scholarly journals A Key Motif in the Cholesterol-Dependent Cytolysins Reveals a Large Family of Related Proteins

mBio ◽  
2020 ◽  
Vol 11 (5) ◽  
Author(s):  
Jordan C. Evans ◽  
Bronte A. Johnstone ◽  
Sara L. Lawrence ◽  
Craig J. Morton ◽  
Michelle P. Christie ◽  
...  
Keyword(s):  
Large Family ◽  
Structural Similarity ◽  
Particle Analysis ◽  
Critical Component ◽  
Content Type ◽  
Conserved Motif ◽  
Forming Mechanism ◽  
Terrestrial Environments ◽  
Pore Complexes ◽  
High Degree

ABSTRACT The cholesterol-dependent cytolysins (CDCs) are bacterial, β-barrel, pore-forming toxins. A central enigma of the pore-forming mechanism is how completion of the prepore is sensed to initiate its conversion to the pore. We identified a motif that is conserved between the CDCs and a diverse family of nearly 300 uncharacterized proteins present in over 220 species that span at least 10 bacterial and 2 eukaryotic phyla. Except for this motif, these proteins exhibit little similarity to the CDCs at the primary structure level. Studies herein show this motif is a critical component of the sensor that initiates the prepore-to-pore transition in the CDCs. We further show by crystallography, single particle analysis, and biochemical studies of one of these CDC-like (CDCL) proteins from Elizabethkingia anophelis, a commensal of the malarial mosquito midgut, that a high degree of structural similarity exists between the CDC and CDCL monomer structures and both form large oligomeric pore complexes. Furthermore, the conserved motif in the E. anophelis CDCL crystal structure occupies a nearly identical position and makes similar contacts to those observed in the structure of the archetype CDC, perfringolysin O (PFO). This suggests a common function in the CDCs and CDCLs and may explain why only this motif is conserved in the CDCLs. Hence, these studies identify a critical component of the sensor involved in initiating the prepore-to-pore transition in the CDCs, which is conserved in a large and diverse group of distant relatives of the CDCs. IMPORTANCE The cholesterol-dependent cytolysins’ pore-forming mechanism relies on the ability to sense the completion of the oligomeric prepore structure and initiate the insertion of the β-barrel pore from the assembled prepore structure. These studies show that a conserved motif is an important component of the sensor that triggers the prepore-to-pore transition and that it is conserved in a large family of previously unidentified CDC-like proteins, the genes for which are present in a vast array of microbial species that span most terrestrial environments, as well as most animal and human microbiomes. These studies establish the foundation for future investigations that will probe the contribution of this large family of CDC-like proteins to microbial survival and human disease.

scholarly journals A Comprehensive Phylogenetic and Bioinformatics Survey of Lectins in the Fungal Kingdom

2021 ◽  
Vol 7 (6) ◽  
pp. 453
Author(s):  
Annie Lebreton ◽  
François Bonnardel ◽  
Yu-Cheng Dai ◽  
Anne Imberty ◽  
Francis M. Martin ◽  
...  
Keyword(s):  
Evolutionary Relationship ◽  
Large Family ◽  
Gene Families ◽  
Carbohydrate Binding ◽  
Sequence Motifs ◽  
Fungal Lectin ◽  
Quaternary Structures ◽  
High Degree ◽  
Carbohydrate Ligand ◽  
Fungal Kingdom

Fungal lectins are a large family of carbohydrate-binding proteins with no enzymatic activity. They play fundamental biological roles in the interactions of fungi with their environment and are found in many different species across the fungal kingdom. In particular, their contribution to defense against feeders has been emphasized, and when secreted, lectins may be involved in the recognition of bacteria, fungal competitors and specific host plants. Carbohydrate specificities and quaternary structures vary widely, but evidence for an evolutionary relationship within the different classes of fungal lectins is supported by a high degree of amino acid sequence identity. The UniLectin3D database contains 194 fungal lectin 3D structures, of which 129 are characterized with a carbohydrate ligand. Using the UniLectin3D lectin classification system, 109 lectin sequence motifs were defined to screen 1223 species deposited in the genomic portal MycoCosm of the Joint Genome Institute. The resulting 33,485 putative lectin sequences are organized in MycoLec, a publicly available and searchable database. These results shed light on the evolution of the lectin gene families in fungi.

