CD180/RP105 Toll-like Receptor (TLR) mediated signalling in Chronic Lymphocytic Leukaemia

The role of the microenvironment in the development and progression of chronic lymphocytic leukaemia (CLL) is currently of major interest. Pathogen- and damage-associated molecular patterns (PAMPs and DAMPs, respectively) represent exogenous and endogenous microenvironmental factors acting via a range of receptors, including Toll-like receptors (TLR). CD180/RP105 is a membrane-associated orphan receptor that belongs to the TLR family, is expressed by professional antigen-presenting cells, and drives normal B-cell activation and proliferation. We have previously shown that approximately 60% of CLL samples expressed surface CD180 but only half responded to ligation with anti-CD180 monoclonal antibody (mAb) resulting in activation, cycling, and reduced basal apoptosis and were termed responders (R). In contrast, CD180+CLL samples that failed to respond to anti-CD180 mAb, despite expressing a high density of CD180 receptors, were termed non-responders (NR). We further demonstrated that in R-CLL cells, CD180 ligation significantly induced phosphorylation of ZAP70/Syk, ERK, p38MAPK, and AKT. In contrast, CD180-mediated signalling in NR CLL cells did not progress downstream from ZAP70/Syk phosphorylation indicating a block in activation of downstream protein kinases, and possible anergy. To further clarify the CD180-mediated signalling pathways in CLL, here we studied signal transduction downstream from ZAP70/Syk by delineating CLL samples into R and NR through their proximal ability to activate AKT. We have studied major signalling protein kinases associated with the BCR signalling pathway: PI3K, Btk, ERK, p38MAPK and AKT. Segregation of CLL samples responding to CD180 ligation by signalling via pAKT, rather than by CD86 upregulation, revealed that CD180 ligation on CLL cells can activate two alternative signalling pathways: pro-survival that operates via PI3K-Btk-AKT protein kinases, or mostly pro-apoptotic, that operates via p38MAPK but not through Btk. This may have implications for CLL therapy where Btk inhibitors are being used. Here we demonstrate that albeit ligation of sIgM alone also activates pro-survival PI3K-Btk-AKT pathway pre-engagement of CD180 redirected BCR-mediated signalling towards the potentially pro-apoptotic p38MAPK pathway that opens new horizons for immunotherapy. Since the tissue microenvironment plays a crucial role in generation and survival of the CLL clones, studies pertaining to CD180 expression in the lymphoid tissues were undertaken. Our pilot data suggests that in normal tonsils CD180 is expressed by the mantle zone (MZ) B cells and not the germinal centre (GC) B cells. However in CLL lymph nodes complete obliteration of the normal tissue architecture and a weak expression of CD180 has been detected, whilst expression of CD180 on bone marrow CLL cells was heterogeneous. Since CLL cells migrate to and from the solid tissues into the peripheral circulation in any CLL clone, there is always an intra-clonal kinetic heterogeneity through a suggested continuum between the 'proliferative' or CXCR4dimCD5bright, and 'resting' CXCR4 brightCD5dim fractions. Here we report that the 'resting' compartment was enriched for CD180+ cells compared to the 'proliferating' subset. In contrast, sIgM+ cells were more frequent in the proliferating fraction. Since the “resting” subset of CLL cells is also considered as the one “returning” to the solid tissues supported by the increased expression of CXCR4, our data might suggest possible attraction of the CD180+ cells towards the putative ligand in the lymphoid tissues. It is becoming apparent that intraclonal diversity plays an important role in the clinical outcome of patients with CLL. Subsets of the CLL clone that respond more robustly to external stimuli may well gain a growth and survival advantage and possibly promote clonal evolution. Identification of these CLL subpopulations was therefore of prime importance, as these cells may be preferred targets for future therapeutics. We have established that CD180 expression on CLL cells helps identifying different subsets and delineating their physiological status. Our findings on modulation of signalling pathways through CD180 and sIgM and the temporal effects of their ligation is consistent with multiple ligands in the, in vivo, microenvironment playing an important role in the survival of CLL cells. Since TLR can shuttle between inhibition and promotion of leukemic growth they may play a key role in immune evasion impacting on clinically relevant tumour-host microenvironment interactions. The identification of distinct CD180-mediated signalling pathways that promote tumour cell proliferation and survival will allow specific targeting of key players in the pathways with immunotherapy and chemotherapy

