scholarly journals Trypanosoma cruzi Bromodomain Factor 3 Binds Acetylated α-Tubulin and Concentrates in the Flagellum during Metacyclogenesis

2014 ◽  
Vol 13 (6) ◽  
pp. 822-831 ◽  
Author(s):  
Victoria Lucia Alonso ◽  
Gabriela Vanina Villanova ◽  
Carla Ritagliati ◽  
María Cristina Machado Motta ◽  
Pamela Cribb ◽  
...  
Keyword(s):  
Life Cycle ◽  
Trypanosoma Cruzi ◽  
Western Blot ◽  
Posttranslational Modifications ◽  
Fluorescent Protein ◽  
Flagellar Pocket ◽  
Content Type ◽  
Binding Domains ◽  
Life Cycle Stages ◽  
Far Western Blot

ABSTRACTBromodomains are highly conserved acetyl-lysine binding domains found mainly in proteins associated with chromatin and nuclear acetyltransferases. TheTrypanosoma cruzigenome encodes at least four bromodomain factors (TcBDFs). We describe here bromodomain factor 3 (TcBDF3), a bromodomain-containing protein localized in the cytoplasm.TcBDF3 cytolocalization was determined, using purified antibodies, by Western blot and immunofluorescence analyses in all life cycle stages ofT. cruzi. In epimastigotes and amastigotes, it was detected in the cytoplasm, the flagellum, and the flagellar pocket, and in trypomastigotes only in the flagellum. Subcellular localization ofTcBDF3 was also determined by digitonin extraction, ultrastructural immunocytochemistry, and expression ofTcBDF3 fused to cyan fluorescent protein (CFP). Tubulin can acquire different posttranslational modifications, which modulate microtubule functions. Acetylated α-tubulin has been found in the axonemes of flagella and cilia, as well as in the subpellicular microtubules of trypanosomatids.TcBDF3 and acetylated α-tubulin partially colocalized in isolated cytoskeletons and flagella fromT. cruziepimastigotes and trypomastigotes. Interaction between the two proteins was confirmed by coimmunoprecipitation and far-Western blot assays with synthetic acetylated α-tubulin peptides and recombinantTcBDF3.

scholarly journals Organisational learning and the organisational life cycle

2016 ◽  
Vol 40 (1) ◽  
pp. 2-20 ◽  
Author(s):  
Steven Tam ◽  
David E Gray
Keyword(s):  
Life Cycle ◽  
Human Resource Development ◽  
Learning Strategies ◽  
High Growth ◽  
Organisational Learning ◽  
Structured Interviews ◽  
Content Type ◽  
Life Cycle Stages ◽  
Timely Fashion ◽  
Sound Foundation

Purpose – The purpose of this study is to relate the practice of organisational learning in small- and medium-sized enterprises (SMEs) to the organisational life cycle (OLC), contextualising the differential aspects of an integrated relationship between them. Design/methodology/approach – It is a mixed-method study with two consecutive phases. In Phase I, 30 Hong Kong SMEs identified through theoretical sampling were classified into three life-cycle stages – inception, high growth and maturity. In Phase II, their employees’ learning practices (grouped by learning levels) were statistically compared using the analysis of variance and then followed up for confirmation with qualitative semi-structured interviews. Findings – This study uniquely suggests the nature of a relationship between SME organisational learning and the OLC. Empirical results show that three of the four learning levels (individual, group, organisational and inter-organisational) practised in SMEs are varied in importance between life-cycle stages. Research limitations/implications – Comparative studies are encouraged in other parts of the world to strengthen the findings – with either SMEs or large organisations. Practical implications – The study informs SME owner/managers about what is important for employee learning at different business stages so that appropriate learning strategies or human resource development policies can be formulated in a timely fashion to promote competitiveness. Originality/value – It is among the first studies to connect SME learning with organisational growth. The relationships found serve as a sound foundation for further empirical investigations.

Is there a decision to make, boss? From understanding SME growth to managing employees' learning preferences

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Steven Tam ◽  
David E. Gray
Keyword(s):  
Life Cycle ◽  
High Growth ◽  
Life Cycle Stage ◽  
Learning Preferences ◽  
Best Interests ◽  
Structured Interviews ◽  
Managerial Decision ◽  
Content Type ◽  
Learning Practices ◽  
Life Cycle Stages

