scholarly journals Coevolution of Eukaryote-like Vps4 and ESCRT-III Subunits in the Asgard Archaea

mBio ◽  
2020 ◽  
Vol 11 (3) ◽  
Author(s):  
Zhongyi Lu ◽  
Ting Fu ◽  
Tianyi Li ◽  
Yang Liu ◽  
Siyu Zhang ◽  
...  
Keyword(s):  
Distinct Type ◽  
Dynamics Simulation ◽  
Eukaryotic Cells ◽  
Endomembrane System ◽  
Apparent Absence ◽  
Content Type ◽  
Essential Components ◽  
Functional Features ◽  
Protein Components ◽  
Functional Components

ABSTRACT The emergence of the endomembrane system is a key step in the evolution of cellular complexity during eukaryogenesis. The endosomal sorting complex required for transport (ESCRT) machinery is essential and required for the endomembrane system functions in eukaryotic cells. Recently, genes encoding eukaryote-like ESCRT protein components have been identified in the genomes of Asgard archaea, a newly proposed archaeal superphylum that is thought to include the closest extant prokaryotic relatives of eukaryotes. However, structural and functional features of Asgard ESCRT remain uncharacterized. Here, we show that Vps4, Vps2/24/46, and Vps20/32/60, the core functional components of the Asgard ESCRT, coevolved eukaryote-like structural and functional features. Phylogenetic analysis shows that Asgard Vps4, Vps2/24/46, and Vps20/32/60 are closely related to their eukaryotic counterparts. Molecular dynamics simulation and biochemical assays indicate that Asgard Vps4 contains a eukaryote-like microtubule-interacting and transport (MIT) domain that binds the distinct type 1 MIT-interacting motif and type 2 MIT-interacting motif in Vps2/24/46 and Vps20/32/60, respectively. The Asgard Vps4 partly, but much more efficiently than homologs from other archaea, complements the vps4 null mutant of Saccharomyces cerevisiae, further supporting the functional similarity between the membrane remodeling machineries of Asgard archaea and eukaryotes. Thus, this work provides evidence that the ESCRT complexes from Asgard archaea and eukaryotes are evolutionarily related and functionally similar. Thus, despite the apparent absence of endomembranes in Asgard archaea, the eukaryotic ESCRT seems to have been directly inherited from an Asgard ancestor, to become a key component of the emerging endomembrane system. IMPORTANCE The discovery of Asgard archaea has changed the existing ideas on the origins of eukaryotes. Researchers propose that eukaryotic cells evolved from Asgard archaea. This hypothesis partly stems from the presence of multiple eukaryotic signature proteins in Asgard archaea, including homologs of ESCRT proteins that are essential components of the endomembrane system in eukaryotes. However, structural and functional features of Asgard ESCRT remain unknown. Our study provides evidence that Asgard ESCRT is functionally comparable to the eukaryotic counterparts, suggesting that despite the apparent absence of endomembranes in archaea, eukaryotic ESCRT was inherited from an Asgard archaeal ancestor, alongside the emergence of endomembrane system during eukaryogenesis.

scholarly journals Co-evolution of Eukaryotic-like Vps4 and ESCRT-III Subunits in the Asgard Archaea

2020 ◽  
Author(s):  
Zhongyi Lu ◽  
Ting Fu ◽  
Tianyi Li ◽  
Yang Liu ◽  
Siyu Zhang ◽  
...  
Keyword(s):  
Distinct Type ◽  
Eukaryotic Cells ◽  
Endomembrane System ◽  
Apparent Absence ◽  
Endosomal Sorting ◽  
Essential Components ◽  
Genes Encoding ◽  
Functional Features ◽  
Protein Components ◽  
Functional Components

