Enterotoxigenic Escherichia coli (ETEC) cause hundreds of millions of cases of infectious diarrhea annually, predominantly in children from low-middle income regions. Notably, in children, as well as volunteers challenged with ETEC, diarrheal severity is significantly increased in blood group A (bgA) individuals. EtpA, is a secreted glycoprotein adhesin that functions as a blood group A lectin to promote critical interactions between ETEC and blood group A glycans on intestinal epithelia for effective bacterial adhesion and toxin delivery. EtpA is highly immunogenic resulting in robust antibody responses following natural infection and experimental challenge of volunteers with ETEC. To understand how EtpA directs ETEC-blood group A interactions and stimulates adaptive immunity, we mutated EtpA, mapped its glycosylation by mass-spectrometry (MS), isolated polyclonal (pAbs) and monoclonal antibodies (mAbs) from vaccinated mice and ETEC-infected volunteers, and determined structures of antibody-EtpA complexes by cryo-electron microscopy. Both bgA and mAbs that inhibited EtpA-bgA interactions and ETEC adhesion, bound to the C-terminal repeat domain highlighting this region as crucial for ETEC pathogen-host interaction. MS analysis uncovered extensive and heterogeneous N-linked glycosylation of EtpA and cryo-EM structures revealed that mAbs directly engage these unique glycan containing epitopes. Finally, electron microscopy-based polyclonal epitope mapping revealed antibodies targeting numerous distinct epitopes on N and C-terminal domains, suggesting that EtpA vaccination generates responses against neutralizing and decoy regions of the molecule. Collectively, we anticipate that these data will inform our general understanding of pathogen-host glycan interactions and adaptive immunity relevant to rational vaccine subunit design.
Enterotoxigenic Escherichia coli (ETEC) infections are highly prevalent in developing countries, where clinical presentations range from asymptomatic colonization to severe cholera-like illness. The molecular basis for these varied presentations, which may involve strain-specific virulence features as well as host factors, has not been elucidated. We demonstrate that, when challenged with ETEC strain H10407, originally isolated from a case of cholera-like illness, blood group A human volunteers developed severe diarrhea more frequently than individuals from other blood groups. Interestingly, a diverse population of ETEC strains, including H10407, secrete the EtpA adhesin molecule. As many bacterial adhesins also agglutinate red blood cells, we combined the use of glycan arrays, biolayer inferometry, and noncanonical amino acid labeling with hemagglutination studies to demonstrate that EtpA is a dominant ETEC blood group A-specific lectin/hemagglutinin. Importantly, we have also shown that EtpA interacts specifically with glycans expressed on intestinal epithelial cells from blood group A individuals and that EtpA-mediated bacterial-host interactions accelerate bacterial adhesion and effective delivery of both the heat-labile and heat-stable toxins of ETEC. Collectively, these data provide additional insight into the complex molecular basis of severe ETEC diarrheal illness that may inform rational design of vaccines to protect those at highest risk.
Classical Approaches originated in the late of 19th Century and one of the oldest approaches; which represents traditional thoughts in management and based on the prototype industrial and military organization. The classical writers included Taylor, Fayol, Weber, Gullick, and Urwick, Mooney and Reiley and others and all they placed emphasis on work planning, the technical requirements, principles of management, formal structure, and the assumption of rational and logical behaviour, industrial management, including specialization, efficiency, higher quality, cost reduction and management-worker relationships. F.W. Taylor insisted on application of scientific methods to the problems of management. Henri Fayol suggested fourteen principles of management and their universal application. Max Weber introduced rationality in organisation, division of labour, specialization, structure, personnel competency, etc. Management is the study of managerial experiences. Classical treated organisation as a closed system. They ignored the element of human beings. Principles and functions of management have universal application. The study has been assessing the extent of applications of these theories in modern business scenario and analyzes relevance of these theories in organizations. The research paper is of descriptive in nature and assesses the impact of classical approaches on the current organizational practices. The study realized that organization must have to understand, accommodate, embrace and promote people dynamics to achieve production efficiency and effectively. Organizations should also review periodically their rules, regulations and manuals to ensure current trends in the business environment. Finally, that organization should allow for initiative, innovations and workers participation in decision making. The study evaluated current level of waste and labour turnover, layoff of workers, slow pace of growth and closure are caused by the application of the theories in management practice of the organizations.
