IRF4 Essay

“Assess own leadership behaviours and potential in the context of a particular leadership model and own organisation’s working practices and culture using feedback from others”

iRobot is a very competitive firm in the robotics industry that creates many types of robots from consumer cleaning robots to drones used for military applications. In the last few years, the sales of the consumer products have been driving the majority of iRobot’s revenues. The company has a few, albeit experienced, competitors in the consumer market while in the military robotics market the company has battled with industry veterans such as Lockheed Martin. The financial structure of the company had been strong until the worldwide economic crisis hit in 2008.

It is of great interest to see how far the scientific community has come across with identifying the genes and functions of each encoding protein. The science brought different interventions, as each gene has the possibility of interaction and the whole cellular environment has a type of role to engage in the complex day to day regulation of our eukaryotic cells.

An example of this is a DNA construct with a primer located at -909 bp to -421 bp from the TSS. This specific region acts as an inhibitor, and we know this to be true because once it was removed, luciferase activity increased. These locations on the genomic DNA suggest possible sequences that, like mentioned before, are likely to be involved in regulating ITGB6 transcription. This leads to the next experiment used, which is called promoter deletion analysis. The authors assay the sequence deletions of the promoter in order to determine which one of those sequences within the 1,117 bp are the main elements that affect ITGB6 transcription. The results of deleting certain fragments of sequences showed that the region from -421 bp to -150 bp upstream of the TSS had the highest activity in the ITGB6 gene expression. When that region got deleted, gene expression levels dropped. Further deletion from -150 bp to -3 bp completely wiped it out. This decrease provides us some insight on the mechanism of ITGB6 transcription regulation, which ultimately answers the authors’ research

59 NF-κB presents in an inactive state, this molecule could be either homo- or heterodimers subunit in the cytoplasm, with dimers bound by the inhibitory κB protein (IκB). In the activation pathway, NF-κB activated by many steps that are begins by the activation of IκB kinase (IKK). IKK activation then results in phosphorylation

TLR4-dependent activation of NF-kB and CREB co-regulate the NRF1 promoter with NF-kB intronic enhancement leading to NRF-1 synthesis and nuclear translocation, followed by target gene expression(Suliman et al., 2010b). This also requires mitochondrial H2O2 production and identifies NRF-1 as an early-phase component of the host defense regulated by TLR signaling and by redox

MALAT1 co-localizes to nuclear speckles with SRSF1 and has been shown to regulate AS by modulating cellular levels of SRSF1 phosphorylation. SRSF1 binding sites have also been found at the 5’ end of both human and mouse MALAT1. Interestingly, we have shown that the RNA-recognition motif 2 (RRM2) of SRSF1 interacts with the RS domain and that this interaction facilitates the proper directional phosphorylation mechanism seen for proper SRSF1 nuclear translocation. Scientific literature and empirical evidence regarding the relationships between SRSF1, p53/OIS, and MALAT1 have led us to our central hypothesis that MALAT1 overexpression disrupts the interaction between the RRM2 and RS domain in SRSF1, subsequently impairing its phosphorylation and thus its nuclear translocation. This change in subcellular localization, in turn, destabilizes p53, leading to loss of OIS in cervical cancer cells. We will address this hypothesis in the following Specific Aims:

Specific Aim 1: Determine if overexpression of RNP-4F in Drosophila embryos alters target gene expression

Silva et al. (Ref. 83) have performed a comprehensive analysis of the inactivation mechanisms (mutation, homozygous and hemizygous deletion, and promoter hypermethylation) in of 100 primary breast carcinomas. RT-PCR showed expression variable of the p14ARF transcript, with 17% overexpression and 26% decreased expression. No detectable alterations were observed in the majority of cases with overexpressed p14ARF mRNA, but 77% of tumors with decreased expression showed one or more of these genetic alterations (Ref. 83). A significant correlation was observed between decreased p14ARF expression and poor prognostic parameters. The same group later studied the inactivation mechanisms that alter the levels (Ref. 84). Furthermore, the interdependence of inactivation mechanisms was studied since it had been reported that p14ARF was altered in tumors in concordance with p16INK4a. They showed that promoter hypermethylation was the major mechanism of inactivation of these genes, which was present in 31% and 50% of the tumors that showed decreased p16INK4a and p14ARF expression, respectively. No detectable inactivation mechanisms were observed in tumors overexpressing p16INK4a or p14ARF. In conclusion, these tumor suppressor proteins were often co-altered in human breast