ABSTRACTThe emergence of the endomembrane system is a key step in the evolution of cellular complexity during eukaryogenesis. The Endosomal Sorting Complex Required for Transport (ESCRT) machinery is essential and required for the endomembrane system functions in eukaryotic cells. Recently, genes encoding eukaryote-like ESCRT protein components have been identified in the genomes of Asgard archaea, a newly proposed archaeal superphylum that is thought to include the closest extant prokaryotic relatives of eukaryotes. However, structural and functional features of Asgard ESCRT remain uncharacterized. Here we show that Vps4, Vps2/24/46, and Vps20/32/60, the core functional components of the Asgard ESCRT, co-evolved eukaryote-like structural and functional features. Phylogenetic analysis shows that Asgard Vps4, Vps2/24/46, and Vps20/32/60 are closely related to their eukaryotic counterparts. Molecular dynamic simulation and biochemical assays indicate that Asgard Vps4 contains a eukaryote-like Microtubule Interacting and Transport (MIT) domain that binds the distinct type-1 MIT Interacting Motif and type-2 MIT Interacting Motif in Vps2/24/46, and Vps20/32/60, respectively. The Asgard Vps4 partly, but much more efficiently than homologs from other archaea, complements the vps4 null mutant of Saccharomyces cerevisiae, further supporting the functional similarity between the membrane remodeling machineries of Asgard archaea and eukaryotes. Thus, this work provides evidence that the ESCRT complexes from Asgard archaea and eukaryotes are evolutionarily related and functionally similar. Thus, despite the apparent absence of endomembranes in Asgard archaea, the eukaryotic ESCRT seems to have been directly inherited from an Asgard ancestor, to become a key component of the emerging endomembrane system.IMPORTANCEThe discovery of Asgard archaea has changed the exiting ideas on the origins of Eukaryotes. Researchers propose that eukaryotic cells evolve from Asgard archaea. This hypothesis partly stems from the presence of multiple eukaryotic signature proteins in Asgard archaea, including homologues of ESCRT proteins that are essential components of the endomembrane system in eukaryotes. However, structural and functional features of Asgard ESCRT remain unknown. Our study provides evidence that Asgard ESCRT is functionally comparable to the eukaryotic counterparts suggesting that, despite the apparent absence of endomembranes in archaea, eukaryotic ESCRT was inherited from an Asgard archaeal ancestor, alongside the emergence of endomembrane system during eukaryogenesis.

scholarly journals Interaction of the Aspergillus nidulans Microtubule-Organizing Center (MTOC) Component ApsB with Gamma-Tubulin and Evidence for a Role of a Subclass of Peroxisomes in the Formation of Septal MTOCs

2010 ◽  
Vol 9 (5) ◽  
pp. 795-805 ◽  
Author(s):  
Nadine Zekert ◽  
Daniel Veith ◽  
Reinhard Fischer
Keyword(s):  
Aspergillus Nidulans ◽  
Protein Complexes ◽  
Spindle Pole ◽  
Eukaryotic Cells ◽  
Microtubule Organizing Center ◽  
Body Protein ◽  
Content Type ◽  
C Terminus ◽  
Peroxisomal Targeting ◽  
Gamma Tubulin

ABSTRACT Peroxisomes are a diverse class of organelles involved in different physiological processes in eukaryotic cells. Although proteins imported into peroxisomes carry a peroxisomal targeting sequence at the C terminus (PTS1) or an alternative one close to the N terminus (PTS2), the protein content of peroxisomes varies drastically. Here we suggest a new class of peroxisomes involved in microtubule (MT) formation. Eukaryotic cells assemble MTs from distinct points in the cell. In the fungus Aspergillus nidulans, septum-associated microtubule-organizing centers (sMTOCs) are very active in addition to the spindle pole bodies (SPBs). Previously, we identified a novel MTOC-associated protein, ApsB (Schizosaccharomyces pombe mto1), whose absence affected MT formation from sMTOCs more than from SPBs, suggesting that the two protein complexes are organized differently. We show here that sMTOCs share at least two further components, gamma-tubulin and GcpC (S. pombe Alp6) with SPBs and found that ApsB interacts with gamma-tubulin. In addition, we discovered that ApsB interacts with the Woronin body protein HexA and is targeted to a subclass of peroxisomes via a PTS2 peroxisomal targeting sequence. The PTS2 motif was necessary for function but could be replaced with a PTS1 motif at the C terminus of ApsB. These results suggest a novel function for a subclass of peroxisomes in cytoskeletal organization.