PurposeThis study examines employees' learning preferences in small and medium-sized enterprises (SMEs) at different life-cycle stages.Design/methodology/approachThe study has two phases. Phase I classified a sample of 30 Hong Kong SMEs into three different life-cycle stages (inception, high growth or maturity). Phase II then explored/compared their employees' learning practices in terms of importance using a mixed-method design through an online learning questionnaire followed by face-to-face semi-structured interviews.FindingsBased on a list of 32 learning practices common to SME workplaces, the study identified how SME employees perceive the importance of a learning practice. The top 5 and the bottom 5 learning practices in SMEs across life-cycle stages are presented to promote best interests for SME executives.Research limitations/implicationsWhile SME learning is highly varied, this study sheds light on some traceable context about it as an SME grows. Similar studies with additional SMEs, including SMEs in other locations, are encouraged to strengthen the findings.Practical implicationsThe findings help SME executives understand what learning practices are most important (or least important) for their employees, given the life-cycle stage of the firm. Aligning a business with employees' learning preferences in a timely fashion is a managerial decision to be made for driving organizational effectiveness.Originality/valueIt is among the first studies connecting employee learning in SMEs and organizational life cycle to address a critical but missing inquiry.

IFRS adoption, financial reporting quality and cost of capital: a life cycle perspective

2019 ◽  
Vol 31 (3) ◽  
pp. 497-522 ◽  
Author(s):  
Ahsan Habib ◽  
Md. Borhan Uddin Bhuiyan ◽  
Mostafa Monzur Hasan
Keyword(s):  
Life Cycle ◽  
Financial Reporting ◽  
Cost Of Capital ◽  
Reporting Quality ◽  
Financial Reporting Quality ◽  
Cost Of Equity ◽  
Content Type ◽  
Ifrs Adoption ◽  
Life Cycle Stages ◽  
The Impact

Purpose This paper aims to investigate the impact of International Financial Reporting Standards (IFRS) adoption on financial reporting quality and cost of equity. The paper further investigates whether such association varies at different life cycle stages. Design/methodology/approach This paper follows the methodologies of DeAngelo et al. (2006) and Dickinson (2011) to develop proxies for the firms’ stages in the life cycle. Findings Using both pre- and post-IFRS adoption period for Australian listed companies, the paper finds that financial reporting quality reduced and cost of equity increased because of the adoption of IFRS. The paper further evidences that financial reporting quality in the post-IFRS period increased cost of equity. Finally, the paper finds that mature firms produce a better quality of earnings, which result in lower cost of capital. The results indicate that a mature firm was benefited because of the adoption of IFRS. Originality/value The finding of this research is useful to the regulators and practitioners to understand the widespread benefit of IFRS adoption.

scholarly journals Trypanosoma cruzi Phosphomannomutase and Guanosine Diphosphate-Mannose Pyrophosphorylase Ligandability Assessment

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Filip Zmuda ◽  
Sharon M. Shepherd ◽  
Michael A. J. Ferguson ◽  
David W. Gray ◽  
Leah S. Torrie ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Cell Surface ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
De Novo ◽  
Chemical Space ◽  
Nucleotide Sugar ◽  
Content Type ◽  
Life Cycle Stages ◽  
Drug Discovery Program

ABSTRACT Chagas’ disease, which is caused by the Trypanosoma cruzi parasite, has become a global health problem that is currently treated with poorly tolerated drugs that require prolonged dosing. Therefore, there is a clinical need for new therapeutic agents that can mitigate these issues. The phosphomannomutase (PMM) and GDP-mannose pyrophosphorylase (GDP-MP) enzymes form part of the de novo biosynthetic pathway to the nucleotide sugar GDP-mannose. This nucleotide sugar is used either directly, or indirectly via the formation of dolichol-phosphomannose, for the assembly of all mannose-containing glycoconjugates. In T. cruzi, mannose-containing glycoconjugates include the cell-surface glycoinositol-phospholipids and the glycosylphosphatidylinositol-anchored mucin-like glycoproteins that dominate the cell surface architectures of all life cycle stages. This makes PMM and GDP-MP potentially attractive targets for a drug discovery program against Chagas’ disease. To assess the ligandability of these enzymes in T. cruzi, we have screened 18,117 structurally diverse compounds exploring drug-like chemical space and 16,845 small polar fragment compounds using an assay interrogating the activities of both PMM and GDP-MP enzymes simultaneously. This resulted in 48 small fragment hits, and on retesting 20 were found to be active against the enzymes. Deconvolution revealed that these were all inhibitors of T. cruzi GDP-MP, with compounds 2 and 3 acting as uncompetitive and competitive inhibitors, respectively. Based on these findings, the T. cruzi PMM and GDP-MP enzymes were deemed not ligandable and poorly ligandable, respectively, using small molecules from conventional drug discovery chemical space. This presents a significant hurdle to exploiting these enzymes as therapeutic targets for Chagas’ disease.

