pinecone/core-2020-05-10-deduplication huggingface dataset:
Rearrangement of mitochondrial pyruvate dehydrogenase subunit dihydrolipoamide dehydrogenase protein–protein interactions by the MDM2 ligand nutlin-3

Drugs targeting MDM2's hydrophobic pocket activate p53. However, these agents act allosterically and have agonist effects on MDM2's protein interaction landscape. Dominant p53-independent MDM2-drug responsive-binding proteins have not been stratified. We used as a variable the differential expression of MDM2 protein as a function of cell density to identify Nutlin-3 responsive MDM2-binding proteins that are perturbed independent of cell density using SWATH-MS. Dihydrolipoamide dehydrogenase, the E3 subunit of the mitochondrial pyruvate dehydrogenase complex, was one of two Nutlin-3 perturbed proteins identified fours hour posttreatment at two cell densities. Immunoblotting confirmed that dihydrolipoamide dehydrogenase was induced by Nutlin-3. Depletion of MDM2 using siRNA also elevated dihydrolipoamide dehydrogenase in Nutlin-3 treated cells. Mitotracker confirmed that Nutlin-3 inhibits mitochondrial activity. Enrichment of mitochondria using TOM22+ immunobeads and TMT labeling defined key changes in the mitochondrial proteome after Nutlin-3 treatment. Proximity ligation identified rearrangements of cellular protein–protein complexes in situ. In response to Nutlin-3, a reduction of dihydrolipoamide dehydrogenase/dihydrolipoamide acetyltransferase protein complexes highlighted a disruption of the pyruvate dehydrogenase complex. This coincides with an increase in MDM2/dihydrolipoamide dehydrogenase complexes in the nucleus that was further enhanced by the nuclear export inhibitor Leptomycin B. The data suggest one therapeutic impact of MDM2 drugs might be on the early perturbation of specific protein–protein interactions within the mitochondria. This methodology forms a blueprint for biomarker discovery that can identify rearrangements of MDM2 protein–protein complexes in drug-treated cells
Tackling aspecific side reactions during histone propionylation: the promise of reversing overpropionylation

Histone proteins are essential elements for DNA packaging. Moreover, the PTMs that are extremely abundant on these proteins, contribute in modeling chromatin structure and recruiting enzymes involved in gene regulation, DNA repair and chromosome condensation. This fundamental aspect, together with the epigenetic inheritance of histone PTMs, underlines the importance of having biochemical techniques for their characterization. Over the past two decades, significant improvements in mass accuracy and resolution of mass spectrometers have made LC-coupled MS the strategy of choice for accurate identification and quantification of protein PTMs. Nevertheless, in previous work we disclosed the limitations and biases of the most widely adopted sample preparation protocols for histone propionylation, required prior to bottom-up MS analysis. In this work, however, we put forward a new specific and efficient propionylation strategy by means of propionic anhydride. In this method, aspecific overpropionylation at serine (S), threonine (T) and tyrosine (Y) is reversed by adding hydroxylamine (HA). We recommend using this method for future analysis of histones through bottom-up MS
Meet the neighbours: mapping local protein interactomes by proximity-dependent labelling with BioID

Proximity-dependent biotin identification (BioID) is a recently developed method that allows the identification of proteins in the close vicinity of a protein of interest in living cells. BioID relies on fusion of the protein of interest with a mutant form of the biotin ligase enzyme BirA (BirA*) that is capable of promiscuously biotinylating proximal proteins irrespective of whether these interact directly or indirectly with the fusion protein or are merely located in the same sub-cellular neighbourhood. The covalent addition of biotin allows the labelled proteins to be purified from cell extracts on the basis of their affinity for streptavidin and identified by mass spectrometry. To date, BioID has been successfully applied to study a variety of proteins and processes in mammalian cells and unicellular eukaryotes and has been shown to be particularly suited to the study of insoluble or inaccessible cellular structures and for detecting weak or transient protein associations. Here, we provide an introduction to BioID, together with a detailed summary of where and how the method has been applied to date, and briefly discuss technical aspects involved in the planning and execution of a BioID study.Publisher PDFPeer reviewe
Proteomic characterization of microdissected breast tissue environment provides a protein-level overview of malignant transformation