Because O blood group has been associated with more severe cholera infections, it has been hypothesized that cholera toxin (CT) may bind non-O blood group antigens of the intestinal mucosae, thereby preventing efficient interaction with target GM1 gangliosides required for uptake of the toxin and activation of cyclic adenosine monophosphate (cAMP) signaling in target epithelia. Herein, we show that after exposure to CT, human enteroids expressing O blood group exhibited marked increase in cAMP relative to cells derived from blood group A individuals. Likewise, using CRISPR/Cas9 engineering, a functional group O line (HT-29-A(-/-)) was generated from a parent group A HT-29 line. CT stimulated robust cAMP responses in HT-29-A(-/-) cells relative to HT-29 cells. These findings provide a direct molecular link between blood group O expression and differential cellular responses to CT, recapitulating clinical and epidemiologic observations.
ABSTRACT At present, there is no vaccine for enterotoxigenic Escherichia coli (ETEC), an important cause of diarrheal illness. Nevertheless, recent microbial pathogenesis studies have identified a number of molecules produced by ETEC that contribute to its virulence and are novel antigenic targets to complement canonical vaccine approaches. EtpA is a secreted two-partner adhesin that is conserved within the ETEC pathovar. EtpA interacts with the tips of ETEC flagella to promote bacterial adhesion, toxin delivery, and intestinal colonization by forming molecular bridges between the bacteria and the epithelial surface. However, the nature of EtpA interactions with the intestinal epithelium remains poorly defined. Here, we demonstrate that EtpA interacts with glycans presented by transmembrane and secreted intestinal mucins at epithelial surfaces to facilitate pathogen-host interactions that culminate in toxin delivery. Moreover, we found that a major effector molecule of ETEC, the heat-labile enterotoxin (LT), may enhance these interactions by stimulating the production of the gel-forming mucin MUC2. Our studies suggest, however, that EtpA participates in complex and dynamic interactions between ETEC and the gastrointestinal mucosae in which host glycoproteins promote bacterial attachment while simultaneously limiting the epithelial engagement required for effective toxin delivery. Collectively, these data provide additional insight into the intricate nature of ETEC interactions with the intestinal epithelium that have potential implications for rational approaches to vaccine design.
The retail sector has strong impetus to overall economic growth as a significant driver of the growth of services sector, which contributes more than 50 per cent of GDP. It has strong backward and forward linkages with other sectors like agriculture and industry through stimulating demand for goods and through mass marketing, packaging, storage and transport. Moreover, it creates considerable direct and indirect employment in the economy. Also, the consumers have benefited in terms of wide range of products available in a market. The retail business in India is estimated at grow at 13 percent per annum from US$ 322 million in 2006-7 to US$ 590 billion in 2011–12 and expected to be US$ 700 billion in 2015–16. The unorganized sector is expected to grow at about 10 percent per annum from US$ 309 billion in 2006-7 to US$ 496 billion in 2011–12 and expected to be US$ 650 billion in 2015–16. Organized retail which now constitutes a small four percent of retail sector in 2006-7 is likely to grow at 45–50% per annum and quadruple its share of total retail trade to 16 percent by 2014–15. Retailing in India came with evolutionary patterns from grocery store to super market/malls. This sector was un-organized in the initial stage, and after that it is carried forward and now it is growing as supermarket and hypermarket. The paper depicts the main drivers of the retail revolution in India and how this revolution changes the buying behavior of the customer, increase in disposable income of the middle class, infrastructure development and changing customer choice. Organized Retailing is introduced in the last decade and has emerged as one of the sunrise industries in India. The survey intends to analyze the consumer behavior towards organized and unorganized retailing, their source of purchasing and the factors which influences their mall purchasing in India. The research paper intends to find out the consumer behavior towards organized (supermarkets/malls, hypermarkets, departmental stores etc) and unorganized (local grocery stores, weekly bazaars etc) retail stores in Delhi/NCR. The study focuses on the consumer's satisfaction level from organized retail stores as well as unorganized retail stores. This research paper is based on respondents who buy their product at organized and unorganized retail outlets. The study has tried to find out consumer behavior of respondents when they shop through organized and unorganized retail outlets. As a part of consumer behavior, their perceptions, motivation levels and demographic factors were studied. The study has also tried to study the reasons for preference of retail outlets and the attributes that consumers look for when they visit retail outlets.
