BRG1 interacts with SOX10 to establish the melanocyte lineage and to promote differentiation

Mutations in SOX10 cause neurocristopathies which display varying degrees of hypopigmentation. Using a sensitized mutagenesis screen, we identified Smarca4 as a modifier gene that exacerbates the phenotypic severity of Sox10 haplo-insufficient mice. Conditional deletion of Smarca4 in SOX10 expressing cells resulted in reduced numbers of cranial and ventral trunk melanoblasts. To define the requirement for the Smarca4 -encoded BRG1 subunit of the SWI/SNF chromatin remodeling complex, we employed in vitro models of melanocyte differentiation in which induction of melanocyte-specific gene expression is closely linked to chromatin alterations. We found that BRG1 was required for expression of Dct, Tyrp1 and Tyr, genes that are regulated by SOX10 and MITF and for chromatin remodeling at distal and proximal regulatory sites. SOX10 was found to physically interact with BRG1 in differentiating melanocytes and binding of SOX10 to the Tyrp1 distal enhancer temporally coincided with recruitment of BRG1. Our data show that SOX10 cooperates with MITF to facilitate BRG1 binding to distal enhancers of melanocyte-specific genes. Thus, BRG1 is a SOX10 co-activator, required to establish the melanocyte lineage and promote expression of genes important for melanocyte function

In search of negativity bias:An empirical study of perceived helpfulness of online reviews

A basic tenet of psychology is that the psychological effects of negative information outweigh those of positive information. Three empirical studies show that the negativity bias can be attenuated or even reversed in the context of electronic word-of-mouth (eWoM). The first study analyzes a large sample of customer reviews collected from Amazon.com and concludes that negative reviews are no more helpful than positive ones when controlling for review quality The second study follows up with a virtual experiment that confirms the lack of negativity bias in evaluating the helpfulness of online reviews. The third study demonstrates that the negativity effect can be reversed by manipulating the baseline valences. This work challenges the conventional wisdom of “bad is stronger than good” and contributes to the understanding of the eWoM phenomenon

Trans-anal full-thickness endoscopic resection of a rectal neuroendocrine neoplasia performed with TEO(\uae) (Karl-Storz microsurgery device) and laparoscopic ICG-guided lymphatic sampling - video vignette

Rectal neuroendocrine neoplasms (NEN) are increasingly diagnosed worldwide Compared to colonic NEN's, they are commonly smaller, less aggressive, with a low to intermediate grade of differentiation. A 5-year survival rate as high as 88% has been reported[1,2]. The risk of malignancy is closely related to tumour size, depth of invasion and lymph node involvement [1-3]. The incidence of lymph node metastasis increases with tumour (1-10mm 5.4%, 10-20mm 30%, >21mm 70%). The risk of lymph node metastasis increases with tumour depth (12% if submucosa is involved and 56% when the muscolaris propria is involved) [3-5]. This article is protected by copyright. All rights reserved

Ultrafast Processes in Isomeric Pyrene-N-methylacetamides: Formation of Hydrogen Bond Induced Static Excimers with Varied Coupling Strength

Pyrene based molecules are inclined to form excimers through self-association upon photoexcitation. In this work, the pyrene core is functionalized with N-methylacetamide group at the position 1 or 2, to develop pyren-1-methylacetamide (PyMA1) and pyren-2-methylacetamide (PyMA2), respectively. Upon photoexcitation, PyMA1 and PyMA2, at 1.0mM, in toluene, have formed predominantly static excimers. The steady state spectroscopic studies have showed that the excitonic coupling of PyMA1 dimers are much stronger in solution than its isomeric counterpart, PyMA2. The transient absorption (TA) measurements over fs-ps regime (fs-TA) showed that the formation of static excimers with the strongly-coupled pre-associated dimers, in PyMA1, happens in approx. 560fs, whereas, the excimers for the weakly-coupled pre-associated dimers in PyMA2 have formed in much slower time scale (approx. 65ps). The introduction of methylacetamide group at the position 1 or 2 on pyrene ring, was believed to have allowed forming hydrogen bonded excimers with different degrees of excitonic coupling

Mechanical performance and physico-chemical properties of limestone calcined clay cement (LC3) in Malawi

Malawi is one of the least-developed countries in Sub-Saharan Africa with disaster-prone housing infrastructure characterized by poor construction materials. Therefore, there is a need to provide resilient and cost-effective materials, such as limestone calcined clay cement (LC3). However, the exploitation of LC3 in Malawi is limited due to a lack of mineralogical information about the clays and limestone and related strength and durability when used as a cementitious material. In this study, the strength and physico-chemical properties of LC3 systems with 50% and 40% clinker contents (LC3-50 and LC3-40) were investigated. Cement mortar specimens were prepared at water to cement (w/c) ratios of 0.45, 0.5, and 0.6 with varying calcined clay (CC) to limestone (CC/LS) ratios (1:1, 2:1, and 3:1). The effects of CC/LS ratio on the fresh properties, strength, and durability were investigated. The results showed that specimens with 40% Portland cement replacement levels (LC3-40) exhibited higher standard consistency (up to 45%) than LC3-50, porosity in the range of 8.3–13.3%, and maximum water uptake in the range of 3.8–10.9%. On the other hand, LC3-50 samples offered the highest strength of approximately 40 MPa, complying with requirements for pozzolanic cementitious materials, whereas LC3-40 conforms to the strength requirements for masonry cements. This work shows that LC3 systems can be manufactured with local clays and limestone available in Malawi, and used as a sustainable construction material to mitigate carbon emissions as well as boost the local economy

Behind film performance in China’s changing institutional context:The impact of signals

