scholarly journals Plasmodium Helical Interspersed Subtelomeric (PHIST) Proteins, at the Center of Host Cell Remodeling

2016 ◽  
Vol 80 (4) ◽  
pp. 905-927 ◽  
Author(s):  
Jan D. Warncke ◽  
Ioannis Vakonakis ◽  
Hans-Peter Beck

SUMMARYDuring the asexual cycle,Plasmodium falciparumextensively remodels the human erythrocyte to make it a suitable host cell. A large number of exported proteins facilitate this remodeling process, which causes erythrocytes to become more rigid, cytoadherent, and permeable for nutrients and metabolic products. Among the exported proteins, a family of 89 proteins, called thePlasmodiumhelical interspersed subtelomeric (PHIST) protein family, has been identified. While also found in otherPlasmodiumspecies, the PHIST family is greatly expanded inP. falciparum. Although a decade has passed since their first description, to date, most PHIST proteins remain uncharacterized and are of unknown function and localization within the host cell, and there are few data on their interactions with other host or parasite proteins. However, over the past few years, PHIST proteins have been mentioned in the literature at an increasing rate owing to their presence at various localizations within the infected erythrocyte. Expression of PHIST proteins has been implicated in molecular and cellular processes such as the surface display of PfEMP1, gametocytogenesis, changes in cell rigidity, and also cerebral and pregnancy-associated malaria. Thus, we conclude that PHIST proteins are central to host cell remodeling, but despite their obvious importance in pathology, PHIST proteins seem to be understudied. Here we review current knowledge, shed light on the definition of PHIST proteins, and discuss these proteins with respect to their localization and probable function. We take into consideration interaction studies, microarray analyses, or data from blood samples from naturally infected patients to combine all available information on this protein family.

2014 ◽  
Vol 13 (8) ◽  
pp. 965-976 ◽  
Author(s):  
Ira J. Blader ◽  
Anita A. Koshy

ABSTRACTIntracellular pathogens can replicate efficiently only after they manipulate and modify their host cells to create an environment conducive to replication. While diverse cellular pathways are targeted by different pathogens, metabolism, membrane and cytoskeletal architecture formation, and cell death are the three primary cellular processes that are modified by infections.Toxoplasma gondiiis an obligate intracellular protozoan that infects ∼30% of the world's population and causes severe and life-threatening disease in developing fetuses, in immune-comprised patients, and in certain otherwise healthy individuals who are primarily found in South America. The high prevalence ofToxoplasmain humans is in large part a result of its ability to modulate these three host cell processes. Here, we highlight recent work defining the mechanisms by whichToxoplasmainteracts with these processes. In addition, we hypothesize why some processes are modified not only in the infected host cell but also in neighboring uninfected cells.


2019 ◽  
Vol 88 (3) ◽  
Author(s):  
Bhavna Padmanabhan ◽  
Laura F. Fielden ◽  
Abderrahman Hachani ◽  
Patrice Newton ◽  
David R. Thomas ◽  
...  

ABSTRACT Coxiella burnetii is an obligate intracellular bacterial pathogen that replicates inside the lysosome-derived Coxiella-containing vacuole (CCV). To establish this unique niche, C. burnetii requires the Dot/Icm type IV secretion system (T4SS) to translocate a cohort of effector proteins into the host cell, which modulate multiple cellular processes. To characterize the host-pathogen interactions that occur during C. burnetii infection, stable-isotope labeling by amino acids in cell culture (SILAC)-based proteomics was used to identify changes in the host proteome during infection of a human-derived macrophage cell line. These data revealed that the abundances of many proteins involved in host cell autophagy and lysosome biogenesis were increased in infected cells. Thus, the role of the host transcription factors TFEB and TFE3, which regulate the expression of a network of genes involved in autophagy and lysosomal biogenesis, were examined in the context of C. burnetii infection. During infection with C. burnetii, both TFEB and TFE3 were activated, as demonstrated by the transport of these proteins from the cytoplasm into the nucleus. The nuclear translocation of these transcription factors was shown to be dependent on the T4SS, as a Dot/Icm mutant showed reduced nuclear translocation of TFEB and TFE3. This was supported by the observation that blocking bacterial translation with chloramphenicol resulted in the movement of TFEB and TFE3 back into the cytoplasm. Silencing of the TFEB and TFE3 genes, alone or in combination, significantly reduced the size of the CCV, which indicates that these host transcription factors facilitate the expansion and maintenance of the organelle that supports C. burnetii intracellular replication.