Both healthy and cancerous breast tissue is heterogeneous, which is a bottleneck for proteomics-based biomarker analysis, as it obscures the cellular origin of a measured protein. We therefore aimed at obtaining a protein-level interpretation of malignant transformation through global proteome analysis of a variety of laser capture microdissected cells originating from benign and malignant breast tissues. We compared proteomic differences between these tissues, both from cells of epithelial origin and the stromal environment, and performed string analysis. Differences in protein abundances corresponded with several hallmarks of cancer, including loss of cell adhesion, transformation to a migratory phenotype, and enhanced energy metabolism. Furthermore, despite enriching for (tumor) epithelial cells, many changes to the extracellular matrix were detected in microdissected cells of epithelial origin. The stromal compartment was heterogeneous and richer in the number of fibroblast and immune cells in malignant sections, compared to benign tissue sections. Furthermore, stroma could be clearly divided into reactive and nonreactive based on extracellular matrix disassembly proteins. We conclude that proteomics analysis of both microdissected epithelium and stroma gives an additional layer of information and more detailed insight into malignant transformation
Extracting histones for the specific purpose of label-free MS

Extracting histones from cells is the first step in studies that aim to characterize histones and their post-translational modifications (hPTMs) with MS. In the last decade, label-free quantification is more frequently being used for MS-based histone characterization. However, many histone extraction protocols were not specifically designed for label-free MS. While label-free quantification has its advantages, it is also very susceptible to technical variation. Here, we adjust an established histone extraction protocol according to general label-free MS guidelines with a specific focus on minimizing sample handling. These protocols are first evaluated using SDS-PAGE. Hereafter, a selection of extraction protocols was used in a complete histone workflow for label-free MS. All protocols display nearly identical relative quantification of hPTMs. We thus show that, depending on the cell type under investigation and at the cost of some additional contaminating proteins, minimizing sample handling can be done during histone isolation. This allows analyzing bigger sample batches, leads to reduced technical variation and minimizes the chance of in vitro alterations to the hPTM snapshot. Overall, these results allow researchers to determine the best protocol depending on the resources and goal of their specific study. Data are available via ProteomeXchange with identifier PXD002885
Comparison of fractionation proteomics for local SWATH library building

For data-independent acquisition by means of sequential window acquisition of all theoretical fragment ion spectra (SWATH), a reference library of data-dependent acquisition (DDA) runs is typically used to correlate the quantitative data from the fragment ion spectra with peptide identifications. The quality and coverage of such a reference library is therefore essential when processing SWATH data. In general, library sizes can be increased by reducing the impact of DDA precursor selection with replicate runs or fractionation. However, these strategies can affect the match between the library and SWATH measurement, and thus larger library sizes do not necessarily correspond to improved SWATH quantification. Here, three fractionation strategies to increase local library size were compared to standard library building using replicate DDA injection: protein SDS-PAGE fractionation, peptide high-pH RP-HPLC fractionation and MS-acquisition gas phase fractionation. The impact of these libraries on SWATH performance was evaluated in terms of the number of extracted peptides and proteins, the match quality of the peptides and the extraction reproducibility of the transitions. These analyses were conducted using the hydrophilic proteome of differentiating human embryonic stem cells. Our results show that SWATH quantitative results and interpretations are affected by choice of fractionation technique. Data are available via ProteomeXchange with identifier PXD006190
SIMLR: A Tool for Large-Scale Genomic Analyses by Multi-Kernel Learning

We here present SIMLR (Single-cell Interpretation via Multi-kernel LeaRning),
an open-source tool that implements a novel framework to learn a
sample-to-sample similarity measure from expression data observed for
heterogenous samples. SIMLR can be effectively used to perform tasks such as
dimension reduction, clustering, and visualization of heterogeneous populations
of samples. SIMLR was benchmarked against state-of-the-art methods for these
three tasks on several public datasets, showing it to be scalable and capable
of greatly improving clustering performance, as well as providing valuable
insights by making the data more interpretable via better a visualization.
Availability and Implementation
  SIMLR is available on GitHub in both R and MATLAB implementations.
Furthermore, it is also available as an R package on http://bioconductor.org
Characterization of the proteome of Theobroma cacao beans by nano-UHPLC-ESI MS/MS