Decarbonisation of olefin processes using biomass pyrolysis oil

An imperative step toward decarbonisation of current industrial processes is to substitute their petroleum-derived feedstocks with biomass and biomass-derived feedstocks. For decarbonisation of the petrochemical industry, integrated catalytic processing of biomass pyrolysis oil (also known as bio-oil) is an enabling technology. This is because, under certain conditions, the reaction products form a mixture consisting of olefins and aromatics, which are very similar to the products of naphtha hydro-cracking in the conventional olefin processes. These synergies suggest that the catalytic bio-oil upgrading reactors can be seamlessly integrated to the subsequent separation network with minimal retrofitting costs. In addition, the integrated catalytic processing provides a high degree of flexibility for optimization of different products in response to market fluctuations. With the aim of assessing the techno-economic viability of this pathway, five scenarios in which different fractions of bio-oil (water soluble/water insoluble) were processed with different degrees of hydrogenation were studied in the present research. The results showed that such a retrofit is not only economically viable, but also provides a high degree of flexibility to the process, and contributes to decarbonisation of olefin infrastructures. Up to 44% reductions in greenhouse gas emissions were observed in several scenarios. In addition, it was shown that hydrogen prices lower than 6 $/kg will result in bio-based chemicals which are cheaper than equivalent petrochemicals. Alternatively, for higher hydrogen prices, it is possible to reform the water insoluble phase of bio-oil and produce bio-based chemicals, cheaper than petrochemical equivalents

Comparative Cytotoxicity of Glycyrrhiza glabra Roots from Different Geographical Origins Against Immortal Human Keratinocyte (HaCaT), Lung Adenocarcinoma (A549) and Liver Carcinoma (HepG2) Cells

Glycyrrhiza glabra L. (Fabaceae), commonly known as 'liquorice', is a well-known medicinal plant. Roots of this plant have long been used as a sweetening and flavouring agent in food and pharmaceutical products, and also as a traditional remedy for cough, upper and lower respiratory ailments, kidney stones, hepatitis C, skin disorder, cardiovascular diseases, diabetes, gastrointestinal ulcers and stomach ache. Previous pharmacological and clinical studies have revealed its antitussive, antiinflammatory, antiviral, antimicrobial, antioxidant, immunomodulatory, hepatoprotective and cardioprotective properties. While glycyrrhizin, a sweet-tasting triterpene saponin, is the principal bioactive compound, several bioactive flavonoids and isoflavonoids are also present in the roots of this plant. In the present study, the cytotoxicity of the methanol extracts of nine samples of the roots of G.-glabra, collected from various geographical origins, was assessed against immortal human keratinocyte (HaCaT), lung adenocarcinoma (A549) and liver carcinoma (HepG2) cell lines using the in vitro 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazoliumbromide cell toxicity/viability assay. Considerable variations in levels of cytotoxicity were observed among various samples of G.-glabra

Perceptions of International Students in Indian Higher Education Campuses

The global competition for international students has fuelled the need for education providers to become more consumer oriented in their planning. Our purpose with this study was to understand international student perceptions and discuss corresponding approaches. In this qualitative study we interviewed twenty international students enrolled in two Indian universities to examine: one, their feelings about being an international student in India and two, what attracted them to India as a higher education destination. Our findings suggest that, the people on campus and in the host city are vital to delivering experiences. We identified “quality of education,” “cultural diversity” and the “rapidly growing economy” as the most noteworthy among several factors that have motivated the selection of India as a host country. We discuss the findings through different conceptual lenses and implications for managers have been presented. This research acts as market intelligence input to the Indian HE policy makers and university leaders

PACK: Prediction-Based Traffic Redundancy Elimination System & provide secure encryption in Cloud

In this paper, we use concept of PACK (predictive ACKs), which act like a traffic redundancy elimination (TRE) system, designed for cloud computing customers. TRE is designed on cloud to reduce traffic as well as cost regarding TRE Computation and storage will be optimized. The main advantage of the Pack Cloud-server is its ability to span end clients TRE effort, thus minimizing processing costs prompted by the TRE Algorithm. Unlike previous solutions Pack does not require server to continuously keep track on customer to maintain the status of the server.Pack maintain computing environment that combine server and client movement to maintain cloud elasticity. Pack is based on TRE technology; TRE is used to eliminate the transmission of redundant content as well as allow client to use newly received chunk to identify previously received chunks chains, which in turn can be used as reliable predictors future transmitted chunks.In our proposed work we are using encryption concept. we will send the chunks in encrypted format. For encryption we are using AES algorithm which is based on symmetric block cipher. This is using for security Purpose. We are going to secure our file from other traffics

Optimized Bus Management System through Analysing the Density of Bus Commuters and Delay