scholarly journals Greater fit and a greater gap

2019 ◽  
Vol 26 (4) ◽  
pp. 561-594
Author(s):  
Steven A. Brieger ◽  
Dirk De Clercq ◽  
Jolanda Hessels ◽  
Christian Pfeifer
Keyword(s):  
Life Satisfaction ◽  
Institutional Environment ◽  
Entrepreneurial Activity ◽  
Worker Rights ◽  
Content Type ◽  
Person Environment Fit ◽  
High Power Distance ◽  
High Degree ◽  
The Impact ◽  
Low Uncertainty

Purpose The purpose of this paper is to understand how national institutional environments contribute to differences in life satisfaction between entrepreneurs and employees. Design/methodology/approach Leveraging person–environment fit and institutional theories and using a sample of more than 70,000 entrepreneurs and employees from 43 countries, the study investigates how the impact of entrepreneurial activity on life satisfaction differs in various environmental contexts. An entrepreneur’s life satisfaction arguably should increase when a high degree of compatibility or fit exists between his or her choice to be an entrepreneur and the informal and formal institutional environment. Findings The study finds that differences in life satisfaction between entrepreneurs and employees are larger in countries with high power distance, low uncertainty avoidance, extant entrepreneurship policies, low commercial profit taxes and low worker rights. Originality/value This study sheds new light on how entrepreneurial activity affects life satisfaction, contingent on the informal and formal institutions in a country that support entrepreneurship by its residents.

Living in the end times: a short course addressing end of life issues for older people in an English parish church setting

2015 ◽  
Vol 19 (3) ◽  
pp. 140-149 ◽  
Author(s):  
Joanna Collicutt
Keyword(s):  
Older People ◽  
End Of Life ◽  
Group Dynamics ◽  
Death And Dying ◽  
Community Context ◽  
Content Type ◽  
End Of Life Issues ◽  
End Times ◽  
High Level ◽  
High Degree

Purpose – The purpose of this paper is to report a pilot study that evaluated an innovative practice in a faith community context designed to help older people live well at the end of life and prepare for death. Design/methodology/approach – A simple audit of the intervention using a contemporaneous journal kept by the author, and a follow up questionnaire completed by participants. Findings – Rich findings on the process are reported. These indicate a high degree of engagement by participants, the establishment of a high degree of group intimacy and trust, a high level of articulation of wisdom, the emergence of significant anxiety in some isolated cases, and the use made of tea and cake to manage the transition between the existentially demanding nature of the discussions and normal life. The outcome indicated very high levels of appreciation and increased confidence in relation to issues of death and dying. Practical implications – The findings of the pilot have been used to inform training of clergy in the principles of working in this area (e.g. in ways of managing group dynamics and anxiety, pacing, tuning in to archetypes and the natural symbols that people use to talk about death and dying, self-care and supervision of the programme leader/facilitator). Originality/value – The paper adds to knowledge in terms of an in depth description of processes at work in a group of older people working on spiritual and practical issues in relation to death, and offers ideas for supporting older people in this process, some of which are specific to the Christian tradition, and some of which are more widely applicable to people of all faiths and none. It gives a specific worked example of what “spiritual care” in this area might look like.

scholarly journals SfnR2 Regulates Dimethyl Sulfide-Related Utilization inPseudomonas aeruginosaPAO1

