Identification of plasma biomarker candidates in glioblastoma using an antibody-array-based proteomic approach

Abstract Background. Glioblastoma multiforme (GBM) is a brain tumour with a very high patient mortality rate, with a median survival of 47 weeks. This might be improved by the identification of novel diagnostic, prognostic and predictive therapy-response biomarkers, preferentially through the monitoring of the patient blood. The aim of this study was to define the impact of GBM in terms of alterations of the plasma protein levels in these patients. Materials and methods. We used a commercially available antibody array that includes 656 antibodies to analyse blood plasma samples from 17 healthy volunteers in comparison with 17 blood plasma samples from patients with GBM. Results. We identified 11 plasma proteins that are statistically most strongly associated with the presence of GBM. These proteins belong to three functional signalling pathways: T-cell signalling and immune responses; cell adhesion and migration; and cell-cycle control and apoptosis. Thus, we can consider this identified set of proteins as potential diagnostic biomarker candidates for GBM. In addition, a set of 16 plasma proteins were significantly associated with the overall survival of these patients with GBM. Guanine nucleotide binding protein alpha (GNAO1) was associated with both GBM presence and survival of patients with GBM. Conclusions. Antibody array analysis represents a useful tool for the screening of plasma samples for potential cancer biomarker candidates in small-scale exploratory experiments; however, clinical validation of these candidates requires their further evaluation in a larger study on an independent cohort of patients.

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Determining Plasma Protein Variation Parameters as a Prerequisite for Biomarker Studies—A TMT-Based LC-MSMS Proteome Investigation

Proteomes ◽

10.3390/proteomes9040047 ◽

2021 ◽

Vol 9 (4) ◽

pp. 47

Author(s):

Lou-Ann C. Andersen ◽

Nicolai Bjødstrup Palstrøm ◽

Axel Diederichsen ◽

Jes Sanddal Lindholt ◽

Lars Melholt Rasmussen ◽

...

Keyword(s):

Sample Size ◽

Plasma Protein ◽

Plasma Proteins ◽

Clinical Chemistry ◽

Biological Variation ◽

Sample Size Determination ◽

Clinical Proteomics ◽

European Federation ◽

Plasma Samples ◽

Proteomic Approach

Specific plasma proteins serve as valuable markers for various diseases and are in many cases routinely measured in clinical laboratories by fully automated systems. For safe diagnostics and monitoring using these markers, it is important to ensure an analytical quality in line with clinical needs. For this purpose, information on the analytical and the biological variation of the measured plasma protein, also in the context of the discovery and validation of novel, disease protein biomarkers, is important, particularly in relation to for sample size calculations in clinical studies. Nevertheless, information on the biological variation of the majority of medium-to-high abundant plasma proteins is largely absent. In this study, we hypothesized that it is possible to generate data on inter-individual biological variation in combination with analytical variation of several hundred abundant plasma proteins, by applying LC-MS/MS in combination with relative quantification using isobaric tagging (10-plex TMT-labeling) to plasma samples. Using this analytical proteomic approach, we analyzed 42 plasma samples prepared in doublets, and estimated the technical, inter-individual biological, and total variation of 265 of the most abundant proteins present in human plasma thereby creating the prerequisites for power analysis and sample size determination in future clinical proteomics studies. Our results demonstrated that only five samples per group may provide sufficient statistical power for most of the analyzed proteins if relative changes in abundances >1.5-fold are expected. Seventeen of the measured proteins are present in the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Biological Variation Database, and demonstrated remarkably similar biological CV’s to the corresponding CV’s listed in the EFLM database suggesting that the generated proteomic determined variation knowledge is useful for large-scale determination of plasma protein variations.

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Proteomic Discovery and Validation of the Confounding Effect of Heparin Administration on the Analysis of Candidate Cardiovascular Biomarkers

Clinical Chemistry ◽

10.1373/clinchem.2017.282665 ◽

2018 ◽

Vol 64 (10) ◽

pp. 1474-1484 ◽

Cited By ~ 8

Author(s):

Hans C Beck ◽

Lisette O Jensen ◽

Charlotte Gils ◽

Albertine M M Ilondo ◽

Martin Frydland ◽

...