scholarly journals A Novel 6-Benzyl Ether Benzoxaborole Is Active against Mycobacterium tuberculosisIn Vitro

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Nipul Patel ◽  
Theresa O'Malley ◽  
Yong-Kang Zhang ◽  
Yi Xia ◽  
Bjorn Sunde ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Liquid Medium ◽  
Inhibitory Concentration ◽  
Solid Medium ◽  
Eukaryotic Cells ◽  
Intracellular Bacteria ◽  
Benzyl Ether ◽  
Content Type ◽  
Resistant Mutants

ABSTRACT We identified a novel 6-benzyl ether benzoxaborole with potent activity against Mycobacterium tuberculosis. The compound had an MIC of 2 μM in liquid medium. The compound was also able to prevent growth on solid medium at 0.8 μM and was active against intracellular bacteria (50% inhibitory concentration [IC50] = 3.6 μM) without cytotoxicity against eukaryotic cells (IC50 > 100 μM). We isolated resistant mutants (MIC ≥ 100 μM), which had mutations in Rv1683, Rv3068c, and Rv0047c.

Stairways to heaven: implementing social media in organizations

2013 ◽  
Vol 17 (5) ◽  
pp. 741-754 ◽  
Author(s):  
Moria Levy
Keyword(s):  
Social Media ◽  
Knowledge Management ◽  
Empirical Study ◽  
Design Methodology ◽  
Applied Research ◽  
Service Marketing ◽  
Content Type ◽  
Four Levels ◽  
Functional Components ◽  
Practical Implications

Purpose – This paper is aimed at both researchers and organizations. For researchers, it seeks to provide a means for better analyzing the phenomenon of social media implementation in organizations as a knowledge management (KM) enabler. For organizations, it seeks to suggest a step-by-step architecture for practically implementing social media and benefiting from it in terms of KM. Design/methodology/approach – The research is an empirical study. A hypothesis was set; empirical evidence was collected (from 34 organizations). The data were analyzed both quantitatively and qualitatively, thereby forming the basis for the proposed architecture. Findings – Implementing social media in organizations is more than a yes/no question; findings show various levels of implementation in organizations: some implementing at all levels, while others implement only tools, functional components, or even only visibility. Research limitations/implications – Two main themes should be further tested: whether the suggested architecture actually yields faster/eased KM implementation compared to other techniques; and whether it can serve needs beyond the original scope (KM, Israel) as tested in this study (i.e. also for other regions and other needs – service, marketing and sales, etc.). Practical implications – Organizations can use the suggested four levels architecture as a guideline for implementing social media as part of their KM efforts. Originality/value – This paper is original and innovative. Previous studies describe the implementation of social media in terms of yes/no; this research explores the issue as a graded one, where organizations can and do implement social media step-by-step. The paper's value is twofold: it can serve as a foundational study for future researches, which can base their analysis on the suggested architecture of four levels of implementation. It also serves as applied research that will help organizations searching for social media implementation KM enablers.

The role of robotics in additive manufacturing: review of the AM processes and introduction of an intelligent system

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
J. Norberto Pires ◽  
Amin S. Azar ◽  
Filipe Nogueira ◽  
Carlos Ye Zhu ◽  
Ricardo Branco ◽  
...  
Keyword(s):  
Additive Manufacturing ◽  
Computer Aided Design ◽  
Intelligent System ◽  
Material Selection ◽  
High Strength Steels ◽  
Industrial Applications ◽  
Layer By Layer ◽  
Content Type ◽  
Functional Components

