scholarly journals The Tlo Proteins Are Stoichiometric Components of Candida albicans Mediator Anchored via the Med3 Subunit

2012 ◽  
Vol 11 (7) ◽  
pp. 874-884 ◽  
Author(s):  
Anda Zhang ◽  
Kostadin O. Petrov ◽  
Emily R. Hyun ◽  
Zhongle Liu ◽  
Scott A. Gerber ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Potential Role ◽  
Close Relative ◽  
Physical Interaction ◽  
Mechanistic Studies ◽  
Content Type ◽  
Gene Regulatory ◽  
Germ Tubes ◽  
Coactivator Complex

ABSTRACTThe amplification of theTLO(fortelomere-associated) genes inCandida albicans, compared to its less pathogenic, close relativeCandida dubliniensis, suggests a role in virulence. Little, however, is known about the function of the Tlo proteins. We have purified the Mediator coactivator complex fromC. albicans(caMediator) and found that Tlo proteins are a stoichiometric component of caMediator. Many members of the Tlo family are expressed, and each is a unique member of caMediator. Protein expression analysis of individual Tlo proteins, as well as the purification of tagged Tlo proteins, demonstrate that there is a large free population of Tlo proteins in addition to the Mediator-associated population. Coexpression and copurification of Tloα12 and caMed3 inEscherichia coliestablished a direct physical interaction between the two proteins. We have also made aC. albicansmed3Δ/Δstrain and purified an intact Mediator from this strain. The analysis of the composition of themed3ΔMediator shows that it lacks a Tlo subunit. Regarding Mediator function, themed3Δ/Δstrain serves as a substitute for the difficult-to-maketloΔ/Δ C. albicansstrain. A potential role of theTLOandMED3genes in virulence is supported by the inability of themed3Δ/Δstrain to form normal germ tubes. This study of caMediator structure provides initial clues to the mechanism of action of the Tlo genes and a platform for further mechanistic studies of caMediator's involvement in gene regulatory patterns that underlie pathogenesis.

Revitalising Waqf (endowment) lands for agribusiness: potentials of the anchor company models

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Norfaridah Ali Azizan ◽  
Amirul Afif Muhamat ◽  
Sharifah Faigah Syed Alwi ◽  
Husniyati Ali ◽  
Amalia Qistina Casteneda Abdullah
Keyword(s):  
Household Income ◽  
Design Methodology ◽  
Potential Role ◽  
Islamic Law ◽  
Living Condition ◽  
Previous Literature ◽  
Content Type ◽  
Muslim Countries ◽  
The Right

PurposeWaqf (endowment) lands constitute as among the highest types of waqf (endowment) properties in Malaysia; yet it is still unable to reach its maximum potential due to various challenges such as capital, location, legal and administrative issues. Therefore, this study intends to explore these issues by focussing on the two states in Malaysia (Selangor and Perak) that have fertile lands but different management authorities.Design/methodology/approachThere were series of interviews that had been conducted with ten (10) key informants who are experts and practitioners in the areas of Shariah (Islamic law), farming, agribusiness, land management and waqf.FindingsFindings exhibit that constraints and challenges that had been highlighted in the previous literature still exist (although some improvements had been made), but there is emerging theme that the study intends to highlight which is on the needs to secure market for the agribusiness produce and the potential role of anchor company in the agribusiness. It is pertinent that for agribusiness to thrive, selecting the right anchor company that has the capacity to address the challenges is necessary. This study posits two anchor company models (Waqf Trustee-Anchor Company and Waqf Trustee-Anchor Company-Community Farmers) that can be applied for agribusiness on the waqf lands.Research limitations/implicationsThis study is based on the Malaysia's context influenced by specific country's features. Nevertheless, such findings can still be used as reference or benchmark by other endowment trustees in other countries especially for the Muslim countries as well as the non-Muslim countries that have significant Muslim populations.Social implicationsThe suggested models have potentials to improve the living condition of the B40 (below 40% household income) in Malaysia because the models encourage their participation in the agribusiness activities.Originality/valueThis study focusses on the agribusiness, which is rarely being given attention in previous literature in the context of endowment lands. Therefore, this article bridges the literature gap and at the same time attempts to provide suggestion to address the pertinent issue – the underutilised endowment lands.