2018 ◽  
Vol 201 (4) ◽  
Author(s):  
Benjamin R. Lundgren ◽  
Zaara Sarwar ◽  
Kyle S. Feldman ◽  
Joseph M. Shoytush ◽  
Christopher T. Nomura
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Target Genes ◽  
Dimethyl Sulfide ◽  
Sulfur Compound ◽  
Main Function ◽  
Gene Encoding ◽  
Content Type ◽  
First Results ◽  
Terrestrial Environments ◽  
Initial Activation

ABSTRACTDimethyl sulfide (DMS) is a volatile sulfur compound produced mainly from the degradation of dimethylsulfoniopropionate (DMSP) in marine environments. DMS undergoes oxidation to form dimethyl sulfoxide (DMSO), dimethyl sulfone (DMSO2), and methanesulfonate (MSA), all of which occur in terrestrial environments and are accessible for consumption by various microorganisms. The purpose of the present study was to determine how the enhancer-binding proteins SfnR1 and SfnR2 contribute to the utilization of DMS and its derivatives inPseudomonas aeruginosaPAO1. First, results from cell growth experiments showed that deletion of eithersfnR2orsfnG, a gene encoding a DMSO2-monooxygenase, significantly inhibits the ability ofP. aeruginosaPAO1 to use DMSP, DMS, DMSO, and DMSO2as sulfur sources. Deletion of thesfnR1ormsuEDCgenes, which encode a MSA desulfurization pathway, did not abolish the growth ofP. aeruginosaPAO1 on any sulfur compound tested. Second, data collected from β-galactosidase assays revealed that themsuEDC-sfnR1operon and thesfnGgene are induced in response to sulfur limitation or nonpreferred sulfur sources, such as DMSP, DMS, and DMSO, etc. Importantly, SfnR2 (and not SfnR1) is essential for this induction. Expression ofsfnR2is induced under sulfur limitation but independently of SfnR1 or SfnR2. Finally, the results of this study suggest that the main function of SfnR2 is to direct the initial activation of themsuEDC-sfnR1operon in response to sulfur limitation or nonpreferred sulfur sources. Once expressed, SfnR1 contributes to the expression ofmsuEDC-sfnR1,sfnG, and other target genes involved in DMS-related metabolism inP. aeruginosaPAO1.IMPORTANCEDimethyl sulfide (DMS) is an important environmental source of sulfur, carbon, and/or energy for microorganisms. For various bacteria, includingPseudomonas,Xanthomonas, andAzotobacter, DMS utilization is thought to be controlled by the transcriptional regulator SfnR. Adding more complexity, some bacteria, such asAcinetobacter baumannii,Enterobacter cloacae, andPseudomonas aeruginosa, possess two, nonidentical SfnR proteins. In this study, we demonstrate that SfnR2 and not SfnR1 is the principal regulator of DMS metabolism inP. aeruginosaPAO1. Results suggest that SfnR1 has a supportive but nonessential role in the positive regulation of genes required for DMS utilization. This study not only enhances our understanding of SfnR regulation but, importantly, also provides a framework for addressing gene regulation through dual SfnR proteins in other bacteria.

scholarly journals Contrasting Patterns of Virus Protection and Functional Incompatibility Genes in Two ConspecificWolbachiaStrains fromDrosophila pandora

2018 ◽  
Vol 85 (5) ◽  
Author(s):  
Angelique K. Asselin ◽  
Simon Villegas-Ospina ◽  
Ary A. Hoffmann ◽  
Jeremy C. Brownlie ◽  
Karyn N. Johnson
Keyword(s):  
Disease Transmission ◽  
Cytoplasmic Incompatibility ◽  
Natural Populations ◽  
Differential Protection ◽  
Content Type ◽  
Infection Dynamics ◽  
Modification Factor ◽  
Control Disease ◽  
Multiple Strains ◽  
High Degree