scholarly journals Induction of Effective Immunity against Trypanosoma cruzi

2020 ◽  
Vol 88 (4) ◽  
Author(s):  
Tere Williams ◽  
Ignacio Guerrero-Ros ◽  
Yanfen Ma ◽  
Fabiane Matos dos Santos ◽  
Philipp E. Scherer ◽  
...  
Keyword(s):  
T Cells ◽  
Trypanosoma Cruzi ◽  
Immune Cells ◽  
Fluorescent Protein ◽  
Rapid Expansion ◽  
Public Health Issue ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Ifn Γ ◽  
Green Fluorescent

ABSTRACT Chagas disease, caused by Trypanosoma cruzi, is a major public health issue. Limitations in immune responses to natural T. cruzi infection usually result in parasite persistence with significant complications. A safe, effective, and reliable vaccine would reduce the threat of T. cruzi infections; however, no suitable vaccine is currently available due to a lack of understanding of the requirements for induction of fully protective immunity. We established a T. cruzi strain expressing green fluorescent protein (GFP) under the control of dihydrofolate reductase degradation domain (DDD) with a hemagglutinin (HA) tag, GFP-DDDHA, which was induced by trimethoprim-lactate (TMP-lactate), which results in the death of intracellular parasites. This attenuated strain induces very strong protection against reinfection. Using this GFP-DDDHA strain, we investigated the mechanisms underlying the protective immune response in mice. Immunization with this strain led to a response that included high levels of gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α), as well as a rapid expansion of effector and memory T cells in the spleen. More CD8+ T cells differentiate to memory cells following GFP-DDDHA infection than after infection with a wild-type (WT) strain. The GFP-DDDHA strain also provides cross-protection against another T. cruzi isolate. IFN-γ is important in mediating the protection, as IFN-γ knockout (KO) mice failed to acquire protection when infected with the GFP-DDDHA strain. Immune cells demonstrated earlier and stronger protective responses in immunized mice after reinfection with T. cruzi than those in naive mice. Adoptive transfers with several types of immune cells or with serum revealed that several branches of the immune system mediated protection. A combination of serum and natural killer cells provided the most effective protection against infection in these transfer experiments.

scholarly journals The steady-state transcriptome of the four major life-cycle stages of Trypanosoma cruzi

BMC Genomics ◽  
2009 ◽  
Vol 10 (1) ◽  
Author(s):  
Todd A Minning ◽  
D Brent Weatherly ◽  
James Atwood ◽  
Ron Orlando ◽  
Rick L Tarleton
Keyword(s):  
Life Cycle ◽  
Steady State ◽  
Trypanosoma Cruzi ◽  
Major Life ◽  
Life Cycle Stages

Is the performance improvement effect of social capital contingent on life cycle stages of professional athletes? Evidence from motorboat racing in Japan

2017 ◽  
Vol 44 (12) ◽  
pp. 2466-2485
Author(s):  
Nobuya Fukugawa
Keyword(s):  
Social Capital ◽  
Life Cycle ◽  
Fixed Effects ◽  
Negative Binomial ◽  
Professional Athletes ◽  
Physical Factors ◽  
Negative Binomial Regression Model ◽  
Content Type ◽  
Bridging Social Capital ◽  
Life Cycle Stages

Purpose The purpose of this paper is to examine whether bonding and bridging social capital of professional athletes affect their performance and whether the impacts vary according to their life cycle stages. Design/methodology/approach This study establishes an unbalanced panel of motorboat racers in Japan, and estimates a fixed-effects negative binomial regression model to analyze determining factors in the number of wins in a final, focusing on not only physical factors but also social capital. Findings Bridging social capital, measured by the number of racers in the same regional division, has no impact on performance. Bonding social capital, measured by the number of racers who graduated the training institute in the same period, has positive impacts on performance. This positive effect is more salient among racers who are less experienced, and thus need to extract benefits from social capital to augment limited internal resources. Originality/value This study adds statistical evidence to previous literature on the contingency theory that different types of social capital have different impacts on performance under different environments.

scholarly journals Governance and the corporate life-cycle

2015 ◽  
Vol 11 (1) ◽  
pp. 23-43 ◽  
Author(s):  
Thomas O'Connor ◽  
Julie Byrne
Keyword(s):  
Corporate Governance ◽  
Life Cycle ◽  
Prediction Model ◽  
Design Methodology ◽  
Emerging Market ◽  
Content Type ◽  
Emerging Market Countries ◽  
Life Cycle Stages ◽  
Corporate Life Cycle ◽  
Resource Strategy