scholarly journals Role of Matrix β-1,3 Glucan in Antifungal Resistance of Non-albicans Candida Biofilms

2013 ◽  
Vol 57 (4) ◽  
pp. 1918-1920 ◽  
Author(s):  
K. F. Mitchell ◽  
H. T. Taff ◽  
M. A. Cuevas ◽  
E. L. Reinicke ◽  
H. Sanchez ◽  
...  
Keyword(s):  
Health Care ◽  
Drug Resistance ◽  
Candida Albicans ◽  
Care Setting ◽  
Antifungal Susceptibility ◽  
Antifungal Drug ◽  
Content Type ◽  
The Matrix ◽  
Biofilm Matrix

ABSTRACTCandidabiofilm infections pose an increasing threat in the health care setting due to the drug resistance associated with this lifestyle. Several mechanisms underlie the resistance phenomenon. InCandida albicans, one mechanism involves drug impedance by the biofilm matrix linked to β-1,3 glucan. Here, we show this is important for otherCandidaspp. We identified β-1,3 glucan in the matrix, found that the matrix sequesters antifungal drug, and enhanced antifungal susceptibility with matrix β-1,3 glucan hydrolysis.

scholarly journals Nucleotide Excision Repair Protein Rad23 Regulates Cell Virulence Independent of Rad4 in Candida albicans

mSphere ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Jia Feng ◽  
Shuangyan Yao ◽  
Yansong Dong ◽  
Jing Hu ◽  
Malcolm Whiteway ◽  
...  
Keyword(s):  
Dna Damage ◽  
Candida Albicans ◽  
Nucleotide Excision Repair ◽  
Dna Damage Response ◽  
Excision Repair ◽  
Content Type ◽  
Virulence Regulation ◽  
Nucleotide Excision ◽  
Damage Response

ABSTRACT In the pathogenic yeast Candida albicans, the DNA damage response contributes to pathogenicity by regulating cell morphology transitions and maintaining survival in response to DNA damage induced by reactive oxygen species (ROS) in host cells. However, the function of nucleotide excision repair (NER) in C. albicans has not been extensively investigated. To better understand the DNA damage response and its role in virulence, we studied the function of the Rad23 nucleotide excision repair protein in detail. The RAD23 deletion strain and overexpression strain both exhibit UV sensitivity, confirming the critical role of RAD23 in the nucleotide excision repair pathway. Genetic interaction assays revealed that the role of RAD23 in the UV response relies on RAD4 but is independent of RAD53, MMS22, and RAD18. RAD4 and RAD23 have similar roles in regulating cell morphogenesis and biofilm formation; however, only RAD23, but not RAD4, plays a negative role in virulence regulation in a mouse model. We found that the RAD23 deletion strain showed decreased survival in a Candida-macrophage interaction assay. Transcriptome sequencing (RNA-seq) and quantitative real-time PCR (qRT-PCR) data further revealed that RAD23, but not RAD4, regulates the transcription of a virulence factor, SUN41, suggesting a unique role of RAD23 in virulence regulation. Taking these observations together, our work reveals that the RAD23-related nucleotide excision pathway plays a critical role in the UV response but may not play a direct role in virulence. The virulence-related role of RAD23 may rely on the regulation of several virulence factors, which may give us further understanding about the linkage between DNA damage repair and virulence regulation in C. albicans. IMPORTANCE Candida albicans remains a significant threat to the lives of immunocompromised people. An understanding of the virulence and infection ability of C. albicans cells in the mammalian host may help with clinical treatment and drug discovery. The DNA damage response pathway is closely related to morphology regulation and virulence, as well as the ability to survive in host cells. In this study, we checked the role of the nucleotide excision repair (NER) pathway, the key repair system that functions to remove a large variety of DNA lesions such as those caused by UV light, but whose function has not been well studied in C. albicans. We found that Rad23, but not Rad4, plays a role in virulence that appears independent of the function of the NER pathway. Our research revealed that the NER pathway represented by Rad4/Rad23 may not play a direct role in virulence but that Rad23 may play a unique role in regulating the transcription of virulence genes that may contribute to the virulence of C. albicans.