ABSTRACTWolbachiainfections can present different phenotypes in hosts, including different forms of reproductive manipulation and antiviral protection, which may influence infection dynamics within host populations. In populations ofDrosophila pandoratwo distinctWolbachiastrains coexist, each manipulating host reproduction: strainwPanCI causes cytoplasmic incompatibility (CI), whereas strainwPanMK causes male killing (MK). CI occurs when aWolbachia-infected male mates with a female not infected with a compatible type ofWolbachia, leading to nonviable offspring.wPanMK can rescuewPanCI-induced CI but is unable to induce CI. The antiviral protection phenotypes provided by thewPanCI andwPanMK infections were characterized; the strains showed differential protection phenotypes, whereby cricket paralysis virus (CrPV)-induced mortality was delayed in flies infected withwPanMK but enhanced in flies infected withwPanCI compared to their respectiveWolbachia-cured counterparts. Homologs of thecifAandcifBgenes involved in CI identified inwPanMK andwPanCI showed a high degree of conservation; however, the CifB protein inwPanMK is truncated and is likely nonfunctional. The presence of a likely functional CifA inwPanMK andwPanMK’s ability to rescuewPanCI-induced CI are consistent with the recent confirmation of CifA’s involvement in CI rescue, and the absence of a functional CifB protein further supports its involvement as a CI modification factor. Taken together, these findings indicate thatwPanCI andwPanMK have different relationships with their hosts in terms of their protective and CI phenotypes. It is therefore likely that different factors influence the prevalence and dynamics of these coinfections in naturalDrosophila pandorahosts.IMPORTANCEWolbachiastrains are common endosymbionts in insects, with multiple strains often coexisting in the same species. The coexistence of multiple strains is poorly understood but may rely onWolbachiaorganisms having diverse phenotypic effects on their hosts. AsWolbachiais increasingly being developed as a tool to control disease transmission and suppress pest populations, it is important to understand the ways in which multipleWolbachiastrains persist in natural populations and how these might then be manipulated. We have therefore investigated viral protection and the molecular basis of cytoplasmic incompatibility in two coexistingWolbachiastrains with contrasting effects on host reproduction.

scholarly journals Structural Similarities and Differences between Two Functionally Distinct SecA Proteins, Mycobacterium tuberculosis SecA1 and SecA2

2015 ◽  
Vol 198 (4) ◽  
pp. 720-730 ◽  
Author(s):  
Stephanie Swanson ◽  
Thomas R. Ioerger ◽  
Nathan W. Rigel ◽  
Brittany K. Miller ◽  
Miriam Braunstein ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Signal Peptide ◽  
Protein A ◽  
Structural Difference ◽  
Structural Similarity ◽  
Structural Features ◽  
Dominant Negative ◽  
Content Type ◽  
Functional Regions ◽  
Suppressor Mutations

ABSTRACTWhile SecA is the ATPase component of the major bacterial secretory (Sec) system, mycobacteria and some Gram-positive pathogens have a second paralog, SecA2. In bacteria with two SecA paralogs, each SecA is functionally distinct, and they cannot compensate for one another. Compared to SecA1, SecA2 exports a distinct and smaller set of substrates, some of which have roles in virulence. In the mycobacterial system, some SecA2-dependent substrates lack a signal peptide, while others contain a signal peptide but possess features in the mature protein that necessitate a role for SecA2 in their export. It is unclear how SecA2 functions in protein export, and one open question is whether SecA2 works with the canonical SecYEG channel to export proteins. In this study, we report the structure ofMycobacterium tuberculosisSecA2 (MtbSecA2), which is the first structure of any SecA2 protein. A high level of structural similarity is observed between SecA2 and SecA1. The major structural difference is the absence of the helical wing domain, which is likely to play a role in howMtbSecA2 recognizes its unique substrates. Importantly, structural features critical to the interaction between SecA1 and SecYEG are preserved in SecA2. Furthermore, suppressor mutations of a dominant-negativesecA2mutant map to the surface of SecA2 and help identify functional regions of SecA2 that may promote interactions with SecYEG or the translocating polypeptide substrate. These results support a model in which the mycobacterial SecA2 works with SecYEG.IMPORTANCESecA2 is a paralog of SecA1, which is the ATPase of the canonical bacterial Sec secretion system. SecA2 has a nonredundant function with SecA1, and SecA2 exports a distinct and smaller set of substrates than SecA1. This work reports the crystal structure of SecA2 ofMycobacterium tuberculosis(the first SecA2 structure reported for any organism). Many of the structural features of SecA1 are conserved in the SecA2 structure, including putative contacts with the SecYEG channel. Several structural differences are also identified that could relate to the unique function and selectivity of SecA2. Suppressor mutations of asecA2mutant map to the surface of SecA2 and help identify functional regions of SecA2 that may promote interactions with SecYEG.