Purpose Additive manufacturing (AM) is a rapidly evolving manufacturing process, which refers to a set of technologies that add materials layer-by-layer to create functional components. AM technologies have received an enormous attention from both academia and industry, and they are being successfully used in various applications, such as rapid prototyping, tooling, direct manufacturing and repair, among others. AM does not necessarily imply building parts, as it also refers to innovation in materials, system and part designs, novel combination of properties and interplay between systems and materials. The most exciting features of AM are related to the development of radically new systems and materials that can be used in advanced products with the aim of reducing costs, manufacturing difficulties, weight, waste and energy consumption. It is essential to develop an advanced production system that assists the user through the process, from the computer-aided design model to functional components. The challenges faced in the research and development and operational phase of producing those parts include requiring the capacity to simulate and observe the building process and, more importantly, being able to introduce the production changes in a real-time fashion. This paper aims to review the role of robotics in various AM technologies to underline its importance, followed by an introduction of a novel and intelligent system for directed energy deposition (DED) technology. Design/methodology/approach AM presents intrinsic advantages when compared to the conventional processes. Nevertheless, its industrial integration remains as a challenge due to equipment and process complexities. DED technologies are among the most sophisticated concepts that have the potential of transforming the current material processing practices. Findings The objective of this paper is identifying the fundamental features of an intelligent DED platform, capable of handling the science and operational aspects of the advanced AM applications. Consequently, we introduce and discuss a novel robotic AM system, designed for processing metals and alloys such as aluminium alloys, high-strength steels, stainless steels, titanium alloys, magnesium alloys, nickel-based superalloys and other metallic alloys for various applications. A few demonstrators are presented and briefly discussed, to present the usefulness of the introduced system and underlying concept. The main design objective of the presented intelligent robotic AM system is to implement a design-and-produce strategy. This means that the system should allow the user to focus on the knowledge-based tasks, e.g. the tasks of designing the part, material selection, simulating the deposition process and anticipating the metallurgical properties of the final part, as the rest would be handled automatically. Research limitations/implications This paper reviews a few AM technologies, where robotics is a central part of the process, such as vat photopolymerization, material jetting, binder jetting, material extrusion, powder bed fusion, DED and sheet lamination. This paper aims to influence the development of robot-based AM systems for industrial applications such as part production, automotive, medical, aerospace and defence sectors. Originality/value The presented intelligent system is an original development that is designed and built by the co-authors J. Norberto Pires, Amin S. Azar and Trayana Tankova.

Perceptions, reality and semantics: exploring perceptions of coaching and academic advising as distinct roles

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Alicia Sepulveda ◽  
Matthew Birnbaum
Keyword(s):  
Higher Education ◽  
United States ◽  
Academic Advising ◽  
Distinct Type ◽  
The United States ◽  
Research Approach ◽  
Clear Understanding ◽  
Academic Coaching ◽  
Content Type ◽  
Practical Implications

PurposeCoaching in higher education has become increasingly common across the United States. Our qualitative study explores the perceptions of coaches and advisors, as they consider academic coaching as a role distinct from academic advising.Design/methodology/approachOur study adopts a qualitative research approach. Two focus groups were conducted with 14 coaching and academic advising professionals.FindingsOur findings identify at least three major themes when considering academic coaching as a role distinct from academic advising: (1) Potential role overlap, (2) Caseload disparities and (3) Philosophical differences. The indiscriminate use of the title of “coach” contributed to confusion, ambiguity and tension.Practical implicationsWithout a clear understanding of the coach role as a distinct type of support in higher education, confusion and ambiguity are likely to continue.Originality/valueNo studies have explored the perceptions of coaches and advisors, as they consider academic coaching as a role distinct in the United States.

scholarly journals The Phosphohistidine Phosphatase SixA Targets a Phosphotransferase System

mBio ◽  
2018 ◽  
Vol 9 (6) ◽  
Author(s):  
Jane E. Schulte ◽  
Mark Goulian
Keyword(s):  
Escherichia Coli ◽  
Protein Phosphatases ◽  
Growth Defect ◽  
Phosphotransferase System ◽  
Protein Activity ◽  
Content Type ◽  
Bacterial Physiology ◽  
Phosphoryl Groups ◽  
Regulate Protein ◽  
Protein Components

