Regulation and function of MYBBP1A in cellular senescence and pathogenesis of head and neck cancer

Myb-binding protein 1A (MYBBP1A) is a nucleolar protein implicated in stress response and carcinogenesis. However, its functional contribution to cellular senescence as well as the clinical relevance in head and neck squamous cell carcinoma (HNSCC) have not been addressed so far. In the present study, a cell culture model of genotoxic senescence, which was induced by the topoisomerase II inhibitor VP-16, was established to unravel the role of MYBBP1A in cellular senescence. Interestingly, in response to DNA damage, MYBBP1A first translocate from the nucleolus to the nucleoplasm and subsequently, its protein levels decreased in senescent cells. Loss-of-function approaches in tumor cell lines provided further evidence that silencing of MYBBP1A was not sufficient to trigger senescence, but that it modulated the efficacy of genotoxic-induced senescence and augments resistance to irradiation. Although, the precise molecular mechanism by which MYBBP1A regulates DNA damage-induced senescence remains elusive and warrants further investigation, this study revealed an inverse regulation of MYBBP1A and AKT(Ser473) phosphorylation to be a characteristic feature of senescent tumor cells. Most strikingly, immunohistochemical analysis of tissue microarrays with tumor specimens from primary oropharyngeal squamous cell carcinoma (OPSCC) patients (n=61) revealed that a MYBBP1AlowpAKT(Ser473)high staining pattern serves as an independent marker for poor clinical outcome. Remarkably a significant correlation with progression-free or overall survival was not found considering pAKT(Thr308) levels, suggesting a more critical role of the mTOR/AKT pathway for the clinical behavior of OPSCCs with low MYBBP1A levels. In summary, these data demonstrate that tumor cells with a MYBBP1Alow but pAkt(Ser473)high protein pattern have a senescent-like phenotype and might critically contribute to tumor progression due to the emergence of highly malignant and/or therapy resistant tumor cells. Moreover, the abundance of MYBBP1AlowpAKT(Ser473)high senescent tumor cells in primary tumors as well as following tumor relapse could serve as a reliable biomarker for treatment decision making and to stratify HNSCC patients at high-risk for treatment failure. Thus, restoration of MYBBP1A function or pharmacological inhibition of the PI3K/mTOR/AKT pathway is an attractive new concept not only to sensitize tumor cells for available treatment options, but also to establish new strategies for targeted therapy with the potential of elimination of senescent cells

Prototyping Things:Reflecting on Unreported Objects of Design Research for IoT

Prototypes and other ‘things’ have had many uses in HCI research—to help understand a problem, as a stepping stone towards a solution, or as a final outcome of a research process. However, within the messy context of a research through design project, many of these roles do not form part of the final research narratives, restricting the ability of other researchers to learn from this practice. In this paper we revisit prototypes used in three different design research projects, conducted over a period when the Internet of Things emerged into everyday life, exploring complex hidden relationships between the internet, people and physical objects. We aim to explore the unreported roles that prototypes played in these projects, including brokering relationships with participants and deconstructing opaque technologies. We reflect on how these roles align with existing understandings of prototypes in HCI, with particular attention to how these roles can contribute to design around IoT

Opposing function of MYBBP1A in proliferation and migration of head and neck squamous cell carcinoma cells

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent and lethal cancers worldwide and mortality mostly results from loco-regional recurrence and metastasis. Despite its significance, our knowledge on molecular, cellular and environmental mechanisms that drive disease pathogenesis remains largely elusive, and there are limited therapeutic options, with only negligible clinical benefit. METHODS: We applied global gene expression profiling with samples derived from a recently established mouse model for oral cancer recurrence and identified a list of genes with differential expression between primary and recurrent tumors. RESULTS: One differentially expressed gene codes for Myb-binding protein 1a (MYBBP1A), which is known as a transcriptional co-regulator that physically interacts with nuclear transcription factors, such as NFκB and p53. We confirmed significantly reduced MYBBP1A protein levels on tissue sections of recurrent mouse tumors compared to primary tumors by immunohistochemistry, and found aberrant MYBBP1A protein levels also in tumor samples of HNSCC patients. Interestingly, silencing of MYBBP1A expression in murine SCC7 and in human HNSCC cell lines elicited increased migration but decreased cell growth. CONCLUSION: We provide experimental evidence that MYBBP1A is an important molecular switch in the regulation of tumor cell proliferation versus migration in HNSCC and it will be a major challenge for the future to proof the concept whether regulation MYBBP1A expression and/or function could serve as a novel option for anti-cancer therapy

Inhibitory Potential of Chromene Derivatives on Structural and Non-Structural Proteins of Dengue Virus

Dengue fever is a mosquito-borne viral disease that has become a serious health issue across the globe. It is caused by a virus of the Flaviviridae family, and it comprises five different serotypes (DENV-1 to DENV-5). As there is no specific medicine or effective vaccine for controlling dengue fever, there is an urgent need to develop potential inhibitors against it. Traditionally, various natural products have been used to manage dengue fever and its co-morbid conditions. A detailed analysis of these plants revealed the presence of various chromene derivatives as the major phytochemicals. Inspired by these observations, authors have critically analyzed the anti-dengue virus potential of various 4H chromene derivatives. Further, in silico, in vitro, and in vivo reports of these scaffolds against the dengue virus are detailed in the present manuscript. These analogues exerted their activity by interfering with various stages of viral entry, assembly, and replications. Moreover, these analogues mainly target envelope protein, NS2B-NS3 protease, and NS5 RNA-dependent RNA polymerase, etc. Overall, chromene-containing analogues exerted a potent activity against the dengue virus and the present review will be helpful for the further exploration of these scaffolds for the development of novel antiviral drug candidates

WATER QUALITY ANALYSIS: A CASE STUDY IN BYRAMANGALA LAKE WATER AND SURROUNDING GROUND WATER

A study was carried out to find out the water quality of Byramangala lake of Ramanagara district. The water quality of Byramangala lake water and ground water from bore wells situated in the area within 600 meters surrounding the lake was analyzed. The quality analysis of various parameters such as BODs, COD, DO, E-Coli, and pH, Total Dissolved Solids, Total Suspended Solids and Total Hardness were tested. In addition, the presence of metals such as Cadmium (Cd), Chromium (Cr), Lead (Pb), and Iron (Fe) in the lake water and ground water samples were tested. Results for the various tests conducted showed similar trends for both lake water and ground water. It was observed that certain parameters such as BOD5, and COD were beyond permissible limits as per the BIS standards for drinking water. A few remedial measures have been proposed that may help in mitigating the pollution in the selected project area Byramangala Lake

Not Available

Not AvailableNot AvailableNot Availabl