Purpose – The purpose of this paper is to examine whether corporate governance changes along the corporate life-cycle. Design/methodology/approach – In a sample of 205 firms from 21 emerging market countries and using a life-cycle proxy from the dividends literature, the authors use a governance-prediction model which examines whether corporate governance differs along the corporate life-cycle. Findings – Mature firms tend to practice better overall corporate governance. Discipline and independence improve as firms mature. Firms tend to be most transparent and accountable when they are young. These findings suggest that the resource/strategy and monitoring/control governance functions are relevant but at different life-cycle stages. Research limitations/implications – In the absence of longitudinal governance data with sufficient coverage to track within-firm changes in corporate governance along the corporate life-cycle, the authors analyze differences in corporate governance between-firms at different life-cycle stages. Originality/value – The authors use an alternative, yet new measure from the dividends literature to account for the firm’s position along the corporate life-cycle. With this new measure, the findings are in line with the predictions of Filatotchev et al. (2006).

scholarly journals The Life Cycle Stages of Pneumocystis murina Have Opposing Effects on the Immune Response to This Opportunistic Fungal Pathogen

2016 ◽  
Vol 84 (11) ◽  
pp. 3195-3205 ◽  
Author(s):  
Heather M. Evans ◽  
Grady L. Bryant ◽  
Beth A. Garvy
Keyword(s):  
Cell Wall ◽  
Life Cycle ◽  
Immune Responses ◽  
Immune Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Content Type ◽  
Life Cycle Stages ◽  
Ifn Γ

The cell wall β-glucans of Pneumocystis cysts have been shown to stimulate immune responses in lung epithelial cells, dendritic cells, and alveolar macrophages. Little is known about how the trophic life forms, which do not have a fungal cell wall, interact with these innate immune cells. Here we report differences in the responses of both neonatal and adult mice to the trophic and cystic life cycle stages of Pneumocystis murina . The adult and neonatal immune responses to infection with Pneumocystis murina trophic forms were less robust than the responses to infection with a physiologically normal mixture of cysts and trophic forms. Cysts promoted the recruitment of nonresident innate immune cells and T and B cells into the lungs. Cysts, but not trophic forms, stimulated increased concentrations of the cytokine gamma interferon (IFN-γ) in the alveolar spaces and an increase in the percentage of CD4 + T cells that produce IFN-γ. In vitro , bone marrow-derived dendritic cells (BMDCs) stimulated with cysts produced the proinflammatory cytokines interleukin 1β (IL-1β) and IL-6. In contrast, trophic forms suppressed antigen presentation to CD4 + T cells, as well as the β-glucan-, lipoteichoic acid (LTA)-, and lipopolysaccharide (LPS)-induced production of interleukin 1β (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α) by BMDCs. The negative effects of trophic forms were not due to ligation of mannose receptor. Our results indicate that optimal innate and adaptive immune responses to Pneumocystis species are dependent on stimulation with the cyst life cycle stage. Conversely, trophic forms suppress β-glucan-induced proinflammatory responses in vitro , suggesting that the trophic forms dampen cyst-induced inflammation in vivo .

The dividend signaling hypothesis and the corporate life cycle

2020 ◽  
Vol 46 (12) ◽  
pp. 1569-1587
Author(s):  
Narcisa Meza ◽  
Anibal Báez ◽  
Javier Rodriguez ◽  
Wilfredo Toledo
Keyword(s):  
Life Cycle ◽  
Growth Stages ◽  
Content Type ◽  
Future Earnings ◽  
Life Cycle Stages ◽  
Dividend Signaling ◽  
Corporate Life Cycle ◽  
Firm’S Life Cycle ◽  
Signaling Hypothesis ◽  
The Relationship

PurposeThis paper aims to examine the relationship between the dividend signaling hypothesis and a firm's life cycle.Design/methodology/approachThe authors use Dickinson's (2011) methodology to develop a proxy for the firm's stages in its life cycle and to examine the relationship between dividends and future earnings following a nonlinear setting.FindingsUsing a sample of US firms during the 2000–2014 period, the authors find that the signaling hypothesis can be dependent on firm-specific characteristics, such as life cycle stages. The authors report that the relationship between dividend changes and subsequent earnings changes is different for different life stages. They also find that changes in the amount of the dividend provide some information about future earnings, especially during the early (introductory and growth) stages. These results are consistent with the use of earnings or return on assets as the dependent variables in models of earnings expectations.Originality/valueThe authors believe that this is the first time that the dividend signaling hypothesis has been linked to the life cycle of the firm.

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