Enterotoxigenic Escherichia coli (ETEC) is a major cause of morbidity and mortality due to infectious diarrhea in developing countries for which there is presently no effective vaccine. A central challenge in ETEC vaccinology has been the identification of conserved surface antigens to formulate a broadly protective vaccine. Here, we demonstrate that EatA, an immunogenic secreted serine protease of ETEC, contributes to virulence by degrading MUC2, the major protein present in the small intestinal mucous layer, and that removal of this barrier in vitro accelerates toxin access to the enterocyte surface. In addition, we demonstrate that vaccination with the recombinant secreted passenger domain of EatA (rEatAp) elicits high titers of antibody and is protective against intestinal infection with ETEC. These findings may have significant implications for development of both subunit and live-attenuated vaccines against ETEC and other enteric pathogens, including Shigella flexneri, that express similar proteins.
ABSTRACT The cryptococcal capsule is a critical virulence factor of an important pathogen, but little is known about how it is associated with the cell or released into the environment. Two mutants lacking PBX1 and PBX2 were found to shed reduced amounts of the capsule polysaccharide glucuronoxylomannan (GXM). Nuclear magnetic resonance, composition, and physical analyses showed that the shed material was of normal mass but was slightly enriched in xylose. In contrast to previous reports, this material contained no glucose. Notably, the capsule fibers of pbx Δ mutant cells grown under capsule-inducing conditions were present at a lower than usual density and were loosely attached to the cell wall. Mutant cell walls were also defective, as indicated by phenotypes including abnormal cell morphology, reduced mating filamentation, and altered cell integrity. All observed phenotypes were shared between the two mutants and exacerbated in a double mutant. Consistent with a role in surface glycan synthesis, the Pbx proteins localized to detergent-resistant membrane domains. These results, together with the sequence motifs in the Pbx proteins, suggest that Pbx1 and Pbx2 are redundant proteins that act in remodeling the cell wall to maintain normal cell morphology and precursor availability for other glycan synthetic processes. Their absence results in aberrant cell wall growth and metabolic imbalance, which together impact cell wall and capsule synthesis, cell morphology, and capsule association. The surface changes also lead to increased engulfment by host phagocytes, consistent with the lack of virulence of pbx mutants in animal models.
Article History: Received 14, March, 2015 Received in revised form 23, March, 2015 Accepted 13, April, 2015 Published online 28, April, 2015 In October 2013, the Indian cement industry had entered into the 100 years of its existence having, inter alia, state of art technology and world class cement production. Since its inception the Indian cement industry have been gone through the various types of technological changes. Organizational Development is a field of applied behavioural science related to planned change. The basic objective of change is the total organizational and its system. Organizational Development is a newly emerging discipline directed towards using behavioural science knowledge to assist organization in solving problems and dealing more rapidly with the problem of change. Change is the essence of business growth. The external pressures are driving change at an alarming rate and affecting every aspect of organization. Identifying environmental and market changes quickly is a part of survival and growth. This present paper have been analyzed a revolutionary change occurring in technology in cement industry in India, where new and improved methods need to be developed to deal with such changes. Leavitt describes a model of the major targets of changes, which lead to the resolution of three major problems. Changes in these variables cause alterations in organizational behaviour, which is crucial to survival: technology, structure and people. This paper presents the technological development and changes in cement industry in India. This paper studies the impact of technological changes on organizational growth and analyzing the technological changes in India Cement Industry.
