Dichotomous Role Research Articles

Regulation of Store-Operated Ca2+ Entry by SARAF.

Calcium (Ca2+) signaling plays a dichotomous role in cellular biology, controlling cell survival and proliferation on the one hand and cellular toxicity and cell death on the other. Store-operated Ca2+ entry (SOCE) by CRAC channels represents a major pathway for Ca2+ entry in non-excitable cells. The CRAC channel has two key components, the endoplasmic reticulum Ca2+ sensor stromal interaction molecule (STIM) and the plasma-membrane Ca2+ channel Orai. Physical coupling between STIM and Orai opens the CRAC channel and the resulting Ca2+ flux is regulated by a negative feedback mechanism of slow Ca2+ dependent inactivation (SCDI). The identification of the SOCE-associated regulatory factor (SARAF) and investigations of its role in SCDI have led to new functional and molecular insights into how SOCE is controlled. In this review, we provide an overview of the functional and molecular mechanisms underlying SCDI and discuss how the interaction between SARAF, STIM1, and Orai1 shapes Ca2+ signaling in cells.

A new cytokine target for chronic obstructive pulmonary disease?

A new cytokine target for chronic obstructive pulmonary disease?

Abstract 114: Loss of BMPR1a in fibroblasts restricts breast cancer progression and alters the immune tumor microenvironment

Abstract The Bone Morphogenetic Protein (BMP) pathway is a member of the TGFβ signaling family and has complex roles in cancer. The dichotomous role of BMPs as both tumor promoters and suppressors appears to be largely context based in both the cancer cell and the surrounding microenvironment. Fibroblasts who are activated in the tumor microenvironment to become cancer associated fibroblasts (CAFs) also carry out diverse functions to support tumor progression, including matrix generation and remodeling as well as angiogenesis and immune cell regulation. We found that conditional deletion of the BMP signaling receptor BMPR1a in mammary fat pad derived fibroblasts (via FSP-Cre) restricts tumor progression in a C57BL/6 syngeneic mammary fat pad MMTV-PyMT breast cancer mouse model. Specific changes in the architecture of collagen were found in the tumors with loss of BMPR1a signaling in CAFs. We analyzed these mammary fat pad tumors using Vectra multiplexed immunohistochemistry (mIHC) to evaluate differential cell phenotypes, spatial distribution, and high-dimensional cell clustering dependent on BMP signaling in CAFs. Vectra mIHC panels were designed to perform tumor and stromal cell classification, immune cell profiling, immune cell function, cell signaling and vascular analysis. Based on Vectra mIHC, changes in myeloid cell populations and immune cell interactions in the tumors were observed with differential BMPR1a expression in CAFs. We profiled the secretome of mammary fat pad fibroblasts and found distinct chemokine and cytokine secretion was altered related on BMPR1a loss. These results indicate a unique necessity for BMP signaling in fibroblasts during tumor progression to influence the stroma, matrix, and immune components of the tumor microenvironment. Citation Format: Claire Louise Ihle, Meredith D. Provera, Parvanee A. Karimpour, Desiree M. Straign, Erin Smith, Philip Owens. Loss of BMPR1a in fibroblasts restricts breast cancer progression and alters the immune tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 114.

낭만주의와 여성의 시민권: 젠더와 문화, 공동체 의식

This study aims to explore how women’s citizenship against patriarchy and gender inequality is reflected in the works of Romanticism. The principal element is to analyze gender, culture and community spirit in the works of the Romantic writers Mary Wollstonecraft, William Blake, Anna Barbauld, and Amelia Opie. As radicals, all of them wanted to pursue women’s citizenship against the stereotyped gender roles amid the revolutionary period. Wollstonecraft enthusiastically attempted to get the gender equality of female social roles. Blake attempted to recover gender identity against dichotomous gender roles through his protagonist Thel and Oothoon. Barbauld prophesied of the British empire’s end and Opie desired a peaceful community without racial discrimination. It is impossibility to appreciate the hope of women achieving citizenship without approaching the new values of race, class, and gender in British Romanticism.