scholarly journals Exosomic microRNAs as emerging key regulators of intercellular communication in the tumor microenvironment and beyond

2016 ◽  
Vol 2 (1) ◽  
Author(s):  
Mariam Murtadha ◽  
Muller Fabbri
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Patients ◽  
Intercellular Communication ◽  
Potential Role ◽  
Biological Fluids ◽  
Healthy Controls ◽  
Gene Regulatory ◽  
Non Coding Rnas ◽  
Regulatory Functions

AbstractMicroRNAs (miRs) are small non-coding RNAs with key gene regulatory functions. Recent evidence has shown that miRs have a central role in shaping the biology of the Tumor Microenvironment (TME). The discovery that some exosomes contain high levels of miR cargo that shuttle between cells and mediate intercellular cross-talk has shifted the focus of miR research towards understanding the biological role of exosomic miRs. In this review, we highlight the emerging role of exosomic miRs in molding the tumor microenvironment towards pro-tumor conditions by altering intercellular communication. We briefly discuss some mechanisms of selective loading of miRs into exosomes, as well as emerging evidence that exosomic miRs are present in all biological fluids. Furthermore, we describe the differences in the exosomic miR signatures between cancer patients and healthy controls, and the potential role of exosomic miRs as diagnostic, prognostic, and therapeutic biomarkers.

Marketing to the “middle of the pyramid” in emerging markets using a social network perspective

2014 ◽  
Vol 9 (3) ◽  
pp. 400-423 ◽  
Author(s):  
Tendai Chikweche ◽  
Richard Fletcher
Keyword(s):  
Social Networks ◽  
Middle Class ◽  
Potential Role ◽  
Content Type ◽  
Business Executives ◽  
Advanced Economies ◽  
Sub Saharan ◽  
Corporate Social ◽  
The Impact

Purpose – The purpose of this paper is to expand knowledge about how middle class consumers in Sub-Saharan African markets behave, focusing on the potential role of social networks and the subsequent interactions that take place between these consumers and firms. Design/methodology/approach – A qualitative research method approach comprising personal interviews and observations targeted at consumers and business executives was used covering all four countries. Findings – Key findings include identification of middle of the pyramid (MOP) social networks, their impact on consumer behaviour and nature of consumer and firm interactions that take place as a result of the impact of social networks. Research limitations/implications – The sample size was restricted to 80 consumers in each of the four countries. This might limit generalisability. Practical implications – The study provides managers with insights on the potential role of social networks on marketing to the MOP in Africa. Social implications – The study provides managers with insights on the potential opportunities for corporate social responsibility solutions at the MOP. Originality/value – Research into the middle class in markets other than western advanced economies is a relatively new area of study. The majority of studies on the middle class have focused on North America and Europe ignoring the merging middle class in Africa. Hence, this research expands knowledge by providing basis for exploring new insights on the emerging marketing opportunity within the middle class in Africa.

scholarly journals Propranolol Inhibits Hyphal Development in Candida albicans

2002 ◽  
Vol 46 (11) ◽  
pp. 3617-3620 ◽  
Author(s):  
Carol A. Baker ◽  
Kevin Desrosiers ◽  
Joseph W. Dolan
Keyword(s):  
Growth Rate ◽  
Candida Albicans ◽  
Phosphatidic Acid ◽  
Rate Data ◽  
Dimorphic Transition ◽  
Hyphal Development ◽  
Germ Tubes ◽  
Hydrolysis Of

ABSTRACT Propranolol was used to investigate the role of phosphatidic acid (PA) and diacylglycerol in the dimorphic transition in Candida albicans. Propranolol was able to inhibit the appearance of germ tubes without decreasing growth rate. Data suggest that inhibition of morphogenesis may be due to binding by propranolol of PA derived from PLD1 hydrolysis of phosphatidylcholine.