Enterotoxigenic Escherichia coli (ETEC) strains are among the most common causes of diarrheal illness worldwide. These pathogens disproportionately afflict children in developing countries, where they cause substantial morbidity and are responsible for hundreds of thousands of deaths each year. Although these organisms are important targets for enteric vaccines, most development efforts to date have centered on a subset of plasmid-encoded fimbrial adhesins known as colonization factors and heatlabile toxin (LT). Emerging data suggest that ETEC undergoes considerable changes in its surface architecture, sequentially deploying a number of putative adhesins during its interactions with the host. We demonstrate here that one putative highly conserved, chromosomally encoded adhesin, EaeH, engages the surfaces of intestinal epithelial cells and contributes to bacterial adhesion, LT delivery, and colonization of the small intestine.
ABSTRACT Enterotoxigenic Escherichia coli (ETEC) is a leading cause of death due to diarrheal illness among young children in developing countries, and there is currently no effective vaccine. Many elements of ETEC pathogenesis are still poorly defined. Here we demonstrate that YghJ, a secreted ETEC antigen identified in immunoproteomic studies using convalescent patient sera, is required for efficient access to small intestinal enterocytes and for the optimal delivery of heat-labile toxin (LT). Furthermore, YghJ is a highly conserved metalloprotease that influences intestinal colonization of ETEC by degrading the major mucins in the small intestine, MUC2 and MUC3. Genes encoding YghJ and its cognate type II secretion system (T2SS), which also secretes LT, are highly conserved in ETEC and exist in other enteric pathogens, including other diarrheagenic E. coli and Vibrio cholerae bacteria, suggesting that this mucin-degrading enzyme may represent a shared virulence feature of these important pathogens.
Recently, the growth of the Indian economy after starting of liberalization and globalisation policy in 1991 hasbeen substantial increase in the purchasing power of the rural habitants. Since Green revolution in India, the ruralareas are started to use a large quantity of consumable and non-consumable products. In this way, ruralmarketing has been used as a strategy to combat against the competition by the marketers. The rural marketingand agricultural marketing prior to globalisation of Indian economy convey the same meaning, but after wardsboth understand by the markets in different context– the later denotes agricultural and rural production of the forthe urban consumers or industrial consumers, whereas rural marketing involves marketing of manufactured orprocessed inputs to rural consumers. These have changed the entire spectrum of marketing for the Indian ruralmarket and force the marketers to move towards rural areas. Rural marketing in India is still at infancy stages,and faces the various types of problems in respect of marketing, product designing and positioning, pricing,distribution and promotion. Today’s corporation must understand the rural market on different context to widentheir business horizon, to expand their market and to exploiting the opportunities available in the rural areas. TheIndian rural market is bigger and vast in size with its lager consumer base, its offers the great opportunities forthe marketer and stay tune with the rural marketing offerings. Rural marketing consists of around 833 millionpotential consumers, and majority of the Indian middle-class, and about half the country's disposable income.The marketer must understand the growing complexities of the rural market and making strategy for the propermixing of marketing mix. It involves high risk and attractive for those who are searching challenge and having acourage to face those challenges. The key to face the challenges is to understand the market, the consumer needand behaviour.Hence, it is proposed to undertake in this study to assess the various dimension of Indian rural markets. The mainaim of this study is to observe the potentiality of Indian Rural Markets and finding out various problems arebeing faced by rural markets. This paper attempts to look into the challenges and opportunities of Indian ruralmarketing by adopting SWOT analysis matrix on rural markets.
Cryptococcus neoformans, a basidiomycete yeast and opportunistic pathogen, expends significant biosynthetic effort on construction of a polysaccharide capsule with a radius that may be many times that of the cell. Beyond posing a stimulating challenge in terms of defining biosynthetic pathways, the capsule is required for this yeast to cause fatal disease. This combination has focused the attention of researchers on this system. Here we briefly review two aspects of the rapidly advancing field of capsule synthesis: the extensive variation that occurs in capsule polymers and the regulation of capsule biosynthesis.