Risk perception as a double-edged sword in policy compliance in COVID-19 pandemic? A two-phase evaluation from Hong Kong

The emphasis of risk has been recognized as a crucial component to effective and successful policy compliance amidst a crisis. Yet, during the COVID-19 pandemic, when the impact of risk may fluctuate with the severity of the prolonged pandemic, and that the public consider not only public health factors when they choose but also whether to follow a COVID-19-related policy, perceived risk may not always lead to policy compliance. Two cross-sectional online surveys (during almost zero case period in late April to May, 2020 (Wave 2) and during the biggest outbreak in July, 2020 (Wave 3)) with convenient sampling were conducted to examine the dichotomous role of perceived severity and perceived susceptibility in influencing policy compliance in Hong Kong. A total of 1816 responses from local adults were collected (Wave 2: N = 564; Female % = 69.7%; Mean age = 39.4; Wave 3: N = 1252; Female %=68.8%; Mean age = 40.2). Although policy compliance is found to increase with the scale of the outbreak, results from path analyses showed that perceived susceptibility and perceived severity have an indirect role in policy complying behaviour when the objective risk is low. Risk variables, including attitude, knowledge, benefit and trust, have directly shaped policy compliance. More importantly, perceived severity boosts policy compliance but perceived susceptibility was associated with disobedience to public health policies. Meanwhile, Hong Kong citizens have a selective and conscious preference regarding the stringency of public health policy: They welcome more law and order, with increasing magnitude of penalty, but reject lockdown measures such as a curfew. Regression results implied that demography had a mild contribution to the acceptance of public health policies, with only the female gender being statistically related to higher policy acceptance. The findings of this study imply that boosting attitude, knowledge, benefit and trust would come more directly helpful in promoting public health policy compliance than emphasizing on risks alone. This study calls for further reflection on the traditional role of risk, especially perceived susceptibility, in mobilizing policy compliance to COVID-19-related measures.

Active autophagy in cancer-associated fibroblasts: Recent advances in understanding the novel mechanism of tumor progression and therapeutic response.

Autophagy is primarily a homeostatic and catabolic process that is increasingly being recognized to have a pivotal role in the initiation and maintenance of cancer cells, as well as in the emergence of therapeutic resistance. Moreover, in the tumor microenvironment (TME) autophagy plays a crucial and sometimes dichotomous role in tumor progression. Recent studies show that during the early stages of tumor initiation, autophagy suppresses tumorigenesis. However, in the advanced stage of tumorigenesis, autophagy promotes cancer progression by protecting cancer cells against stressful conditions and therapeutic assault. Specifically, in cancer-associated fibroblasts (CAFs), autophagy promotes tumorigenesis not only by providing nutrients to the cancerous cells but also by inducing epithelial to mesenchymal transition, angiogenesis, stemness, and metastatic dissemination of the cancer cells, whereas in the immune cells, autophagy induces the tumor-localized immune response. In the TME, CAFs play a crucial role in cancer cell metabolism, immunoreaction, and growth. Therefore, targeting autophagy in CAFs by several pharmacological inducers like rapamycin or the inhibitor such as chloroquine has gained importance in preclinical and clinical trials. In the present review, we summarized the basic mechanism of autophagy in CAFs along with its role in driving tumorigenic progression through several emerging as well as classical hallmarks of cancer. We also addressed various autophagy inducers as well as inhibitors of autophagy for more efficient cancer management. Eventually, we prioritized some of the outstanding issues that must be addressed with utmost priority in the future to elucidate the role of autophagy in CAFs on tumor progression and therapeutic intervention.

Function of circulating myeloid cells in healthy donors and patients with metastatic solid tumors

Abstract Monocytes are a heterogeneous group of mononuclear innate immune cells that have diverse inflammatory responses. In the context of cancer, monocytes and monocyte-derived cells have been evaluated for their pro- and anti-tumoral effects in the tumor microenvironment. These functions range from induction of tumor cell death to suppression of T cells, promotion of angiogenesis and remodeling of the extracellular matrix. Outside of the primary tumor, monocytes in circulation maintain their dichotomous role in cancer immunosurveillance. Specifically, patrolling non-classical CD14−CD16+ monocytes have been found to play a role in the prevention of metastasis. In contrast, CD14+ monocyte-derived cells from patients with solid tumors have been shown to promote tumor progression. Therefore, understanding this monocytic heterogeneity as well as other unexplored roles (i.e. monocyte-mediated phagocytosis of tumor cells) is crucially important for malignancies with high rates of metastasis. Yet, the phenotypic and functional diversity of circulating monocytes in patients with metastatic solid malignancies is still largely unknown. In this study, we sought to characterize and compare peripheral blood monocytes obtained from healthy donors and patients with advanced stage solid tumors. Through flow cytometric analysis and functional assays, we determined the subpopulation distributions as well as the phagocytic and suppressive activities of the monocytic compartment in patients with advanced cancer and healthy controls. Providing new insights into their cancer-related functions, we highlight the need for consideration of circulating monocytes into immune-targeting approaches in metastatic solid malignancies.