Cocoa seed storage proteins play an important role in flavour development as aroma precursors are formed from their degradation during fermentation. Major proteins in the beans of Theobroma cacao are the storage proteins belonging to the vicilin and albumin classes. Although both these classes of proteins have been extensively characterized, there is still limited information on the expression and abundance of other proteins present in cocoa beans. This work is the first attempt to characterize the whole cocoa bean proteome by nanoUHPLC-ESI MS/MS analysis using tryptic digests of cocoa bean protein extracts. The results of this analysis show that a total of 906 proteins could be identified using a species-specific Theobroma cacao database. The majority of the identified proteins were involved with metabolism and energy. Additionally, a significant number of the identified proteins were linked to protein synthesis and processing. Several proteins were also involved with plant response to stress conditions and defence. Albumin and vicilin storage proteins showed the highest intensity values among all detected proteins, although only seven entries were identified as storage proteins. A comparison of MS/MS data searches carried out against larger non-specific databases confirmed that using a species-specific database can increase the number of identified proteins, and at the same time reduce the number of false positives. The results of this work will be useful in developing tools which can allow the comparison of the proteomic profile of cocoa beans from different genotypes and geographic origins. Data are available via ProteomeXchange with identifier PXD005586
The relative importance of the PMBO guide's nine knowledge areas during project planning

Although A Guide to the Project Management
Body of Knowledge (PMBOK® Guide)—Fourth
Edition identifies nine Knowledge Areas that
project managers should focus on while managing
projects, it does not indicate the relative
importance of each of these Knowledge Areas.
However, such information can be of great significance
in helping project managers determine
how to use their available resources
most effectively. This article investigates the
relative importance of the project management
Knowledge Areas used during the planning
phase of a project and their impact on project
success. Results presented in this article are
based on a field study that involved 783 project
managers from different countries and industries.
The study revealed that the Knowledge
Areas with the greatest impact on project success
were Time, Risk, Scope, and Human
Resources. However, these results have been
found to be sensitive to the industry in which
projects were undertaken. Differences among
industries are described and discussed in the
article
Financial incentives and advanced construction procurement systems

Construction clients often use financial incentives to encourage stakeholder motivation and commitment to voluntary higher-order project goals. Despite the increased use of financial incentives, there is little literature addressing means of optimizing outcomes. Using a case study methodology, the examination of a successful Australian construction project demonstrates the features of a positively geared procurement approach that promotes the effectiveness of financial incentives. The research results show that if the incentive system is perceived to be fair and is applied to reward exceptional performance, and not to manipulate, then contractors are more likely to be positively motivated
Single-Loop Project Controls:  Reigning Paradigms or Straitjackets?

The article of record as published may be located at http://dx.doi.org/10.1002/pmj.20176This article reports on the results from an ongoing
research program to study the role mental
models play in project decision making. Project
management belongs to the class of multiloop
nonlinear feedback systems, but most managers
do not see it that way. Our experimental
results suggest that managers adopt simplistic
single-loop views of causality, ignore multiple
feedback interactions, and are insensitive to
nonlinearities. Specifically, the article examines
single-loop models of project planning and control,
discusses their limitations, and proposes
tools to address them
Blowing hot and cold on project management

The purpose of this article is to suggest a possible “meta” approach of the project management field—the unit of analysis—respectful of the various perspectives in existence, while providing an integrative ontological and epistemological framework. In order to do so, I first suggest what could be perceived as being the state of the field and its main constituting “school of thoughts.” Then I open the debate on what could be the ontological and epistemological perspectives enabling us to better take into account the diversity we face in considering the richness of the field. Based on these developments, I propose to address project management as a complex integrative knowledge field, which eventually will lead us to consider “modeling—developing specific convention—to do ingeniously” as acting and learning mode in the management of projects
The relationship between organizational and professional commitment in the case of project workers : implications for project management

The purpose of this article is to investigate the relationship between organizational and professional commitment of project workers. We first present (1) role-conflict theory and exchange theory to establish the multiple dimensions of commitment (affective, continuance, and normative) and (2) social identity theory to support our argument for different foci of commitment—organization and profession. Building on these theoretical lenses, we present the literature review that compares organizational and professional commitment of project workers with respect to the three dimensions of commitment. Adopting a positivist approach and a sample of 141 project workers, we use Pearson’s correlation to identify the relationship between affective organizational and affective professional, continuance organizational and continuance professional, and normative organizational and normative professional commitment. We report significant correlation between affective organizational commitment and affective professional commitment of project workers. The correlations between continuance organizational commitment and continuance professional commitment and normative organizational commitment and normative professional commitment are moderate. We then discuss the implications of these findings for the project management profession
Exploring PMOs Through Community of Practice Theory

This is the original article as published by PMIThis article explores project management
offices (PMOs) through community of practice
theory. Preliminary results from a national
health care case study are used to confirm the
legitimacy of this approach. Today’s knowledgebased
economy calls for mechanisms to share
knowledge. The issue of making more with less
is at stake in order to reuse good practices,
support innovative practice, and prevent the
reinvention of the wheel. Members of these communities
are at the heart of the learning process.
The originality of this research is that it sheds
light on PMOs in a new theoretical perspective
within the field of knowledge management.1,Tillatels
Measuring program success

