scholarly journals Protein Complex Organization Imposes Constraints on Proteome Dysregulation in Cancer

2021 ◽  
Vol 1 ◽  
Author(s):  
Gökçe Senger ◽  
Martin H. Schaefer
Keyword(s):  
Dynamic Process ◽  
Protein Complex ◽  
Complex Function ◽  
Protein Assembly ◽  
Protein Abundance ◽  
Differential Protein ◽  
Proteomic Data ◽  
Abundance Patterns ◽  
Complex Organization

Protein assembly is a highly dynamic process and proteins can interact in different ways and stoichiometries within a complex. The importance of maintaining protein stoichiometry for complex function and avoiding aggregation of orphan subunits has been demonstrated. However, how exactly the organization of proteins into complexes constrains differential protein abundance in extreme cellular conditions like cancer, where a lot of protein abundance changes occur, has not been systematically investigated. To study this, we collected proteomic data made available by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) to quantify proteomic changes during carcinogenesis and systematically tested five interaction types in complexes to investigate which of these features impact on protein abundance correlation patterns in cancer. We found that higher than expected fraction of protein complex subunits does not show changes in their abundances compared to those in the normal samples. Furthermore, we found that the way proteins interact in complexes indeed constrains their co-abundance patterns. Our results highlight the role of the interactions between the proteins and the need of cancer cells to deal with aberrant changes in protein abundance.

RoDiCE: robust differential protein co-expression analysis for cancer complexome

2021 ◽  
Author(s):  
Yusuke Matsui ◽  
Yuichi Abe ◽  
Kohei Uno ◽  
Satoru Miyano
Keyword(s):  
Protein Complex ◽  
Drug Targets ◽  
Large Scale ◽  
Protein Complexes ◽  
Specific Protein ◽  
Identification Accuracy ◽  
Supplementary Information ◽  
Full Spectrum ◽  
Differential Protein ◽  
Proteomic Data

Abstract Motivation The full spectrum of abnormalities in cancer-associated protein complexes remains largely unknown. Comparing the co-expression structure of each protein complex between tumor and healthy cells may provide insights regarding cancer-specific protein dysfunction. However, the technical limitations of mass spectrometry-based proteomics, including contamination with biological protein variants, causes noise that leads to non-negligible over- (or under-) estimating co-expression. Results We propose a robust algorithm for identifying protein complex aberrations in cancer based on differential protein co-expression testing. Our method based on a copula is sufficient for improving identification accuracy with noisy data compared to conventional linear correlation-based approaches. As an application, we use large-scale proteomic data from renal cancer to show that important protein complexes, regulatory signaling pathways and drug targets can be identified. The proposed approach surpasses traditional linear correlations to provide insights into higher-order differential co-expression structures. Availability and implementation https://github.com/ymatts/RoDiCE. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals The Pivotal Player: Components of NF-κB Pathway as Promising Biomarkers in Colorectal Cancer

2021 ◽  
Vol 22 (14) ◽  
pp. 7429
Author(s):  
Matthew Martin ◽  
Mengyao Sun ◽  
Aishat Motolani ◽  
Tao Lu
Keyword(s):  
Colorectal Cancer ◽  
Biological Response ◽  
Significant Progress ◽  
Therapeutic Approaches ◽  
Successful Development ◽  
Diagnostic Screening ◽  
Proteomic Data ◽  
Large Groups ◽  
Made In

Over the last several decades, colorectal cancer (CRC) has been one of the most prevalent cancers. While significant progress has been made in both diagnostic screening and therapeutic approaches, a large knowledge gap still remains regarding the early identification and treatment of CRC. Specifically, identification of CRC biomarkers that can help with the creation of targeted therapies as well as increasing the ability for clinicians to predict the biological response of a patient to therapeutics, is of particular importance. This review provides an overview of CRC and its progression stages, as well as the basic types of CRC biomarkers. We then lay out the synopsis of signaling pathways related to CRC, and further highlight the pivotal and multifaceted role of nuclear factor (NF) κB signaling in CRC. Particularly, we bring forth knowledge regarding the tumor microenvironment (TME) in CRC, and its complex interaction with cancer cells. We also provide examples of NF-κB signaling-related CRC biomarkers, and ongoing efforts made at targeting NF-κB signaling in CRC treatment. We conclude and anticipate that with more emerging novel regulators of the NF-κB pathway being discovered, together with their in-depth characterization and the integration of large groups of genomic, transcriptomic and proteomic data, the day of successful development of more ideal NF-κB inhibitors is fast approaching.