Keyword(s):

Myocardial Infarction ◽

Validation Study ◽

Plasma Proteins ◽

Biomarker Discovery ◽

P Value ◽

Plasma Samples ◽

Significance Level ◽

St Segment Elevation ◽

Proteomic Approach ◽

Heparin Administration

Abstract BACKGROUND Several plasma proteins have been suggested as markers for a variety of cardiovascular conditions but fail to qualify in independent patient cohorts. This may relate to interference of medication on plasma protein concentrations. We used proteomics to identify plasma proteins that changed in concentration with heparin administration and therefore potentially may confound their evaluation as biomarkers in situations in which heparin is used. METHODS We used a proteomic approach based on isobaric tagging and nano-LC-MS/MS analysis to quantify several hundred proteins in a discovery study in which individual plasma samples from 9 patients at intravascular ultrasound follow-up 12 months after an acute myocardial infarction before heparin administration and 2, 15, and 60 min after heparin administration; we validated our findings in 500 individual plasma samples obtained at admission from patients with suspected ST segment elevation myocardial infarction (STEMI), of whom 363 were treated with heparin before admission. RESULTS In the discovery study, 25 of 653 identified plasma proteins displayed a changed concentration after heparin administration (Bonferroni-corrected P value at P < 7.66 × 10−5). Fourteen of the proteins changed significantly among heparin-treated patients in the validation study (nominal significance level of P < 6.92 × 10−5). Among heparin-affected proteins in both the discovery study and the validation study were midkine, spondin 1, secreted frizzled-like protein 1, lipoprotein lipase, and follistatin, all previously associated with STEMI. CONCLUSIONS Medications such as heparin administration given before blood sampling may confound biomarker discovery and should be carefully considered in such studies.

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Can Values of Honesty, Hard Work, Loyalty and Discipline Predict Entrepreneurial Orientation of Muslim Owner Managers?

Journal of Emerging Economies and Islamic Research ◽

10.24191/jeeir.v3i1.9049 ◽

2015 ◽

Vol 3 (1) ◽

pp. 31 ◽

Cited By ~ 2

Author(s):

Rohani Mohd ◽

Badrul Hisham Kamaruddin ◽

Khulida Kirana Yahya ◽

Elias Sanidas

Keyword(s):

Entrepreneurial Orientation ◽

Two Dimensions ◽

Hard Work ◽

Small Scale ◽

Sampling Frame ◽

Policy Makers ◽

Learning Institutions ◽

Innovative Orientation ◽

The Impact ◽

True Values

The purpose of the present study is twofold: first, to investigate the true values of Muslim owner managers; second, to examine the impact of these values on entrepreneurial orientations of Muslim small-scale entrepreneurs. 850 Muslim owner managers were selected randomly using the sampling frame provided by MajlisAmanah Rakyat Malaysia (MARA). 162 completed questionnaires were collected and analyzed. For this paper only two dimensions of entrepreneurial orientations were analyzed: proactive orientation and innovative orientation. Interestingly, the findings revealed that Muslim businessmen/women are honest, loyal, disciplined and hard working. Loyalty and honesty are positively related to proactive orientation, while discipline and hard-work are positively related to innovative orientation. The findings provide implications for existing relevant theories, policy makers, practitioners and learning institutions.

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Post-Translational Oxidation Modifications of Blood Plasma Proteins of Cosmonauts after a Long-term Flight: Part I

Human Physiology ◽

10.1134/s0362119720050072 ◽

2020 ◽

Vol 46 (5) ◽

pp. 531-539

Author(s):

I. M. Larina ◽

A. G. Brzhzovsky ◽

A. M. Nosovsky ◽

A. S. Kononikhin ◽

O. I. Orlov

Keyword(s):

Blood Plasma ◽

Plasma Proteins ◽

Blood Plasma Proteins

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Land Subsidence Estimation for Aquifer Drainage Induced by Underground Mining

Energies ◽

10.3390/en14154658 ◽

2021 ◽

Vol 14 (15) ◽

pp. 4658

Author(s):

Artur Guzy ◽

Wojciech T. Witkowski

Keyword(s):

Environmental Impact ◽

Land Subsidence ◽

Field Data ◽

Underground Mining ◽

Small Scale ◽

Aquifer System ◽

Maximum Value ◽

The Impact ◽

Method Model ◽

Impact Of Mining

Land subsidence caused by groundwater withdrawal induced by mining is a relatively unknown phenomenon. This is primarily due to the small scale of such movements compared to the land subsidence caused by deposit extraction. Nonetheless, the environmental impact of drainage-related land subsidence remains underestimated. The research was carried out in the “Bogdanka” coal mine in Poland. First, the historical impact of mining on land subsidence and groundwater head changes was investigated. The outcomes of these studies were used to construct the influence method model. With field data, our model was successfully calibrated and validated. Finally, it was used for land subsidence estimation for 2030. As per the findings, the field of mining exploitation has the greatest land subsidence. In 2014, the maximum value of the phenomenon was 0.313 cm. However, this value will reach 0.364 m by 2030. The spatial extent of land subsidence caused by mining-induced drainage extends up to 20 km beyond the mining area’s boundaries. The presented model provided land subsidence patterns without the need for a complex numerical subsidence model. As a result, the method presented can be effectively used for land subsidence regulation plans considering the impact of mining on the aquifer system.