This is the original article as published by PMIGrowth in the use of programs has led to a requirement of understanding what constitute program success. A measurement construct for program success, which comprises four dimensions, namely, delivery capability, organizational capability, marketing capability and innovative capability was developed based on 172 responses to a worldwide web-based questionnaire to program managers. Analysis of variance (ANOVA) and canonical correlation analysis were applied to test for the relationship between program success and program context. Results showed that the measurement construct for program success was stable over different types of program contexts. It provides a tool for further investigation into program success assessment.1, Tillatels
A comparative study of the benefits of applying target cost contracts between South Australia and Hong Kong

This article aims to identify and analyze the key benefits of adopting Guaranteed Maximum Price and Target Cost Contracts (GMP/TCC) over and above the traditional lump-sum contractual arrangement through an empirical questionnaire survey conducted in South Australia and compared with the findings in Hong Kong. The Mann-Whitney U Test indicated differences in perception between the two groups of respondents on the majority of the identified benefits. The study has provided an in-depth understanding of the perceived benefits of the GMP/TCC scheme, hence leading to a wider application of those alternative integrated procurement strategies in both regions for reference by the construction community at large.Department of Building and Real EstateAuthor name used in this manuscript: Patrick T. I. Lam2011-2012 > Academic research: refereed > Publication in refereed journalpreprint_postprin
Counteracting Free‐Riding With Team Morale—An Experimental Study

This study focuses on a behavioral perspective to examine the detrimental effects of free‐riding on team performance, and investigates team morale as a key factor that counteracts the tendency of free‐riding among team members. Results of the empirical test imply that enhancing team morale can effectively reduce the scale of free‐riding behavior in project teams; in addition, controlling team size also provides help to constrain the undesired behavior. The two means can be carefully applied to project management during early stages of project development before the commitment of significant resources. Implications for both research and team practices are discussed
A Relational Typology of Project Management Offices

This is the original article as published by PMI.This explorative paper develops a relational typology of PMOs based on their roles with stakeholders. A multi-case study was used to identify these roles PMOs in multiple-PMO settings. A three dimensional role space allows locating the complex relational profiles that PMOs take on in respect to their stakeholders in practice. Super-ordinate, sub-ordinate and co-equal roles were identified in a framework of servicing, controlling and partnering in organizations. While servicing (subordinate role profile) and controling (super-ordinate role profile) support organizational effectiveness and exploitation of knowledge, partnering (co-equal role profile) creates the slack necessary for potential exploration of new knowledge.1,Tillatels
The Interrelationship of Governance,Trust, and Ethics in Temporary Organizations

This study investigates the variety of ethical decisions of project managers and their impact from corporate governance and project governance structures. The roles of personal trust and system trust as a mechanism to steer ethical decision making in different governance settings is explored. Nine qualitative case studies in Europe, Asia, and Australia show that ethical decision making is contingent on trust, which in turn is contingent on the fulfillment of personal expectations within a given governance structure. The findings show the prerequisites for ethical decision making and the consequences of lack of trust. Further managerial and theoretical implications are discussed.1, Tillatels
Perspectives on the Formal Authority Between Project Managers and Change Managers

Project management and change management both contribute to the management and delivery of changes to organizations; however, they are based on distinct bodies of knowledge, and practitioners of these disciplines have disparate views on how change should be managed. There is a lack of consensus about how these disciplines should work together to deliver organizational change projects which may result in conflict. This research delves into practitioners’ perspectives on formal authority, the reporting relationship between these disciplines, and reveals the fundamental differences in how practitioners of these disciplines view the practice of organizational change
Reconnecting theory and practice in pluralistic contexts: Issues and Aristotelian considerations

The purpose of this article is to contribute, from a research practitioner perspective, to the theory–practice gap debate in organization studies, focusing on pluralistic contexts such as project organizing. The current debate is introduced; then the features of the two main philosophical traditions (i.e., modernism and postmodernism) are critically summarized. Then, propositions to reconnect theory and practice according to the Aristotelian premodern ethical and practical philosophy are discussed. Some key implications in the following areas are outlined: roles played by practitioners and scholars; emancipatory praxeological style of reasoning; closing the “phronetic gap”; and the development of “good practice,” ethics, and politics