Effect of acute phase cytokines on iron uptake in hepatocytes and differential localization of Lipocalin-2 and Transferrin receptors in rat hepatic and extra hepatic organs

Acute phase response (APR) is the systemic reaction to tissue injury and inflammation. It is clinically characterized by systemic symptoms such as fever, weakness, and anemia, somnolence loss of appetite and cytokines release. In the blood, it results in an increase in the plasma levels of a number of positive acute phase proteins (APPs), including clotting proteins, transport proteins, anti-proteases, and complement factors, with a concomitant decrease in negative APPs such as albumin. In addition, a decrease of serum iron-levels and consecutive increase of hepatic iron levels is also a hallmark of APR. This reaction is mediated by acute phase cytokines (APC) such as interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-6 cytokines through the activation of different transcription factors. The mechanism of liver iron uptake during APR is poorly understood. Therefore, current study aimed to investigate the exact mechanism of iron uptake with relation to iron regulatory proteins and their signaling pathway under the influence of APC in liver and liver cells. Furthermore, sub-cellular localization of these proteins in hepatic and extra-hepatic organs during APR is also examined. In vitro: primary cultures of rat isolated hepatocytes were stimulated with APC (IL-1β, IL-6 and TNF-α) in the presence/absence of different concentrations of iron (FeCl3: 0.01mM, 0.1mM). APR was induced by injecting turpentine-oil (TO) in hind limbs of rat and mice (wild type and IL-6 knock-out). Hepatocytes cell lysates and cell supernatants were prepared for iron measurement, RT-PCR and Western blotting. Tissue samples (liver, spleen and heart) were re-moved to use for immunobloting and immunohistochemical analysis.  In hepatocytes treated with iron in the presence/absence of cytokines, a significant iron up-take was detected with 0.1mM iron administration with a maximum (133µg/g protein) at 24h compared to control and other iron concentrations administrated. This iron uptake was further enhanced in the presence of acute phase cytokines with a maximum iron uptake (481µg/g of pro-tein) after concomitant administration of IL-6 and 0.1mM iron. Concomitantly, gene expression of LCN-2 and ferritin subunits (FTH, FTL) were up-regulated by iron and further induced by acute phase cytokines both, at mRNA and protein level. The maximum increase was seen for the combination of IL-6 with iron. TfR2 was increased by IL-6 and iron alone, however TfR1 was decreased. Combination of iron and APC abrogated the down-regulation of TfR1. Iron as well as APC stimulation led to LCN-2 release into supernatant, with increased release in the presence of iron and APC (IL-6 mainly) combined. Similar to in vitro data, liver tissue of rat and wild type mice also showed an increase in iron transport (TfR1, TfR2 and LCN-2) and storage proteins (FTH, FTL) during APR whereas such an increase was not detected for TfR2, LCN-2 and FTH in IL6-KO mice. In parallel to in-duction of iron transporters, a phosphorylation of STAT3 was also observed in WT-mice howev-er such a change was not noticed in IL-6 KO mice. Immunohistochemistry of hepatic and extra hepatic tissues indicated organ dependent local-ization of TfR1 and TfR2. TfR1 was primarily localized in the membrane and cytoplasm of liver, and spleen cells whereas, in both organs, TfR2 showed nuclear expression mostly. However, in heart, both TfR1 and TfR2 were detected to be surplus in membrane, cytoplasm and nucleus. In all the organs studied, TfR1, TfR2 and LCN-2 were colocalized. The iron storage protein FTL was detected in cytoplasm while a strong nuclear positivity for FTH was evident in the liver. Similarly, in spleen and heart FTL was detected mainly in the cytoplasm while FTH demonstrat-ed intense nuclear and a weak cytoplasmic expression. By summarizing, results of current study demonstrate that liver behaves as a “sponge” for iron during APR. Iron uptake in hepatocytes is tightly controlled by already present iron and this uptake can be further enhanced by APC, mainly by IL-6. Hepatocytes need more iron to respond the massive increase of protein synthesis under such stress conditions. These changes could ex-plain iron retention in hepatocytes during APR. Furthermore, portal blood iron is taken up by liver cells mostly through importer proteins (TfRs and LCN-2) and these proteins are regulated mainly through IL-6 activated STAT3 pathway. The differential localization pattern of iron regu-latory proteins in hepatic and extra-hepatic organs suggests their organ specific diverse role dur-ing APR.

Correlation between journal citation indices for Biochemistry and Molecular Biology Journals

This paper investigated the possibility of utilizing SCImago Journal Rank (SJR), Eigenfactor Score and Google H5 index indicator as an alternative to the Journal Impact Factor (JIF) for quality assessment in the field of biochemistry and molecular biology. Principal factors such as researchers and librarians concerns of methods of scientific journal ranking, publication of language, analysis time and self-citation impact are looked into across indicated options and alternatives. The SJR, ES, Google H5 and JIF scores and ranking order of biochemistry and molecular biology journals were downloaded from their relevant websites. Pearson’s and Spearman’s correlation coefficients were gauged to weigh relationship between these journal quality metrics. Nominated coefficients were embraced for evaluating direct and monotonic relationships of chosen variables and ranking measures. A constructive correlation was detected among the scores and ranking order based on SJR, ES, Google H5 and JIF of selected biochemistry and molecular biology journals. Consequently, scholars, academics and researchers in biochemistry and molecular biology can use the SJR, ES and Google H5 indicators as replacements to JIF for appraisal of scientific journals in the field

Indoor particulate matter in developing countries: a case study in Pakistan and potential intervention strategies