The relationship between cooperative and competitive behavioral tendencies and trust in coworkers

2020 ◽  
Vol 8 (3) ◽  
pp. 345-360
Author(s):  
Ece Ömüriş ◽  
Ferda Erdem ◽  
Janset Özen Aytemur
Keyword(s):  
Mixed Methods Research ◽  
Potential Role ◽  
Employee Relations ◽  
Hierarchical Regression ◽  
Future Research ◽  
Content Type ◽  
Tourism Sector ◽  
Behavioral Tendencies ◽  
The Relationship

PurposeThis study aims to investigate the relationship between cooperative and competitive behavioral tendencies and trust of coworkers in organizations. Two main hypotheses were developed. The first hypothesis was that cooperativeness and trust in coworkers is positively correlated. The second hypothesis was that competitiveness and trust in coworkers is negatively correlated.Design/methodology/approachThe sample was 442 Turkish tourism sector employees in a labor-intensive industry. Two scales were used to measure trust in coworkers and cooperativeness/competitiveness. A hierarchical regression analysis was performed to understand how individuals' behavioral tendency affects their coworkers' trust in them.FindingsThe findings strongly supported the first hypothesis, in that cooperativeness was positively correlated with trust in coworkers. The second hypothesis was only partially supported because there was no significant relationship between competitiveness and the competency and trustworthiness dimensions of trust. Unselfishness aspect of trust, however, was negatively correlated with competitiveness.Research limitations/implicationsThe main contribution of this study is to show that employee cooperativeness and competitiveness can affect trust in coworker relations. However, the measurement of competitiveness and cooperativeness measurement had limitations due to differences in the culture-specific meanings of cooperation and competition. Future research employing mixed methods research is needed to further explain the content of the two tendencies and the relationship between the concepts.Originality/valueThe literature on trust and employee relations tends to focus more on the issue of trust between managers and subordinates while neglecting the complex and multifaceted structure of trust in employee–employer relations. However, new working forms mean that horizontal relations are increasingly important. Therefore, more research is needed to address the tendencies and structures that affect trust in coworkers. This study draws attention to the potential role of cooperative and competitive behaviors in trust in horizontal employee relations.

scholarly journals Differential Regulation of White-Opaque Switching by Individual Subunits of Candida albicans Mediator

2013 ◽  
Vol 12 (9) ◽  
pp. 1293-1304 ◽  
Author(s):  
Anda Zhang ◽  
Zhongle Liu ◽  
Lawrence C. Myers
Keyword(s):  
Candida Albicans ◽  
Ectopic Expression ◽  
Small Subset ◽  
Content Type ◽  
Impaired Ability ◽  
Transcriptional Effect ◽  
Environmental Induction ◽  
Gene Regulatory ◽  
The Stability ◽  
Negative Gene

ABSTRACT The multisubunit eukaryotic Mediator complex integrates diverse positive and negative gene regulatory signals and transmits them to the core transcription machinery. Mutations in individual subunits within the complex can lead to decreased or increased transcription of certain subsets of genes, which are highly specific to the mutated subunit. Recent studies suggest a role for Mediator in epigenetic silencing. Using white-opaque morphological switching in Candida albicans as a model, we have shown that Mediator is required for the stability of both the epigenetic silenced (white) and active (opaque) states of the bistable transcription circuit driven by the master regulator Wor1. Individual deletions of eight C. albicans Mediator subunits have shown that different Mediator subunits have dramatically diverse effects on the directionality, frequency, and environmental induction of epigenetic switching. Among the Mediator deletion mutants analyzed, only Med12 has a steady-state transcriptional effect on the components of the Wor1 circuit that clearly corresponds to its effect on switching. The MED16 and MED9 genes have been found to be among a small subset of genes that are required for the stability of both the white and opaque states. Deletion of the Med3 subunit completely destabilizes the opaque state, even though the Wor1 transcription circuit is intact and can be driven by ectopic expression of Wor1. The highly impaired ability of the med3 deletion mutant to mate, even when Wor1 expression is ectopically induced, reveals that the activation of the Wor1 circuit can be decoupled from the opaque state and one of its primary biological consequences.