19P A dichotomous oncogenic role of the splicing factor SF3A3 in MYC-driven triple-negative breast cancer

Splicing is a central RNA-based process commonly altered in human cancers; however, how spliceosomal components are co-opted during tumorigenesis remains poorly defined. Previous work on MYC-driven triple negative breast cancer (TNBC) has revealed the spliceasome as an essential vulnerability that can be targeted to achieve disease control. Therefore, an important outstanding question is the contribution of individual components of the spliceosome machinery to the tumorigenic process downstream of MYC hyperactivation.

Sodium chloride generates anti-inflammatory Th17 cell responses but amplifies Th17 cell pathogenicity in pro-inflammatory cytokine microenvironments

Abstract Ionic signals have recently been demonstrated to affect T cell polarization and function. Sodium chloride (NaCl) was proposed to accumulate in peripheral tissues upon dietary intake and to promote autoimmunity via the Th17 cell axis. We here demonstrate that together with amplification of human Th17 cell signature properties, NaCl gave rise to a stable anti-inflammatory Th17 cell fate that we found to be restricted to distinct pathogen specificities. The p38/MAPK pathway involving NFAT5 and SGK1regulated FoxP3 and IL-17 expression in high NaCl conditions. The NaCl induced acquisition of an anti-inflammatory Th17 cell fate was confirmed in vivo in the mouse model of experimental autoimmune encephalomyelitis (EAE), which demonstrated strongly reduced disease symptoms upon transfer of NaCl-treated encephalitogenic Th17 cells. However, NaCl was coopted to promote murine and human Th17 cell pathogenicity, if T cell stimulation occurred in a proinflammatory and TGF-b low cytokine microenvironment. This revealed a context dependent dichotomous role for NaCl in shaping the pathogenicity of Th17 cells. NaCl might therefore prove beneficial for the treatment of chronic inflammatory diseases in collaboration with cytokine blocking drugs.

IL-33trap-mediated IL-33 neutralization does not exacerbate choroidal neovascularization, but fails to protect against retinal degeneration in a dry age-related macular degeneration model

The progressive and sight-threatening disease, age-related macular degeneration (AMD), is a growing public health concern due to ageing demographics, with the highest unmet medical need for the advanced stage of dry AMD, geographic atrophy. The pathogenesis underlying AMD is driven by a complex interplay of genetic and environmental factors. There is ample evidence that inflammation is strongly involved in AMD development. Interleukin-33 (IL-33) has been proposed to be critically involved in retinal degeneration, but a protective role in eye pathophysiology was also demonstrated. The current study investigated the therapeutic potential of IL-33trap, a novel IL-33-neutralizing biologic, in dry AMD/geographic atrophy and, based on controversial data regarding the protective versus detrimental functions of IL-33 in neovascularization, evaluated the risk of progression to wet AMD by IL-33 neutralization. Repeated intravitreal (IVT) injections of IL-33trap in the mouse laser-induced choroidal neovascularization model did not exacerbate neovascularization or leakage, while it significantly inhibited inflammatory cell infiltration in the retinal pigment epithelium and choroid. On the contrary, IVT treatment with IL-33trap significantly induced retinal inflammation and could not prevent retinopathy induction in the mouse sodium iodate (NaIO3) model. Overall, these data suggest a complex and dichotomous role of IL-33 in eye pathology and indicate that IL-33 neutralization is not able to prevent onset and progression of dry AMD pathogenesis.

Novel Immune Subsets and Related Cytokines: Emerging Players in the Progression of Liver Fibrosis.

Liver fibrosis is a pathological process caused by persistent chronic injury of the liver. Kupffer cells, natural killer (NK) cells, NKT cells, and dendritic cells (DCs), which are in close contact with T and B cells, serve to bridge innate and adaptive immunity in the liver. Meanwhile, an imbalanced inflammatory response constitutes a challenge in liver disease. The dichotomous roles of novel immune cells, including T helper 17 (Th17), regulatory T cells (Tregs), mucosa-associated invariant T cells (MAIT), and innate lymphoid cells (ILCs) in liver fibrosis have gradually been revealed. These cells not only induce damage during liver fibrosis but also promote tissue repair. Hence, immune cells have unique, and often opposing, roles during the various stages of fibrosis. Due to this heterogeneity, the treatment, or reversal of fibrosis through the target of immune cells have attracted much attention. Moreover, activation of hepatic stellate cells (HSCs) constitutes the core of fibrosis. This activation is regulated by various immune mediators, including Th17, Th22, and Th9, MAIT, ILCs, and γδ T cells, as well as their related cytokines. Thus, liver fibrosis results from the complex interaction of these immune mediators, thereby complicating the ability to elucidate the mechanisms of action elicited by each cell type. Future developments in biotechnology will certainly aid in this feat to inform the design of novel therapeutic targets. Therefore, the aim of this review was to summarize the role of specific immune cells in liver fibrosis, as well as biomarkers and treatment methods related to these cells.