scholarly journals Potential role of IFN-γ and IL-5 in sepsis prediction of preterm neonates

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 139-145
Author(s):  
Jelena Vucic ◽  
Miodrag Vucic ◽  
Tatjana Stankovic ◽  
Hristina Stamenkovic ◽  
Sandra Stankovic ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Late Onset ◽  
Complex Function ◽  
Preterm Neonates ◽  
Control Group ◽  
Premature Neonates ◽  
Early Onset Sepsis ◽  
Ifn Γ ◽  
Venous Plasma

Abstract Not fully maturated immune system in preterm neonates may contribute to the increased susceptibility to infection. The levels of some cytokines can be useful in the prediction and diagnosis of sepsis in premature neonates. In the present study, we evaluated the potential predictive role of IFN-γ and IL-5 in cord and venous blood, together with the determination of C-reactive protein and procalcitonin (PCT) for sepsis development in premature neonates. A total of 80 participants were included. The laboratory results and clinical histories showed that 21 participants had sepsis. Early onset sepsis was detected in 3 patients while late onset sepsis was observed in 18 participants. The venous plasma levels of IFN-γ and PCT was markedly increased in sepsis groups when compared to the participants without sepsis. On the other hand, levels of IL-5 did not significantly change in the evaluated groups of sepsis and in the control group of participants. Simultaneously, plasma venous levels were not altered in any of the evaluated groups. Obtained findings suggest that venous plasma levels of IFN-γ, rather than levels of IFN-γ in cord blood plasma, and PCT may have predictive potential for sepsis development in preterm neonates. Further studies are necessary to get more comprehension of the complex function of cytokines for sepsis development in preterm neonates.

scholarly journals Reduced Translocation Is Associated with Tolerance of Common Lambsquarters (Chenopodium album) to Glyphosate

Weed Science ◽  
2013 ◽  
Vol 61 (3) ◽  
pp. 353-360 ◽  
Author(s):  
Melinda K. Yerka ◽  
Andrew T. Wiersma ◽  
R. Bradley Lindenmayer ◽  
Philip Westra ◽  
William G. Johnson ◽  
...  
Keyword(s):  
Competitive Ability ◽  
Chenopodium Album ◽  
Protein Abundance ◽  
Crop Species ◽  
Common Lambsquarters ◽  
Treated Leaf ◽  
The Mean ◽  
Shoot Mass ◽  
Sites Of Action

Common lambsquarters tolerance to glyphosate is problematic because of the species' widespread distribution, competitive ability with many crop species, the widespread use of glyphosate in agriculture, and the weed's potential to develop decreased sensitivity to multiple herbicide sites of action. The mechanism that confers common lambsquarters tolerance to glyphosate is not known. Therefore, we conducted experiments to determine the mechanism of tolerance to glyphosate in an accession of common lambsquarters from Indiana relative to a sensitive accession from Wisconsin. The ED50(the effective dose that reduced shoot mass 50% relative to nontreated plants) value for the tolerant accession (1.6 kg ae ha−1± 0.4 standard error of the mean [SEM]) was eightfold greater than the ED50for the sensitive accession (0.2 kg ae ha−1± 0.2 SEM) 28 d after treatment. The glyphosate target-site (EPSPS) DNA sequence at proline 106, shikimate accumulation as an estimate of EPSPS sensitivity, and EPSPS protein abundance did not differ between accessions. Absorption of14C-glyphosate was slightly greater in the tolerant accession than it was in the sensitive accession at 48 and 72 h after treatment (HAT). However, the tolerant accession translocated a smaller percentage of absorbed14C-glyphosate to the tissue above the treated leaf, which included the shoot apical meristem, at 24, 48, and 72 HAT (P ≤ 0.05, 0.01, and 0.10, respectively). These results suggest an important role of reduced translocation in conferring tolerance of common lambsquarters to glyphosate.

scholarly journals Intraoperative neurophysiological mapping and monitoring in spinal tumor surgery: sirens or indispensable tools?