scholarly journals Aspergillus fumigatus Intrinsic Fluconazole Resistance Is Due to the Naturally Occurring T301I Substitution in Cyp51Ap

2016 ◽  
Vol 60 (9) ◽  
pp. 5420-5426 ◽  
Author(s):  
Florencia Leonardelli ◽  
Daiana Macedo ◽  
Catiana Dudiuk ◽  
Matias S. Cabeza ◽  
Soledad Gamarra ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Aspergillus Fumigatus ◽  
Parental Strain ◽  
Amino Acid Residues ◽  
Intrinsic Resistance ◽  
Single Nucleotide ◽  
Fluconazole Resistance ◽  
Content Type ◽  
Natural Polymorphism

ABSTRACTAspergillus fumigatusintrinsic fluconazole resistance has been demonstrated to be linked to theCYP51Agene, although the precise molecular mechanism has not been elucidated yet. Comparisons betweenA. fumigatusCyp51Ap andCandida albicansErg11p sequences showed differences in amino acid residues already associated with fluconazole resistance inC. albicans. The aim of this study was to analyze the role of the natural polymorphism I301 inAspergillus fumigatusCyp51Ap in the intrinsic fluconazole resistance phenotype of this pathogen. The I301 residue inA. fumigatusCyp51Ap was replaced with a threonine (analogue to T315 atCandida albicansfluconazole-susceptible Erg11p) by changing one single nucleotide in theCYP51Agene. Also, aCYP51Aknockout strain was obtained using the same parental strain. Both mutants' antifungal susceptibilities were tested. The I301T mutant exhibited a lower level of resistance to fluconazole (MIC, 20 μg/ml) than the parental strain (MIC, 640 μg/ml), while no changes in MIC were observed for other azole- and non-azole-based drugs. These data strongly implicate theA. fumigatusCyp51Ap I301 residue in the intrinsic resistance to fluconazole.

scholarly journals Regulation of Pathogenic Spore Germination by CgRac1 in the Fungal Plant Pathogen Colletotrichum gloeosporioides

2011 ◽  
Vol 10 (8) ◽  
pp. 1122-1130 ◽  
Author(s):  
Iris Nesher ◽  
Anna Minz ◽  
Leonie Kokkelink ◽  
Paul Tudzynski ◽  
Amir Sharon
Keyword(s):  
Cell Division ◽  
Plant Pathogen ◽  
Germ Tube ◽  
Colletotrichum Gloeosporioides ◽  
Fluorescent Protein ◽  
Nuclear Division ◽  
Simultaneous Formation ◽  
Content Type ◽  
Germ Tubes

ABSTRACT Colletotrichum gloeosporioides is a facultative plant pathogen: it can live as a saprophyte on dead organic matter or as a pathogen on a host plant. Different patterns of conidial germination have been recognized under saprophytic and pathogenic conditions, which also determine later development. Here we describe the role of CgRac1 in regulating pathogenic germination. The hallmark of pathogenic germination is unilateral formation of a single germ tube following the first cell division. However, transgenic strains expressing a constitutively active CgRac1 (CA-CgRac1) displayed simultaneous formation of two germ tubes, with nuclei continuing to divide in both cells after the first cell division. CA-CgRac1 also caused various other abnormalities, including difficulties in establishing and maintaining cell polarity, reduced conidial and hyphal adhesion, and formation of immature appressoria. Consequently, CA-CgRac1 isolates were completely nonpathogenic. Localization studies with cyan fluorescent protein (CFP)-CgRac1 fusion protein showed that the CgRac1 protein is abundant in conidia and in hyphal tips. Although the CFP signal was equally distributed in both cells of a germinating conidium, reactive oxygen species accumulated only in the cell that produced a germ tube, indicating that CgRac1 was active only in the germinating cell. Collectively, our results show that CgRac1 is a major regulator of asymmetric development and that it is involved in the regulation of both morphogenesis and nuclear division. Modification of CgRac1 activity disrupts the morphogenetic program and prevents fungal infection.

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