Soil microorganisms decrease barley biomass uniformly across contrasting nitrogen availability

AimsMicroorganisms play a dichotomous role in the soil nitrogen cycle through mineralization and immobilization. We aimed to understand how nitrogen availability modifies the effect of microorganisms on plant growth. We hypothesized that soil microorganisms would increase plant biomass following amendment with a substrate rich in organic nitrogen (net mineralization), be neutral when adding inorganic nitrogen, and decrease biomass when adding organic nitrogen-limited substrate (nitrogen competition). MethodBarley (Hordeum vulgare L., cv. Evergreen) was exposed to either i) limited, organically bound nitrogen, ii) organically bound nitrogen or iii) inorganic nitrogen. In these amendments, we assessed the differences in plant biomass and physiology between plants with or without soil microbiome addition. ResultsThe soil microbiome reduced shoot biomass equally (12%) across all nitrogen amendments. However, nitrogen availability did modulate the effect of the soil microbiome on plant physiological parameters associated with nitrogen deficiency. ConclusionsThe results indicate that the net negative effect of complex microbiomes on shoot biomass is independent of nitrogen availability. Thus, microbiome addition was deleterious to biomass even in a nutrient-stress-free environment. We suggest that strategies for improving plant growth through manipulation of microorganisms should not exclusively focus on beneficial and pathogenic microorganisms, but also include minimizing plant metabolic costs of microbiome interactions.

Abstract IA010: How opposing roles of interferon and pattern recognition receptor signaling in the TME influence immunotherapy

Abstract Interferon (IFN) signaling pathways are broadly active across multiple cancer types. These pathways are typically associated with pathogen infection, but their roles in cancer are less understood. Emerging evidence indicates that IFN signaling has complex and even dichotomous roles in both cancer and host-pathogen interactions. On the one hand, IFN is often essential for immune activation and for promoting response to cancer immunotherapies. On the other hand, prolonged IFN signaling that accompanies persistent disease can lead to immunotherapy resistance and immunosuppression. This latter role represents a feedback inhibition mechanism that can also be observed in chronic pathogen infections to limit immune-mediated pathology. Thus, how these opposing effects of IFN signaling are controlled and what factors dictate one function over the other are important questions. In this presentation, insight into how opposing functions of IFN and pattern recognition receptor signaling impact cancer immunotherapy will be discussed. This will include evidence for what factors might favor one function of IFN over the other. Finally, work will be presented that illustrates how key interferon-stimulated genes (ISGs) expressed by cancer cells can control whether an immune stimulatory or suppressive tumor immune microenvironment develops. Citation Format: Andy J. Minn. How opposing roles of interferon and pattern recognition receptor signaling in the TME influence immunotherapy [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr IA010.

Abstract IA009: Dact1 biomolecular condensates mediate TGFβ-Wnt crosstalk in bone metastasis

Abstract TGF-β signaling is a well established pathway driving different steps of bone metastasis progression. Wnt signaling plays a dichotomous role in bone metastasis, with recent studies showing that inhibition of Wnt signaling by DKK1 is critical for avoidance of immune clearance of dormant bone micrometastasis and activation of osteoclast activity during osteolytic outgrowth. On the other hand, engagement of bone vascular E-selectin by disseminated tumor cells (DTCs) promotes metastatic colonization in bone by activating Wnt signaling to enhance tumor initiating activity of DTCs. These findings imply a complex interplay between TGF-b and Wnt signaling in different stages of bone metastasis development that allows efficient colonization, dormancy and outgrowth of secondary tumors in bone. What mediates the dynamic transition of TGF-β and Wnt signaling states during metastasis is currently unknown. Here we present data describing a novel phase-separated organelle organized by bone metastasis promoting protein Dact1 which mediates the crosstalk of TGF-β and Wnt signaling. We found that Dact1 is induced by TGF-β signaling and forms dynamically regulated biomolecular condensates that suppress Wnt signaling. A high level of Dact1 expression is associated with an elevated risk of bone metastasis in breast cancer patients and Dact1 is necessary for bone metastasis in mouse models of breast and prostate cancers. Citation Format: Yibin Kang. Dact1 biomolecular condensates mediate TGFβ-Wnt crosstalk in bone metastasis [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr IA009.