2016 ◽  
Vol 41 (2) ◽  
pp. E18 ◽  
Author(s):  
Antonino Scibilia ◽  
Carmen Terranova ◽  
Vincenzo Rizzo ◽  
Giovanni Raffa ◽  
Adolfo Morelli ◽  
...  
Keyword(s):  
Complex Function ◽  
Spinal Tumor ◽  
Neurological Deficits ◽  
Neurological Injury ◽  
Neurophysiological Monitoring ◽  
Predictive Values ◽  
Effective Role ◽  
Mapping Techniques ◽  
Sensitivity Specificity

Spinal tumor (ST) surgery carries the risk of new neurological deficits in the postoperative period. Intraoperative neurophysiological monitoring and mapping (IONM) represents an effective method of identifying and monitoring in real time the functional integrity of both the spinal cord (SC) and the nerve roots (NRs). Despite consensus favoring the use of IONM in ST surgery, in this era of evidence-based medicine, there is still a need to demonstrate the effective role of IONM in ST surgery in achieving an oncological cure, optimizing patient safety, and considering medicolegal aspects. Thus, neurosurgeons are asked to establish which techniques are considered indispensable. In the present study, the authors focused on the rationale for and the accuracy (sensitivity, specificity, and positive and negative predictive values) of IONM in ST surgery in light of more recent evidence in the literature, with specific emphasis on the role of IONM in reducing the incidence of postoperative neurological deficits. This review confirms the role of IONM as a useful tool in the workup for ST surgery. Individual monitoring and mapping techniques are clearly not sufficient to account for the complex function of the SC and NRs. Conversely, multimodal IONM is highly sensitive and specific for anticipating neurological injury during ST surgery and represents an important tool for preserving neuronal structures and achieving an optimal postoperative functional outcome.

A dynamic process of different helping behavior: from the extended self-theory perspective

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Xi Ouyang ◽  
Kong Zhou ◽  
Yuan-Fang Zhan ◽  
Wen-Jun Yin
Keyword(s):  
Dynamic Process ◽  
Help Seeking ◽  
Task Difficulty ◽  
Helping Behavior ◽  
Mediation Effect ◽  
Extended Self ◽  
Content Type ◽  
Helping Behaviors ◽  
Moderating Role

PurposeDrawing on the extended self-theory, this study explores the dynamic process through which reactive helping could influence proactive helping through self-investment and investigate the moderating role of task difficulty in affecting this process.Design/methodology/approachThis study, with a sample of 582 diary surveys from 66 employees, used experience sampling techniques to analyze the proposed hypotheses.FindingsThe results revealed that self-investment could mediate the positive relationship between reactive helping and proactive helping. Additionally, task difficulty acts as an essential role in facilitating the process raised by reactive helping. Further examination revealed that the moderated mediation effect in this model was also significant.Practical implicationsManagers should encourage help-seeking and positive responses to requests, especially in groups with difficult tasks, which could build helpers’ extended self at work and increase their proactive helping behaviors at the following episode.Originality/valueAs verifying the dynamic trajectory of reactive helping, this study enriches our understanding of whether and how helping behaviors are likely to grow over time. Besides, it complements current pieces of literature by exploring the potential positive implication of reactive helping with a helper-centric perspective.

Differential protein abundance during the first month of regeneration of the Caribbean star coral Montastraea cavernosa

Coral Reefs ◽  
2018 ◽  
Vol 38 (1) ◽  
pp. 45-61 ◽  
Author(s):  
Ryan A. Horricks ◽  
Christophe M. Herbinger ◽  
Brandon N. Lillie ◽  
Paul Taylor ◽  
John S. Lumsden
Keyword(s):  
Protein Abundance ◽  
Differential Protein ◽  
The Caribbean ◽  
Montastraea Cavernosa
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