2015 ◽  
Vol 198 (1) ◽  
pp. 47-54 ◽  
Author(s):  
Natalia Tschowri

The cyclic dinucleotides cyclic 3′,5′-diguanylate (c-di-GMP) and cyclic 3′,5′-diadenylate (c-di-AMP) have emerged as key components of bacterial signal transduction networks. These closely related second messengers follow the classical general principles of nucleotide signaling by integrating diverse signals into regulatory pathways that control cellular responses to changing environments. They impact distinct cellular processes, with c-di-GMP having an established role in promoting bacterial adhesion and inhibiting motility and c-di-AMP being involved in cell wall metabolism, potassium homeostasis, and DNA repair. The involvement of c-dinucleotides in the physiology of the filamentous, nonmotile streptomycetes remained obscure until recent discoveries showed that c-di-GMP controls the activity of the developmental master regulator BldD and that c-di-AMP determines the level of the resuscitation-promoting factor A(RpfA) cell wall-remodelling enzyme. Here, I summarize our current knowledge of c-dinucleotide signaling inStreptomycesspecies and highlight the important roles of c-di-GMP and c-di-AMP in the biology of these antibiotic-producing, multicellular bacteria.


2015 ◽  
Vol 61 (9) ◽  
pp. 617-635 ◽  
Author(s):  
Ernest C. So ◽  
Corinna Mattheis ◽  
Edward W. Tate ◽  
Gad Frankel ◽  
Gunnar N. Schroeder

The Gram-negative facultative intracellular pathogen Legionella pneumophila infects a wide range of different protozoa in the environment and also human alveolar macrophages upon inhalation of contaminated aerosols. Inside its hosts, it creates a defined and unique compartment, termed the Legionella-containing vacuole (LCV), for survival and replication. To establish the LCV, L. pneumophila uses its Dot/Icm type IV secretion system (T4SS) to translocate more than 300 effector proteins into the host cell. Although it has become apparent in the past years that these effectors subvert a multitude of cellular processes and allow Legionella to take control of host cell vesicle trafficking, transcription, and translation, the exact function of the vast majority of effectors still remains unknown. This is partly due to high functional redundancy among the effectors, which renders conventional genetic approaches to elucidate their role ineffective. Here, we review the current knowledge about Legionella T4SS effectors, highlight open questions, and discuss new methods that promise to facilitate the characterization of T4SS effector functions in the future.


2018 ◽  
Vol 10 (2) ◽  
pp. 361-383 ◽  
Author(s):  
Shaza Aldairany ◽  
Rosmini Omar ◽  
Farzana Quoquab

Purpose Conflict environments are under researchers’ scope in many disciplines at micro and macro levels. This paper aims to steer towards finding out how literature addresses entrepreneurship in conflict contexts. In addition, this paper tries to ascertain the theoretical bases and main themes and issues that have been studied in this area, to map the current knowledge in a clear frame as an attempt to highlight gaps and weaknesses in relevant literature. Design/methodology/approach Review entrepreneurship, conflict and post-conflict literature including the terminologies, theories, methodologies are the main themes. The primary sources of data are research articles that were published in scholarly journals and written in English. The paper includes, in the final list of reviewed articles, 57 articles. Findings The review reveals three main themes of the special definition of entrepreneurship in conflict areas. Many gaps remain, despite the growing interests. More involvement in collecting data directly from the area under conflict is required instead of the heavy dependency on secondary data. In addition, destructive business and conflict consequences have promising research issues to be discovered more in single places or collectively for broader comprehensiveness. These findings may assist researchers, policymakers and international bodies to approach the current literature and build farther on it. Originality/value This paper attempts to provide a mapping of literature that focuses on how entrepreneurship in conflict and post-conflict could differ or be similar to stable contexts. The findings advance motivation for future empirical studies to encompass issues and development of entrepreneurship orientation, taxonomies and impacts in conflict and post-conflict contexts.