If the monoclonal antibodies are not successful at stopping their corresponding interferon type’s activity then we should see all the Vk∗MYC mice that received concentrated interferon solution express more antitumor activity and more severe symptoms. Additionally, if any interferon type has an adverse reaction with another type of interferon, we should see that reflected in the Vk∗MYC mice as well. For example, if type 3 interferon replaces type 1 interferon due to their similar activity, but type 3 interferon is also limited in its expression only to epithelial cells, then Vk∗MYC mice who receive monoclonal antibodies preventing type 3 interferon signaling should express more antitumor activity, as multiple myeloma is not expressed in mucosal tissues.

It is important to describe an analysis of the relationship for exploration of intra-species variation and it has been seen that variation in DNA regulatory elements are common and a fraction of it directly falls at TFBSs. 12 Drosophila species have been analyzed in order to see the sequence variation at each motif position and the results showed that motifs are conserved and depressed level of variation has been shown across individuals. It is observed that, an introduction of transcription factor binding variability, which has been taken into account transforms itself in a sort of motif match related to mutation and enables the researchers to investigate and make it possible to analyze TFBS related hurdles and operational constraints which shares medical or related biological attributes.

This research paper is about “An analysis of variation at transcription factor binding sites in Drosophila and humans”. This analysis is done in order to investigate the transcription factor binding sites variability with the comparison of ready published data of transcription factor binding maps for Drosophila isogenic lines and human individuals.

IRF-1 has antiviral, immunomodulatory, apoptotic, and immune cell differentiation effects. Experiments in IRF-1 knockout mice have demonstrated that IRF-1 is a key regulator of macrophage function, NK cell response, Th1/Th2 differentiation, and DC differentiation (94-97). IRF-1 is involved in the regulation of many genes during inflammation, immune responses, and cell proliferation. IRF-1 interacts with both IRF-2 and IRF-8 as an antagonist. IRF-2 is an antagonist that represses IRF-1 function by competing for IRF-1 binding sites, and IRF-8 inhibits IRF-1 function by directly binding to it (98, 99). IRF-7 is considered the “master” regulator of type I IFN signalling due to its role in providing the second stronger wave of type 1 IFNs. Honda et al. showed that in mice deficient in the IRF-7 gene that IRF-7 is required for the initiation of IFN-α/β genes by the MyD88-dependent pathway and the MyD88-independent pathway (10). It has been reported that IRF-7 is expressed at low levels in most cell types (78). The low levels of IRF-7 expression suggest that IRF-3 is mainly responsible for the initial induction of IFN, where IRF-7 is responsible for the later up regulation (78). This suggests a positive feedback loop where IRF-7 induced IFN expression is involved in the second and larger IFN induction step, which allows for efficient upregulation of type I IFNs during viral infection (78, 100, 101). IRF-7 expression is tightly regulated to prevent excessive tissue

Using a combination of IHC and IF experiments, we confirmed that the protein level of E2F3A and E2F8 during cell cycle, which reached peak at G1-early S and late S-G2, respectively, while E2F4 translocates from cytoplasm to nuclear when cells exit cell cycle. The activator E2Fs are required for transcriptional activation of S phase genes, while pocket protein needs to be phosphorylated by cyclin/CDK complexes to release its inhibitory effect on the activator E2Fs [10, 12, 29, 30]. The atypical repressor E2Fs function as transcriptional repressors of genes involved in DNA replication, inactivation of atypical repressor E2F activity would extend the progression of the DNA synthesis machinery [4, 5, 9, 16]. The typical repressor

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