Transport demand in most Indian cities has increased significantly due to increase in population. Public transport especially buses are getting crowded day-by-day due to heavy demand of transport facility. This has led to unregulated planning of the frequency of buses to be allocated different areas. Either the buses lines up at one time or buses get delayed for a long time. In some areas there are very few buses allocated at a very crowded route .Also there are buses lined up on the route where hardly commuters travel. This limitation of management has incurred loss in the bus management system. Hence we have proposed and implemented a system in which the number of passengers in a bus stop can be calculated and the bus service can be regulated depending on the passengers arrival. Also due to our system there has been efficient distribution of the buses on the required routes and this benefits the bus management system by reducing the loss they are facing nowadays. It also calculates the time delay a bus may take considering different parameters that may affect it to be late . It also verifies the cost generated against the actual cost collected as well benefits the commuters indirectly. All this would be done using a web application available to employees at different positions

Utilization of the ability to induce activation of the nuclear factor (erythroid-derived 2)-like factor 2 (Nrf2) to assess potential cancer chemopreventive activity of liquorice samples

Introduction – Nuclear factor (erythroid-derived 2)-like factor 2 (Nrf2) is a transcription factor that regulates expression of many detoxification enzymes. Nrf2-antioxidant responsive element (Nrf2-ARE) signalling pathway can be a target for cancer chemoprevention. Glycyrrhiza glabra, common name, ‘liquorice’, is used as a sweetening and flavouring agent, and traditionally, to treat various ailments, and implicated to chemoprevention. However, its chemopreventive property has not yet been scientifically substantiated. Objective – To assess the ability of liquorice root samples to induce Nrf2 activation correlating to their potential chemopreventive property. Methods – The ability of nine methanolic extracts of liquorice root samples, collected from various geographical origins, to induce Nrf2 activation was determined by the luciferase reporter assay using the ARE-reporter cell line, AREc32. The antioxidant properties were determined by the 2,2-diphenyl-1-picryhydrazyl (DPPH) and the ferric-reducing antioxidant power (FRAP) assays. Results – All extracts exhibited free-radical-scavenging property (RC50 = 136.39-635.66 g/mL). The reducing capacity of ferrous ion was 214.46-465.59 M Fe(II)/g. Nrf2 activation indicated that all extracts induced expression of ARE-driven luciferase activity with a maximum induction of 2.3 fold relative to control. These activities varied for samples from one geographical location to another. Conclusions – The present findings add to the existing knowledge of cancer chemoprevention by plant-derived extracts or purified phytochemicals, particularly the potential use of liquorice for this purpose

An overview of E-learning Tools and Analysis of its Awareness among Management Students

Management students are supposed to have not only the strong theoretical foundation but also the knowledge of current affairs, strong analytical skills, decision making skills etc. E-learning tools offer many of advantage to improve the quality of education through interactive teaching learning environment. This study is one of the steps towards analyzing the awareness & use of internet as well as e-learning tools by management students in NMU region and an overview of E-Learning Tools. It is based on primary data that is collected through structured questionnaire. Analysis reveals that students are available with sufficient time to spend on internet. Similarly internet tools are used to collect information & theory contents only and its use for interactive processes is very limited. Based on aforesaid analysis, it is concluded that adoption of digital teaching learning environment in North Maharashtra University is very limited. And students themselves are not well trained to use e-learning tools to the full extent. Hence there is need of digital approach in management education

Feasibility of Virtual Lifestyle Physical Activity Program for South Asian Indian Immigrant Women: Dance and Spousal/Partner Dyad Meetings

Culturally relevant, physical activity (PA) interventions are important in lowering the risk of cardiovascular disease (CVD) in South Asian Indian immigrant (SAI) women. This 12-week study aimed to determine the feasibility (recruitment, engagement, satisfaction, obtaining measures, retention) of implementing a virtual lifestyle PA program. The outcomes measured included steps/day; minutes of moderate-vigorous PA (MVPA/week) and cardiovascular health measures (aerobic fitness, blood pressure, body mass index, and waist circumference) in women. The intervention targets included benefits/barriers to PA, self-efficacy, social support, and couples’ satisfaction. We recruited six SAI spousal/partner dyads (women aged 40-65 years; \u3c 7,500 average steps/day). The intervention included: (a) Fitbit for PA prescription and step goal setting for women; (b) Bollywood-style women-only weekly dance sessions via Zoom; and (c) dyad behavioral group meetings every two weeks via Zoom. Dance and group meeting attendance for women was 100%. The majority (83.3%) wore a Fitbit \u3e 91.6% of days. Overall mean client satisfaction was five on a five-point satisfaction scale. Aerobic fitness and self-efficacy for PA improved significantly (t = 3.50, p = \u3c .05) at 12 weeks with no significant changes in steps/MVPA/physical measures. This virtual lifestyle PA program to stimulate and maintain lifestyle PA is culturally acceptable to SAI women. Keywords: South Asian Indian women, physical activity, virtual dance, spousal/partner dyad, feasibilit