Audiological Features and Mitochondrial DNA Sequence in a Large Family Carrying Mitochondrial A1555G Mutation without Use of Aminoglycoside

2005 ◽  
Vol 114 (2) ◽  
pp. 153-160 ◽  
Author(s):  
Tatsuo Matsunaga ◽  
Hiroshi Kumanomido ◽  
Yu-ichi Goto ◽  
Masae Shiroma ◽  
Shin-ichi Usami
Keyword(s):  
Hearing Loss ◽  
Mitochondrial Dna ◽  
Dna Sequences ◽  
Large Family ◽  
Outer Hair Cells ◽  
Japanese Family ◽  
A1555g Mutation ◽  
Genetic Mechanisms ◽  
High Degree ◽  
Sibling Group

To elucidate the pathophysiological and genetic mechanisms of hearing loss associated with the homoplasmic mitochondrial A1555G mutation in the absence of aminoglycoside exposure, we conducted audiological and genetic analyses on 67 maternally related members of a large Japanese family carrying this mutation. A consistent pattern was evident in the audiograms, with features of sensory presbycusis, cochlear origin at all levels of hearing loss, and a high degree of vulnerability of outer hair cells. That the degree of hearing loss was similar in affected subjects within the same sibling group but differed between sibling groups suggests the involvement of nuclear modifier genes. Total mitochondrial DNA sequences were completely identical among subjects with various levels of hearing loss, and lacked additional pathogenic mutations. For the diagnosis of sensorineural hearing loss, the mitochondrial A1555G mutation should be considered when these features are present even in the absence of aminoglycoside exposure.

scholarly journals Homelessness and integrated care: an application of integrated care knowledge to understanding services for wicked issues

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Michael Clark ◽  
Michelle Cornes ◽  
Martin Whiteford ◽  
Robert Aldridge ◽  
Elizabeth Biswell ◽  
...  
Keyword(s):  
Integrated Care ◽  
Hospital Discharge ◽  
Secondary Analysis ◽  
Policy Issue ◽  
Content Type ◽  
Complex Needs ◽  
Integration Of Services ◽  
Key Issues ◽  
Discharge From Hospital ◽  
High Degree

PurposePeople experiencing homelessness often have complex needs requiring a range of support. These may include health problems (physical illness, mental health and/or substance misuse) as well as social, financial and housing needs. Addressing these issues requires a high degree of coordination amongst services. It is, thus, an example of a wicked policy issue. The purpose of this paper is to examine the challenge of integrating care in this context using evidence from an evaluation of English hospital discharge services for people experiencing homelessness.Design/methodology/approachThe paper undertakes secondary analysis of qualitative data from a mixed methods evaluation of hospital discharge schemes and uses an established framework for understanding integrated care, the Rainbow Model of Integrated Care (RMIC), to help examine the complexities of integration in this area.FindingsSupporting people experiencing homelessness to have a good discharge from hospital was confirmed as a wicked policy issue. The RMIC provided a strong framework for exploring the concept of integration, demonstrating how intertwined the elements of the framework are and, hence, that solutions need to be holistically organised across the RMIC. Limitations to integration were also highlighted, such as shortages of suitable accommodation and the impacts of policies in aligned areas of the welfare state.Research limitations/implicationsThe data for this secondary analysis were not specifically focussed on integration which meant the themes in the RMIC could not be explored directly nor in as much depth. However, important issues raised in the data directly related to integration of support, and the RMIC emerged as a helpful organising framework for understanding integration in this wicked policy context.Practical implicationsIntegration is happening in services directly concerned with the discharge from hospital of people experiencing homelessness. Key challenges to this integration are reported in terms of the RMIC, which would be a helpful framework for planning better integrated care for this area of practice.Social implicationsAddressing homelessness not only requires careful planning of integration of services at specific pathway points, such as hospital discharge, but also integration across wider systems. A complex set of challenges are discussed to help with planning the better integration desired, and the RMIC was seen as a helpful framework for thinking about key issues and their interactions.Originality/valueThis paper examines an application of integrated care knowledge to a key complex, or wicked policy issue.