The functions of autophagy at the tumour-immune interface.

Autophagy is frequently induced in the hypoxic tumour microenvironment. Accumulating evidence reveals important functions of autophagy at the tumour‐immune interface. Herein, we propose an update on the roles of autophagy in modulating tumour immunity. Autophagy promotes adaptive resistance of established tumours to the cytotoxic effects of natural killer cells (NKs), macrophages and effector T cells. Increased autophagic flux in tumours dampen their immunogenicity and inhibits the expansion of cytotoxic T lymphocytes (CTLs) by suppressing the activation of STING type I interferon signalling (IFN‐I) innate immune sensing pathway. Autophagy in suppressive tumour‐infiltrating immune subsets maintains their survival through metabolic remodelling. On the other hand, autophagy is involved in the antigen processing and presentation process, which is essential for anti‐tumour immune responses. Genetic deletion of autophagy induces spontaneous tumours in some models. Thus, the role of autophagy is context‐dependent. In summary, our review has revealed the dichotomous roles of autophagy in modulating tumour immunity. Broad targeting of autophagy may not yield maximal benefits. The characterization of specific genes regulating tumour immunogenicity and innovation in targeted delivery of autophagy inhibitors into certain tumours are among the most urgent tasks to sensitize cold cancers to immunotherapy.

Cell Cycle Regulation of the Pdx1 Transcription Factor in Developing Pancreas and Insulin-Producing β-Cells.

Current evidence indicates that proliferating β-cells express lower levels of some functional cell identity genes, suggesting that proliferating cells are not optimally functional. Pdx1 is important for β-cell specification, function, and proliferation and is mutated in monogenic forms of diabetes. However, its regulation during the cell cycle is unknown. Here we examined Pdx1 protein expression in immortalized β-cells, maternal mouse islets during pregnancy, and mouse embryonic pancreas. We demonstrate that Pdx1 localization and protein levels are highly dynamic. In nonmitotic cells, Pdx1 is not observed in constitutive heterochromatin, nucleoli, or most areas containing repressive epigenetic marks. At prophase, Pdx1 is enriched around the chromosomes before Ki67 coating of the chromosome surface. Pdx1 uniformly localizes in the cytoplasm at prometaphase and becomes enriched around the chromosomes again at the end of cell division, before nuclear envelope formation. Cells in S phase have lower Pdx1 levels than cells at earlier cell cycle stages, and overexpression of Pdx1 in INS-1 cells prevents progression toward G2, suggesting that cell cycle-dependent regulation of Pdx1 is required for completion of mitosis. Together, we find that Pdx1 localization and protein levels are tightly regulated throughout the cell cycle. This dynamic regulation has implications for the dichotomous role of Pdx1 in β-cell function and proliferation.

Examining the Adoption of Onlineto- Offline (O2O)

The online-to-offline (O2O) business model is rapidly growing among organizations, yet current knowledge on O2O adoption is predominantly individual focused, with little research on organizational adoption and the factors driving adoption. To address this gap, underpinned by the diffusion of innovation (DOI) theory, this study collected qualitative data (24 semistructured interviews), which were analyzed using content analysis techniques. We found that offline service quality and social network prosperity are some of the factors driving O2O adoption. Surprisingly, inefficient offline marketing was also found to drive O2O adoption, which indicates new challenges posed by the growing online business environment. We found that not all factors can be categorically classified as facilitating or impeding adoption, as some factors (such as operational challenges and costs) could play dichotomous roles of facilitating or impeding in the context of peculiar circumstances. For example, we found cost to be an impeding factor, yet the results also indicated the benefits of cost reduction resulting from O2O adoption, thereby rendering cost a contentious issue. This study extends the application of DOI theory to the O2O adoption stage, and identifies a number of new factors associated with internal/external organizational characteristics, as postulated in the DOI. Managerial implications are discussed.

Gut Commensal-Induced IκBζ Expression in Dendritic Cells Influences the Th17 Response.