ABSTRACTSixA, a well-conserved protein found in proteobacteria, actinobacteria, and cyanobacteria, is the only reported example of a bacterial phosphohistidine phosphatase. A single protein target of SixA has been reported to date: theEscherichia colihistidine kinase ArcB. The present work analyzes an ArcB-independent growth defect of asixAdeletion inE. coli. A screen for suppressors, analysis of various mutants, and phosphorylation assays indicate that SixA modulates phosphorylation of the nitrogen-related phosphotransferase system (PTSNtr). The PTSNtris a widely conserved bacterial pathway that regulates diverse metabolic processes through the phosphorylation states of its protein components, EINtr, NPr, and EIIANtr, which receive phosphoryl groups on histidine residues. However, a mechanism for dephosphorylating this system has not been reported. The results presented here suggest a model in which SixA removes phosphoryl groups from the PTSNtrby acting on NPr. This work uncovers a new role for the phosphohistidine phosphatase SixA and, through factors that affect SixA expression or activity, may point to additional inputs that regulate the PTSNtr.IMPORTANCEOne common means to regulate protein activity is through phosphorylation. Protein phosphatases exist to reverse this process, returning the protein to the unphosphorylated form. The vast majority of protein phosphatases that have been identified target phosphoserine, phosphotheronine, and phosphotyrosine. A widely conserved phosphohistidine phosphatase was identified inEscherichia coli20 years ago but remains relatively understudied. The present work shows that this phosphatase modulates the nitrogen-related phosphotransferase system, a pathway that is regulated by nitrogen and carbon metabolism and affects diverse aspects of bacterial physiology. Until now, there was no known mechanism for removing phosphoryl groups from this pathway.

Complementarity effect of supply chain competencies on innovation capability

2019 ◽  
Vol 25 (6) ◽  
pp. 1251-1272 ◽  
Author(s):  
Ying Liao ◽  
Yulong Li
Keyword(s):  
Supply Chain ◽  
Structural Equation ◽  
Equation Modeling ◽  
Supply Network ◽  
Innovation Capability ◽  
Exploration And Exploitation ◽  
Complementarity Effect ◽  
Content Type ◽  
Essential Components ◽  
Network Flexibility

Purpose From the perspective of the economic theory of complementarity, the purpose of this paper is to examine how internal collaboration and external competencies would provoke and strengthen each other, and subsequently enhance organizational innovation capability. Design/methodology/approach The survey data were collected from 201 manufacturing firms and checked for common method variance, validity and reliability. Structural equation modeling was then used to test the hypothetical complementarity effect. Findings The results suggest that internal collaboration (as a manifestation of exploitative learning) and external competencies, which include supply network flexibility and supplier operational capabilities (as manifestation of exploratory learning), do in fact compensate for each other’s deficiencies. Complementary deployment of internal collaboration and external competencies enhances each other’s contribution to innovation capability. Practically, the study indicates that organizations should consider making concerted efforts to develop internal collaboration, supply network flexibility and supplier operational capability as a bundle. Originality/value Extensive discussions exist in the literature on exploration and exploitation being essential components of innovation and their conflicting impact on innovation efficiency and effectiveness. But how an organization should operationally develop supply chain competencies in order to maximize overall innovation capability still remains largely an unanswered question. The current study advances the research on the inter-relationships between exploration and exploitation by empirically demonstrating the complementary nature of internal collaboration and external competencies in developing sustainable innovation capabilities.

scholarly journals Finding Pathogenic nsSNP’s and their structural effect on COPS2 using Molecular Dynamic Approach