Author(s):  
Jan D. Warncke ◽  
Hans-Peter Beck

SUMMARYThe asexual intraerythrocytic development ofPlasmodium falciparum, causing the most severe form of human malaria, is marked by extensive host cell remodeling. Throughout the processes of invasion, intracellular development, and egress, the erythrocyte membrane skeleton is remodeled by the parasite as required for each specific developmental stage. The remodeling is facilitated by a plethora of exported parasite proteins, and the erythrocyte membrane skeleton is the interface of most of the observed interactions between the parasite and host cell proteins. Host cell remodeling has been extensively described and there is a vast body of information on protein export or the description of parasite-induced structures such as Maurer’s clefts or knobs on the host cell surface. Here we specifically review the molecular level of each host cell-remodeling step at each stage of the intraerythrocytic development ofP. falciparum. We describe key events, such as invasion, knob formation, and egress, and identify the interactions between exported parasite proteins and the host cell cytoskeleton. We discuss each remodeling step with respect to time and specific requirement of the developing parasite to explain host cell remodeling in a stage-specific manner. Thus, we highlight the interaction with the host membrane skeleton as a key event in parasite survival.


2020 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Luís Sanhudo ◽  
João Poças Martins ◽  
Nuno M.M. Ramos ◽  
Ricardo M.S.F. Almeida ◽  
Ana Rocha ◽  
...  

PurposeThis paper aims to further the discussion on Building Information Modelling (BIM) legal requirements, providing a framework with key energy parameters capable of supporting the Appointing Party in the definition of the Exchange Information Requirements (EIR) for a BIM project appointment. The EIR is described in ISO-19650–1:2018 as a fundamental step in the information delivery cycle.Design/methodology/approachA literature review on the topic of BIM energy analysis was completed to identify current knowledge gaps and support the need for the proposed framework. Afterwards, the framework was established based on the review findings and the authors’ domain knowledge. The applicability of the proposed framework was assessed through a case study, where several energy simulations were performed in three different design stages of the same BIM model.FindingsThis study identified a lack of standards and legislation capable of supporting the Appointing Party in the definition of energy-related BIM requirements. To this end, a new framework is proposed to mediate existing practices, linking prior knowledge with BIM’s new reality. The study showcases the applicability of the framework, identifying that the performance of different energy studies involves distinct Level of Development (LOD) requirements, which in turn have an impact on the modelling time and cost.Originality/valueA BIM framework for the specification of information requirements in energy-related projects was developed to support the Appointing Party. The framework presents appropriate parameters for energy analysis in each design stage, as well as the suitable LOD for the BIM model.


2020 ◽  
Vol 54 (1) ◽  
pp. qjegh2020-031 ◽  
Author(s):  
L. Battaglini ◽  
S. D′Angelo ◽  
A. Fiorentino