Intestinal commensal bacteria can have a large impact on the state of health and disease of the host. Regulation of Th17 cell development by gut commensals is known to contribute to their dichotomous role in promoting gut homeostasis and host defense, or development of autoimmune diseases. Yet, the underlying mechanisms remain to be fully elucidated. One candidate factor contributing to Th17 differentiation, and the expression of which could be influenced by commensals is the atypical nuclear IκB protein IκBζ. IκBζ acts as a transcriptional regulator of the expression of Th17-related secondary response genes in many cell types including dendritic cells (DCs). Insights into the regulation of IκBζ in DCs could shed light on how these immune sentinel cells at the interface between commensals, innate and adaptive immune system drive an immune-tolerogenic or inflammatory Th17 cell response. In this study, the influence of two gut commensals of low (Bacteroides vulgatus) or high (Escherichia coli) immunogenicity on IκBζ expression in DCs and its downstream effects was analyzed. We observed that the amount of IκBζ expression and secretion of Th17-inducing cytokines correlated with the immunogenicity of these commensals. However, under immune-balanced conditions, E. coli also strongly induced an IκBζ-dependent secretion of anti-inflammatory IL-10, facilitating a counter-regulative Treg response as assessed in in vitro CD4+ T cell polarization assays. Yet, in an in vivo mouse model of T cell-induced colitis, prone to inflammatory and autoimmune conditions, administration of E. coli promoted an expansion of rather pro-inflammatory T helper cell subsets whereas administration of B. vulgatus resulted in the induction of protective T helper cell subsets. These findings might contribute to the development of new therapeutic strategies for the treatment of autoimmune diseases using commensals or commensal-derived components.

Enactment of Gender and Performing Selves: A Study on Hijra Performativity

ABSTRACT ‘Sex' is understood as ‘anatomically' and ‘biologically’ inherent in an individual and is mirrored through 'gender' and its signifiers. The contested binaries of male and female are associated with the perceptions of an individual's level of conformity to the vexed ideals of ‘masculinity' and ‘femininity', but a ‘trans' identity finds its expression outside these assigned gender dichotomous roles and find its expression in embodied and bodied practices. The aspects of masculinity and femininity are seen as ‘performative' which can be reflected through ‘sign vehicle' and ‘body idiom', the terms used by Sociologist Erving Goffman. Based on the Butlerian theory of ‘performativity of gender' and ‘materialization', this study pursues the question of hijra (trans woman) construction through the conceptual framework of ‘performance', ‘corporeal significations' and ‘appearance' which is linked to their gendered identity. The reading examines and critiques on the construction of hijra identity and further observes that in imitating the inveterate femininity their construction goes beyond the ascribed ‘feminine’ gender role. It engages with select hijra autobiographies namely, The Truth About Me (2010) by A Revathi, I Am Vidya (2007) by Vidya and Me Hijra, Me Laxmi (2015) by Laxmi, which provides narratives on distinct construction of hijra feminine identity.

A Framework Analysis for Lean Transformation: A Case Study of a Public Utility in Greece

Purpose: Nowadays, the worldwide economic recession has created numerous challenges in the Public Sector of Greece, which in turn affect the sustainability of public enterprises. Overall, there is a high pressure to increase productivity and reduce operating costs. The need to adapt to the new environment is pushing public organizations to implement Lean Management strategies in accordance with Private Sector standards. However, the limited budget, public deficits and debts, bureaucratic culture, political dependence and lack of transparency present several issues. These pose a serious threat to successful implementation of Lean practices in the long-run. Lack of relevant research and dichotomous role of public service organizations make this study very interesting. This research paper is aiming at exploring and highlighting the impact of the most important Critical Success Factors (CSFs) for the effective integration of Lean Management principles in Public Utility organizations in Greece by combining bibliographic research and empirical—with the quantitative method-research through case studies. Research Methodology: The research method combines bibliographic research and empirical—with the quantitative method. Quantitative method was employed on a sufficient sample of public employees from two of the largest public companies of Greece: Public Power Corporation (PPC S.A.) and Athens Water Supply and Sewerage Company (EYDAP S.A.) in order to investigate the impact of the most important CSFs on successful Lean Transformation of them. Findings: Quantitative findings from this research illustrated that the most important CSFs that have a positive impact on successful Lean Transformation on Greek public organizations/utilities are: Effective Communication, flexible Organizational Infrastructure, Customer Focus, Linking Lean to Suppliers, Business Plan and Vision, competent Change Management, Top Management Support and Commitment, Training and Education, as well as Selection of Staff. On the contrary, the existence of a bureaucratic Organizational Culture has a negative effect on successful integration of Lean Management. Limitations: Important limitations of this study are the utilization of a convenience sample and the strict focus on Greek public organizations operating in a competitive environment.