Around three billion people, largely in low and middle income countries, rely on biomass fuels for their household energy needs. The combustion of these fuels generates a range of hazardous indoor air pollutants and is an important cause of morbidity and mortality in developing countries. Worldwide, it is responsible for four million deaths. A reduction in indoor smoke can have a significant impact on lives and can help achieve many of the Millennium Developments Goals. This letter presents details of a seasonal variation in particulate matter (PM) concentrations in kitchens using biomass fuels as a result of relocating the cooking space. During the summer, kitchens were moved outdoors and as a result the 24 h average PM10, PM2.5 and PM1 fell by 35%, 22% and 24% respectively. However, background concentrations of PM10 within the village increased by 62%. In locations where natural gas was the dominant fuel, the PM concentrations within the kitchen as well as outdoors were considerably lower than those in locations using biomass. These results highlights the importance of ventilation and fuel type for PM levels and suggest that an improved design of cooking spaces would result in enhanced indoor air quality. © 2013 IOP Publishing Ltd

DOES BRAND EXTENSION IMPACT PARENT BRAND: A CASE OF JOHNSON, UK

Purpose of study: The main purpose of this study is to check the impact of brand extensions on brand image. For this purpose Johnson is selected as parent brand for current research. The targeted brand extensions are Johnson shampoo, Johnson’s isotonic drinks, Johnson’s sports wear and Johnson’s suntan lotion. Research Methodology: sample was selected from Bradford, UK. Sample consists of graduate students including males as well as female. Total sample size is 60 and data was collected through self administered questionnaires. For each brand 15 respondents were selected. Convenient sampling was selected as sampling technique. Results: Results show that Johnson’s have high brand awareness and perceived quality. While there is negative correlation results for brand fit on brand image for those product extensions which are not in same brand category i.e. Johnson’s sportswear and Johnson’s isotonic drinks. Conclusion: It is concluded from study results that launching new product in same parent brand category have high chance of success while in different category is risk.Brand Extension, Brand Fit, Johnson, Product extensions, marketing.

Measuring Push, Pull And Personal Factors Affecting Turnover Intention: A Case Of University Teachers In Pakistan

It has been observed that professional and qualified teacher’s retention become a challenge for Higher Education Institutions (HEIs) in Pakistan as the turnover rate has been significantly increased in recent years. The main objective of this paper is to access personal, push and pull factors and to find out that which factors contribute more to turnover intention. Primary data were collected from 100 teachers of 5 HEIs using questionnaire methods. The results indicate that all factors (personal, pull and push) have contributed in the employees’ turnover intentions. However, some facets of personal factor have significantly contributed in turnover intentions.Turnover, Higher Education Institution, Job Quit, Personal Factors, Push Factors, Pull Factors

E-BANKING: A CASE STUDY OF ASKARI COMMERCIAL BANK PAKISTAN

This paper has covered the operational issues related to e-banking as well as customer’s perception on usage of e-banking a case study of Askari Bank, Pakistan. 40 staff members and four customers are selected as sample for this study. Both qualitative and quantitative methods are used to present the results. Descriptive statistics is applied to describe the demographic variables while for operational problems correlation was used. Finally cross case analysis present customers’ perception about e-banking practices. Analysis shows that customer is not ready to adopt new technology that why their satisfaction level with e-banking is low. Internet speed and government policies are not supportive for e-banking in Pakistan. Due to lack of trust on technology and low computer literacy rate, customer hesitates to adopt new technology. : In order to promote IT culture in Pakistan, government has to reduce the internet rate. to promote the benefits of e-banking on media so that more user get facilitated from e-banking services.E-banking, Internet, ATM, Online transaction, E-readiness, Technology Acceptance Models

Local Government Systems and Decentralization: Evidence from Pakistan’s Devolution Plan

The discourse of governance and development practitioners continues to embrace community participation and community empowerment as an elementary means of building local capacity for poverty reduction, development and change at the local level. This article is a review of the decentralization initiatives of local government systems after the announcement of the devolution plan in Pakistan. It evaluates the initiatives’ participatory methods to ascertain the extent to which they have improved the process of community development at the local level. This article also measures the impact of community empowerment on the sustainability of community-driven projects implemented under the decentralization initiative through community-based organizations known as Citizen Community Boards (CCBs). Document analysis and literature review methodologies were employed to gain further insight into the decentralization phenomenon in Pakistan. The results describe human development, improvements in community empowerment and the sustainability of local projects; however, the sense of community has yet to be translated into shared benefits for rural communities. The fundamental goal of decentralization seems to be elusive because only power was transferred to the local level, whereas there is little support for community capacity building and community access to resources and the elites still control the electoral process. It is argued that community development initiatives in Pakistan require continuous support from local governments to boost local rural economies. Likewise, community-local government participatory development strategies can lead to strong local ownership and empowerment in rural communities

Decentralization and Participatory Rural Development: A Literature Review

Most of the developing nations are still struggling for efficient use of their resources. In order to overcome physical and administrative constraints of the development, it is necessary to transfer the power from the central government to local authorities. Distribution of power from improves the management of resources and community participation which is considered key to sustainable development. Advocates of decentralization argue that decentralized government is source to improve community participation in rural development. Decentralized government is considered more responsive towards local needs and development of poor peoples. There are many obstacles to expand the citizen participation in rural areas. There are many approaches for participatory development but all have to face the same challenges. Current paper highlights the literature about Decentralization and participatory rural development. Concept and modalities of Decentralization, dimensions of participation, types of rural participation and obstacles to participation are also the part of this paper