scholarly journals Complete Genome Sequences of Two Salmonella Viruses, VSe11 and VSe102 (Family Myoviridae, Subfamily Ounavirinae), with a Very High Degree of Similarity

2018 ◽  
Vol 6 (21) ◽  
Author(s):  
Nikolay V. Volozhantsev ◽  
Egor A. Denisenko ◽  
Angelina A. Kislichkina ◽  
Vera P. Myakinina ◽  
Valentina M. Krasilnikova ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Complete Genome ◽  
Genome Sequences ◽  
Coding Sequences ◽  
Content Type ◽  
Double Stranded Dna ◽  
Poultry Farms ◽  
High Degree ◽  
Degree Of Similarity ◽  
Very High

ABSTRACT Two lytic double-stranded DNA bacteriophages, VSe11 and VSe102, infecting broad-spectrum Salmonella enterica were isolated from the sewage of two different poultry farms. The phage genomes comprise 86,360 bp and 86,365 bp, respectively, with a G+C content of 39.0%, and both contain 129 putative coding sequences.

Antecedents of frontline manager handling relationship conflicts

2018 ◽  
Vol 29 (1) ◽  
pp. 2-23 ◽  
Author(s):  
Yasir Tanveer ◽  
Qi Jiayin ◽  
Umair Akram ◽  
Anum Tariq
Keyword(s):  
Leadership Styles ◽  
Textile Industry ◽  
Content Type ◽  
Interpersonal Conflicts ◽  
Relationship Conflicts ◽  
Conflict Handling ◽  
High Degree ◽  
The Relationship ◽  
Frontline Managers ◽  
Practical Implications

Purpose Conflicts are inevitable in organizations and are a significant challenge for frontline managers (FLMs). This study aims to investigate the relationship between the leadership styles of FLMs and relationship conflicts (RLCs), with the indirect intervention of emotion regulation (ER) and five conflict-handling styles (CHSs). Design/methodology/approach Research data were obtained from 243 FLMs in the Pakistan textile industry. SPSS 23 and PROCESS macros software were used to test and verify hypotheses regarding leadership styles, ER, CHSs and RLC. The authors conducted 5,000 bootstrap replications to verify mediation. Findings Leadership styles are significantly associated with RLC. A high degree of ER can negatively moderate RLCs through transformational leadership (TFL) and transactional leadership (TCL) styles and positively moderate RLCs through a laissez-faire leadership (LZF) style. Among CHSs, a compromise style mediates the relationship between RLC and the TFL and LZF styles, and a domination style mediates the relationship between RLC and the TCL style. Practical implications FLMs should be trained to overcome workplace interpersonal conflicts. Appropriate cognizance of a conflict before it occurs is a requisite skill. FLMs must be able to use all five given CHSs. Originality/value This study identifies the association of leadership styles with CHSs and ER to manage RLC in a non-Western context. The study enhances understanding of the use of the ER factor with the different CHSs of FLMs.

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