cancer cells and hence can be exploited to design better therapeutic intervention.NIT-Rourkela; DST, Government of Indi
A novel single-cell RNA-sequencing approach and its applicability connecting genotype to phenotype in ageing disease
No full textSingle cell multi-omics analysis has the potential to yield a comprehensive understanding of the cellular events that underlie the basis of human diseases. The cardinal feature to access this information is the technology used for single-cell isolation, barcoding, and sequencing. Most currently used single-cell RNA-sequencing platforms have limitations in several areas including cell selection, documentation and library chemistry. In this study, we describe a novel high-throughput, full-length, single-cell RNA-sequencing approach that combines the CellenONE isolation and sorting system with the ICELL8 processing instrument. This method offers substantial improvements in single cell selection, documentation and capturing rate. Moreover, it allows the use of flexible chemistry for library preparations and the analysis of living or fixed cells, whole cells independent of sizing and morphology, as well as of nuclei. We applied this method to dermal fibroblasts derived from six patients with different segmental progeria syndromes and defined phenotype associated pathway signatures with variant associated expression modifiers. These results validate the applicability of our method to highlight genotype-expression relationships for molecular phenotyping of individual cells derived from human patients.Georg-August-Universität GöttingenOpen-Access-Publikationsfonds 202
Investigation of Epigenetic Regulation of Tumor Suppressor Genes by Inhibition of Histone Deacetylases and Lipid Raft Signaling in Human Cancers
No full textTumor development and cancer progression are principally guided by predominant role of oncogenes over tumor suppressor genes. Rejuvenation of tumor suppressor genes (TSGs) could be one of the therapeutic strategies against cancer. This thesis attempts to illuminate the regulatory mechanism behind TSG silencing by targeting histone deacetylases (HDACs) and lipid raft signaling. In view of dynamic and reversible nature of histone acetylation and overexpression of HDAC enzymes in cancer, HDACs were targeted by inhibitors that owe the ability to restore the expression of TSGs. The present thesis elucidates a novel property of Thymoquinone (TQ), an active principle of Nigella sativa, as an efficient inhibitor against histone deacetylases (HDACs). It reveals the molecular interaction of TQ with HDACs, especially HDAC1 and HDAC2. TQ could efficiently reactivate the expression of p21, maspin, insulin like growth factor binding protein7 (IGFBP7) and microtubule-associated tumor suppressor gene (MTUS1).
The epigenetic regulation of IGFBP7 in breast cancer has neither been studied adequately nor has its connection with lipid raft been investigated previously. This study reveals that downregulation of IGFBP7 is mostly due to histone modifications rather than DNA methylation in breast cancer. Perturbation of signaling pathways is one of the quintessential factors responsible for aberrant expression of TSGs in cancer. Therefore, modulation of IGFBP7 by lipid raft signaling is examined in breast cancer. It is apparent that lipid raft/RAS-MAPK signaling is involved in epigenetic regulation of IGFBP7 gene.
The role and regulation of MTUS1 in lung cancer is still in its infancy. The study delineates that the regulation of MTUS1 is independent of lipid raft inhibition. However, epigenetic mechanism plays a crucial role in its regulation. Human Males absent on the first (hMOF) and DNA methyltransferase 1 (DNMT1) are frequently over expressed in lung cancer. It is apparent from the results in the thesis that both DNMT1 and hMOF may be correlated with MTUS1 silencing in lung cancer. Further experiments through inhibition of DNMT1 and hMOF demonstrated the expression of MTUS1, which in turn attenuate proliferation and migration of lung cancer cells. Taken together this thesis emphasized TQ as an inhibitor of HDACs that helps expression of TSGs, like p21, Maspin and Bax and describes the importance of lipid raft signaling and epigenetic modulation of IGFBP7 and MTUS1
A novel single-cell RNA-sequencing platform and its applicability connecting genotype to phenotype in ageing-disease
No full text
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
- …
