Nicotine, IFN-γ and retinoic acid mediated induction of MUC4 in pancreatic cancer requires E2F1 and STAT-1 transcription factors and utilize different signaling cascades

BACKGROUND: The membrane-bound mucins are thought to play an important biological role in cell–cell and cell–matrix interactions, in cell signaling and in modulating biological properties of cancer cell. MUC4, a transmembrane mucin is overexpressed in pancreatic tumors, while remaining undetectable in the normal pancreas, thus indicating a potential role in pancreatic cancer pathogenesis. The molecular mechanisms involved in the regulation of MUC4 gene are not yet fully understood. Smoking is strongly correlated with pancreatic cancer and in the present study; we elucidate the molecular mechanisms by which nicotine as well as agents like retinoic acid (RA) and interferon-γ (IFN-γ) induce the expression of MUC4 in pancreatic cancer cell lines CD18, CAPAN2, AsPC1 and BxPC3. RESULTS: Chromatin immunoprecipitation assays and real-time PCR showed that transcription factors E2F1 and STAT1 can positively regulate MUC4 expression at the transcriptional level. IFN-γ and RA could collaborate with nicotine in elevating the expression of MUC4, utilizing E2F1 and STAT1 transcription factors. Depletion of STAT1 or E2F1 abrogated the induction of MUC4; nicotine-mediated induction of MUC4 appeared to require α7-nicotinic acetylcholine receptor subunit. Further, Src and ERK family kinases also mediated the induction of MUC4, since inhibiting these signaling molecules prevented the induction of MUC4. MUC4 was also found to be necessary for the nicotine-mediated invasion of pancreatic cancer cells, suggesting that induction of MUC4 by nicotine and other agents might contribute to the genesis and progression of pancreatic cancer. CONCLUSIONS: Our studies show that agents that can promote the growth and invasion of pancreatic cancer cells induce the MUC4 gene through multiple pathways and this induction requires the transcriptional activity of E2F1 and STAT1. Further, the Src as well as ERK signaling pathways appear to be involved in the induction of this gene. It appears that targeting these signaling pathways might inhibit the expression of MUC4 and prevent the proliferation and invasion of pancreatic cancer cells

Marine climate and fisheries scenario of Maharashtra Climcard-4

Marine climate and fisheries scenario of Maharashtra Climcard-

Points of Interest Coverage with Connectivity Constraints using Wireless Mobile Sensors

Part 7: Network Topology ConfigurationInternational audienceThe coverage of Points of Interest (PoI) is a classical requirement in mobile wireless sensor applications. Optimizing the sensors self-deployment over a PoI while maintaining the connectivity between the sensors and the sink is thus a fundamental issue. This article addresses the problem of autonomous deployment o f mobile sensors that need to cover a predefined PoI with a connectivity constraints and provides the solution to it using Relative Neighborhood Graphs (RNG). Our deployment scheme minimizes the number of sensors used for connectivity thus increasing the number of monitoring sensors. Analytical results, simulation results and real implementation are provided to show the efficiency of our algorithm

SARS CoV-2 aggravates cellular metabolism mediated complications in COVID-19 infection.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the primary causative organism in corona virus disease-19 (COVID-19) infections, is a novel member of the human coronavirus family which was first identified in Wuhan, China, towards the end of 2019. This letter reveals new vital missing links in our current understanding of the mechanisms that lead to cell death triggered by ferroptotic stress in COVID-19 infection. It further reveal the importance of homocysteine mediated trans-sulfuration pathway in COVID-19 infection. Hence, Vitamin B6, folic acid, and Vitamin B12 should be incorporated in the treatment regimen for SARS CoV-2 infections to suppress complications, as the virus mediates altered host cell metabolism

Overcoming drug delivery barriers and challenges in topical therapy of atopic dermatitis: A nanotechnological perspective.

Atopic dermatitis (AD) is an inflammatory disorder centered around loss of epidermal barrier function, and T helper 2 (Th2) immune responses. The current understanding of disease heterogeneity and complexity, limits the rational use of existing topical, systemic therapeutic agents, but paves way for development of advanced therapeutic agents. Additionally, advanced nanocarriers that deliver therapeutics to target cells, seem to offer a promising strategy, to overcome intrinsic limitations and challenges of conventional, and traditional drug delivery systems. Ever-evolving understanding of molecular target sites and complex pathophysiology, adverse effects of current therapeutic options, inefficient disease recapitulation by existing animal models are some of the challenges that we face. Also, despite limited success in market translatibility, nanocarriers have demonstrated excellent preclinical results and have been extensively studied for AD. Detailed research on behavior of nanocarriers in different patients and tailored therapy to account for phenotypic variability of the disease are the new research avenues that we look forward to

Sea erosion threat to coastal fishing villages of Valsad district, Gujarat

A report on severe sea erosion in some of the coastal fishing villages like Moti Danti, Nani Danti and Udwada, situated at the mouth of river Ambika, Valsad District of Gujarat, during the monsoon period of 1986. Many of the huts were destroyed, fish drying yards were washed away and standing paddy crops were damaged adversely affecting the life in the village

Unprecedented landings of Indian Mackerel in Maharashtra

Unprecedented landings of Indian Mackerel, Rastrelliger kanagurta was observed in Maharashtra during October to December 2010. Estimated catch of mackerel was 21,761 t that contributed 18.2% to the total marine fish landings of the state, replacing the resource on the second position after prawns in the order of abundance

Shrimp fishery by mini-trawling along Alleppey coast, Kerala

Penaeid shrimps from nearshore waters in 5-12 m depth range are regularly exploited by plank built boats locally known as murivallan which operate mini - trawl (cod end mesh size 15-20 mm) along Alleppey coast in Kerala. Observations made for three seasons at Valanjavazhy (1994-97) and at Pallithode (2002-05) indicated that 935 t (cpue 42 kg) and 145 t (37kg) of shrimps were landed by mini-trawl at these centres respectively. The fishing season extended from September to MayIJune depending on the onset of monsoon. Parapenaeopsis stylifera and Metapenarus dobsoni were the main contributors to the shrimp fishery. While the former predominated (91%) the fishery at Valanjavazhi, both the species showed almost equal representation at Pallithode. Species-wise details on size distribution, sex ratio, maturity and spawning season have been indicated. In spite of discarding smaller P. stylifera (< 41 mm in total length), the commercial catch at Valanjavazhy consisted more than 50% juveniles during many months in the observation period. I stylifera completes its nursery phase in the nearshore areas along the coast and fishing them at this stage is detrimental to the fishery of this species. The impact of mini-trawl operation on the shrimp resources off Kerala along with possible management measures is discussed