Grounded in signaling theory, this paper investigates the signals reflecting product quality, innovativeness, reputation and cultural background which influence film performance, i.e. film survival (duration on cinema screen) and box office success, in China’s changing institutional context. This market has grown substantially and still possesses potential for further development. However, China’s unique institutional context presents challenges. By examining an expanded range of potential signals, two of which have not previously been examined in the literature, namely imported films and enhanced format film formats such as 3D and IMAX, we develop a conceptual framework and argue that signaling theory needs to be combined with institutional context. Similar to findings for film industries in other countries, we find quality and reputational signals including budget, star power, sequels, and online consumer reviews to be important in China. However, unique results are also revealed. Chinese consumers react to an innovativeness signal in that they are specifically attracted to enhanced format films. Film award nominations and prizes are insignificant reputational signals. Once other signals are taken into account, imported films on average do not perform as well as domestic films. We link these findings to China’s unique institutional setting and offer important implications for management, recognizing the challenges to film companies of competing in an increasingly globalized market. The paper is also of relevance to policymakers given their continued efforts in shaping the development of China’s film industry

Expression of NADPH Oxidase (NOX) 5 in Rabbit Corneal Stromal Cells

To determine whether NOX 5 is expressed in rabbit corneal stromal cells (RCSC). NADPH oxidases (NOXes) are enzymes that preferentially use NADPH as a substrate and generate superoxide. Several isoforms of NOXes function as multi-protein complexes while NOX5 and DUOXs do not require the accessory proteins for their activity and possess calcium binding EF hands.Human NOX5 primers were used to amplify the rabbit NOX5 by RT-PCR. Amplified product was sequenced to confirm its identity. The protein encoded by the NOX5 was identified by western blot analysis. NOX5 siRNA was used to reduce transcript, protein, and calcium stimulated activity. In silico analyses were performed to establish the putative structure, functions, and evolution of rabbit NOX5.NOX activity was measured in RCSC with NADPH rather than NADH as a substrate. RT-PCR with NOX5 primers amplified 288 bp product using RCSC cDNA, which, when sequenced, confirmed its identity to human NOX5 mRNA. This sequence was used to predict the rabbit (Oryctolagus cuniculus) NOX5 gene. NOX5 siRNA reduced amounts of NOX5 mRNA in RCSC and reduced ionomycin stimulated superoxide production. A protein of about 65 to 70 kDa encoded by the NOX5 was detected by western blot analysis. In silico analysis predicted a putative rabbit NOX5 protein containing 801 amino acids. Motif searches predicted the presence of at least 3 putative EF-hands in N-terminus and a NOX domain in C terminal region.The data document that the NOX5 gene was expressed in cells of lagomorphs unlike rodents, making the rabbit an interesting model to study NOX5 functions. The activity of the rabbit NOX5 was calcium stimulated, a trait of NOX5 in general. NOX5 may also prove to be a useful genetic marker for studying the taxonomic position of lagomorphs and the Glires classification

Peroxisome proliferator-activated receptor gamma and spermidine/spermine N(1)-acetyltransferase gene expressions are significantly correlated in human colorectal cancer

BACKGROUND: The peroxisome proliferator-activated receptor γ (PPARγ) is a transcription factor that regulates adipogenic differentiation and glucose homeostasis. Spermidine/spermine N(1)-acetyltransferase (SSAT) and ornithine decarboxylase (ODC) are key enzymes involved in the metabolism of polyamines, compounds that play an important role in cell proliferation. While the PPARγ role in tumour growth has not been clearly defined, the involvement of the altered polyamine metabolism in colorectal carcinogenesis has been established. In this direction, we have evaluated the PPARγ expression and its relationship with polyamine metabolism in tissue samples from 40 patients operated because of colorectal carcinoma. Since it is known that the functional role of K-ras mutation in colorectal tumorigenesis is associated with cell growth and differentiation, polyamine metabolism and the PPARγ expression were also investigated in terms of K-ras mutation. METHODS: PPARγ, ODC and SSAT mRNA levels were evaluated by reverse transcriptase and real-time PCR. Polyamines were quantified by high performance liquid chromatography (HPLC). ODC and SSAT activity were measured by a radiometric technique. RESULTS: PPARγ expression, as well as SSAT and ODC mRNA levels were significantly higher in cancer as compared to normal mucosa. Tumour samples also showed significantly higher polyamine levels and ODC and SSAT activities in comparison to normal samples. A significant and positive correlation between PPARγ and the SSAT gene expression was observed in both normal and neoplastic tissue (r = 0.73, p < 0.0001; r = 0.65, p < 0.0001, respectively). Moreover, gene expression, polyamine levels and enzymatic activities were increased in colorectal carcinoma samples expressing K-ras mutation as compared to non mutated K-ras samples. CONCLUSION: In conclusion, our data demonstrated a close relationship between PPARγ and SSAT in human colorectal cancer and this could represent an attempt to decrease polyamine levels and to reduce cell growth and tumour development. Therefore, pharmacological activation of PPARγ and/or induction of SSAT may represent a therapeutic or preventive strategy for treating colorectal cancer

The role of retailer's performance in optimal wholesale price discount policies

The main goal of this paper is to model the effects of wholesale price control on manufacturer’s profit, taking explicitly into account the retailer’s sales motivation and performance. We consider a stylized distribution channel where a manufacturer sells a single kind of good to a single retailer. Wholesale price discounts are assumed to increase the retailer’s motivation thus improving sales. We study the manufacturer’s profit maximization problem as an optimal control model where the manufacturer’s control is the discount on wholesale price and retailer’s motivation is one of the state variables. In particular in the paper we prove that an increasing discount policy is optimal for the manufacturer when the retailer is not efficient while efficient retailers may require to decrease the trade discounts at the end of the selling period. Computational experiments point out how the discount on wholesale price passed by the retailer to the market (passthrough) influences the optimal profit of the manufacturer