EMODnet Geology Project work package 6 collects information regarding ‘Geological events and probabilities’, including submarine landslides, earthquakes, volcanic centres, tsunamis, fluid emissions and tectonics. The elaboration of guidelines to compile GIS layers was aimed at identifying parameters to be used to thoroughly characterize each event. Particular attention has been devoted to the definition of the ‘Attribute tables’ in order to achieve the best degree of harmonization and standardization complying with the European INSPIRE Directive. Due to the different geological settings of European seas it was necessary to elaborate a comprehensive and detailed pattern of attributes for the different features, in order to represent each occurrence at different scales. The huge amount of data received has been processed, validated and standardized, thus obtaining homogeneous data layers at a European level. Metadata and available information collated during the project are displayed on the EMODnet Geology Portal (http://www.emodnet-geology.eu/). By combining all these data it may be possible to elaborate additional thematic maps which could support further research as well as land planning and management. The Geological Survey of Italy is testing one of these potential applications, which addresses the production of a structural model for submerged areas in Italy.Thematic collection: This article is part of the Mapping the Geology and Topography of the European Seas (EMODnet) collection available at: https://www.lyellcollection.org/cc/EMODnet


2021 ◽  
Author(s):  
Alexandra Blancke Soares ◽  
Jan Stäcker ◽  
Svenja Schwald ◽  
Wieteke Hoijmakers ◽  
Nahla Galal Metwally ◽  
...  

AbstractIntracellular malaria blood stage parasites remodel their host cell, a process essential for parasite survival and a cause of pathology in malaria infections. Host cell remodeling depends on the export of different classes of exported parasite proteins into the infected red blood cell (RBC). Here we show that members of a recently discovered group of difficult to predict exported proteins harbor an N-terminal export domain, similar to other classes of exported proteins, indicating that this is a common theme among all classes of exported proteins. For one such protein, MSRP6 (MSP-7 related protein 6), we identified a second, untypical export-mediating domain that corresponded to its MSP7-like region. In addition to its function in export, this domain also mediated attachment to the Maurer’s clefts, prominent parasite-induced structures in the host cell where MSRP6 is located. Using BioID with the Maurer’s clefts attachment domain of MSRP6 to identify interactors and compartment neighbors in live parasites we discovered a novel complex of proteins at the Maurer’s clefts. We show that this complex is necessary for the anchoring and maintaining the structural integrity of the Maurer’s clefts. The Maurer’s clefts are believed to be involved in the transport of the major virulence factor PfEMP1 to the host cell surface where it mediates cytoadherence of infected RBCs to endothelial cells, a main reason for the importance of host cell modifications for parasite virulence in the human host. Taking advantage of MSRP6 complex mutants and IT4 parasites that we modified to express only one specific PfEMP1 we find that abolishing Maurer’s clefts anchoring was neither needed for PfEMP1 transport to the host cell surface nor for cytoadherence. Altogether, this work reveals parasite proteins involved in Maurer’s clefts anchoring and maintenance and unexpectedly finds that these functions are dispensable for virulence factor transport and surface display.


Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1460
Author(s):  
Rebecca M. Boys ◽  
Ngaio J. Beausoleil ◽  
Emma L. Betty ◽  
Karen A. Stockin

The compromised state of stranded cetaceans means that euthanasia is often required. However, current knowledge and implementation of euthanasia methods remain highly variable, with limited data on the practicalities and welfare impacts of procedures. This study evaluated the available published data on cetacean euthanasia, highlighting knowledge gaps and providing direction to improve stranded cetacean welfare. A total of 2147 peer-reviewed articles describing marine mammal euthanasia were examined. Of these 3.1% provided details on the method used, with 91% employing chemical methods. Two countries, the United Kingdom (UK) and New Zealand (NZ), provided euthanasia reports to the International Whaling Commission (IWC) between 2007 and 2020. Methods employed were reported for 78.3% and 100% of individual cetaceans euthanised in the UK and NZ, respectively. In the UK, chemical euthanasia was most common (52%), whilst in NZ only ballistics methods were used. Few data were available about time to death/insensibility (TTD); 0.5% of peer-reviewed articles provided TTD, whilst TTD was reported for 35% of individuals in the UK and for 98% in NZ. However, IWC reports lacked detail on how death/insensibility were assessed, with multiple individuals “presumed instantly” killed. Overall, the findings highlight the lack of available information on cetacean euthanasia, and suggest increased data collection and the application of appropriate methods to improve welfare.


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