2020 ◽  
Author(s):  
Ashish Malik ◽  
Kajal Pande ◽  
Abhishek Kumar ◽  
Alekhya Vemula ◽  
R Madhuri ◽  
...  
Keyword(s):  
Neuronal Differentiation ◽  
Developmental Process ◽  
Normal Activity ◽  
Structural Effect ◽  
Dynamics Simulation ◽  
Cop9 Signalosome ◽  
Nucleotide Polymorphisms ◽  
Discovery Studio ◽  
Essential Components ◽  
Protein Molecular Dynamics

AbstractCOP9 Signalosome Subunit 2 is a highly conserved multiprotein complex which is involved in the cellular process and developmental process. It is one of the essential components in the COP9 Signalosome Complex (CSN). It is also involved in neuronal differentiation interacting with NIF3L1. The gene involved in neuronal differentiation is negatively regulated due to the transcription co-repressor interaction of NIF3L1 with COPS2. In the present study, we have evaluated the outcome for 90 non-synonymous single nucleotide polymorphisms (nsSNP’s) in COPS2 gene through computational tools. After the analysis, 4 SNP’s (S120C, N144S, Y159H, R173C) were found to be deleterious. The native and mutated structures were prepared using discovery studio and docked to check the interactions with NIF3L1.On the basis of ZDOCK score the top 3 mutations (N144S, Y159H, R173C) were screened out. Further to analyze the effect of amino acid substitution on the molecular structure of protein Molecular Dynamics simulation was carried out. Analysis based on RMSD, RMSF, RG, H-bond showed a significant deviation in the graph, which demonstrated conformation change and instability compared to the wild structure. As it is known mutations in COPS2 gene can disrupt the normal activity of the CSN2 protein which may cause neuronal differentiation. Our results showed N144S, Y159H and R173C mutations are to be more pathogenic and may cause disease

scholarly journals The Nuclear Export Receptors TbMex67 and TbMtr2 Are Required for Ribosome Biogenesis in Trypanosoma brucei

mSphere ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Constance Rink ◽  
Martin Ciganda ◽  
Noreen Williams
Keyword(s):  
Trypanosoma Brucei ◽  
Nuclear Export ◽  
Ribosome Biogenesis ◽  
Biological Process ◽  
Large Subunit ◽  
Critical Role ◽  
Ribosomal Subunits ◽  
Content Type ◽  
Protein Components ◽  
Export Receptors

ABSTRACT Ribosomal maturation is a complex and highly conserved biological process involving migration of a continuously changing RNP across multiple cellular compartments. A critical point in this process is the translocation of individual ribosomal subunits (60S and 40S) from the nucleus to the cytoplasm, and a number of export factors participate in this process. In this study, we characterize the functional role of the auxiliary export receptors TbMex67 and TbMtr2 in ribosome biogenesis in the parasite Trypanosoma brucei. We demonstrate that depletion of each of these proteins dramatically impacts the steady-state levels of other proteins involved in ribosome biogenesis, including the trypanosome-specific factors P34 and P37. In addition, we observe that the loss of TbMex67 or TbMtr2 leads to aberrant ribosome formation, rRNA processing, and polysome formation. Although the TbMex67-TbMtr2 heterodimer is structurally distinct from Mex67-Mtr2 complexes previously studied, our data show that they retain a conserved function in ribosome biogenesis. IMPORTANCE The nuclear export of ribosomal subunits (60S and 40S) depends in part on the activity of the essential auxiliary export receptors TbMtr2 and TbMex67. When these proteins are individually depleted from the medically and agriculturally significant parasite Trypanosoma brucei, distinct alterations in the processing of the rRNAs of the large subunit (60S) are observed as well as aberrations in the assembly of functional ribosomes (polysomes). We also established that TbMex67 and TbMtr2 interact directly or indirectly with the protein components of the 5S RNP, including the trypanosome-specific P34/P37. The critical role that TbMex67 and TbMtr2 play in this essential biological process together with their parasite-specific interactions may provide new therapeutic targets against this important parasite.

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