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Advanced Constitutive Modeling of the Thixotropic Elasto-Visco-Plastic Behavior of Blood: Steady-State Blood Flow in Microtubes

Materials ◽

10.3390/ma14020367 ◽

2021 ◽

Vol 14 (2) ◽

pp. 367

Author(s):

Konstantinos Giannokostas ◽

Yannis Dimakopoulos ◽

Andreas Anayiotos ◽

John Tsamopoulos

Keyword(s):

Blood Flow ◽

Steady State ◽

Constitutive Model ◽

Blood Plasma ◽

Constitutive Modeling ◽

Flow Direction ◽

Momentum Balance ◽

Plastic Behavior ◽

Flow Investigation ◽

The Impact

The present work focuses on the in-silico investigation of the steady-state blood flow in straight microtubes, incorporating advanced constitutive modeling for human blood and blood plasma. The blood constitutive model accounts for the interplay between thixotropy and elasto-visco-plasticity via a scalar variable that describes the level of the local blood structure at any instance. The constitutive model is enhanced by the non-Newtonian modeling of the plasma phase, which features bulk viscoelasticity. Incorporating microcirculation phenomena such as the cell-free layer (CFL) formation or the Fåhraeus and the Fåhraeus-Lindqvist effects is an indispensable part of the blood flow investigation. The coupling between them and the momentum balance is achieved through correlations based on experimental observations. Notably, we propose a new simplified form for the dependence of the apparent viscosity on the hematocrit that predicts the CFL thickness correctly. Our investigation focuses on the impact of the microtube diameter and the pressure-gradient on velocity profiles, normal and shear viscoelastic stresses, and thixotropic properties. We demonstrate the microstructural configuration of blood in steady-state conditions, revealing that blood is highly aggregated in narrow tubes, promoting a flat velocity profile. Additionally, the proper accounting of the CFL thickness shows that for narrow microtubes, the reduction of discharged hematocrit is significant, which in some cases is up to 70%. At high pressure-gradients, the plasmatic proteins in both regions are extended in the flow direction, developing large axial normal stresses, which are more significant in the core region. We also provide normal stress predictions at both the blood/plasma interface (INS) and the tube wall (WNS), which are difficult to measure experimentally. Both decrease with the tube radius; however, they exhibit significant differences in magnitude and type of variation. INS varies linearly from 4.5 to 2 Pa, while WNS exhibits an exponential decrease taking values from 50 mPa to zero.

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Foreign investment in emerging legal medicinal cannabis markets: the Jamaica case study

Globalization and Health ◽

10.1186/s12992-021-00687-3 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Marta Rychert ◽

Machel Anthony Emanuel ◽

Chris Wilkins

Keyword(s):

Civil Society ◽

Foreign Investment ◽

Production Efficiency ◽

Production Quality ◽

Small Scale ◽

Organic Cultivation ◽

Enhanced Production ◽

Political Interference ◽

Medicinal Cannabis ◽

The Impact

Abstract Introduction The establishment of a legal market for medicinal cannabis under the Dangerous Drugs Amendment Act 2015 has positioned Jamaica at the forefront of cannabis law reform in the developing world. Many local cannabis businesses have attracted investment from overseas, including from Canada, US and Europe. Aim To explore the opportunities and risks of foreign investment in an emerging domestic legal cannabis market in a developing country. Methods Thematic analysis of semi-structured face-to-face interviews with 22 key informants (KIs) from the Jamaican government, local cannabis industry, academia and civil society, and field observations of legal and illegal cannabis cultivators. Results KIs from the Jamaican public agencies and domestic cannabis entrepreneurs saw foreign investment as an essential source of capital to finance the start-up costs of legal cannabis businesses. Local cannabis entrepreneurs prioritised investors with the greatest financial resources, brand reputation and export networks. They also considered how allied an investor was with their business vision (e.g., organic cultivation, medical vs. recreational). The key benefits of partnering with a foreign investor included transfer of technical knowledge and financial capital, which enhanced production, quality assurance and seed-to-sale tracking. Some KIs expressed concern over investors’ focus on increasing production efficiency and scale at the expense of funding research and development (R&D) and clinical trials. KIs from the local industry, government agencies and civil society highlighted the risks of ‘predatory’ shareholder agreements and domestic political interference. Concerns were raised about the impact of foreign investment on the diversity of the domestic cannabis sector in Jamaica, including the commitment to transition traditional illegal small-scale cannabis cultivators to the legal sector. Conclusion While foreign investment has facilitated the commercialisation of the cannabis sector in Jamaica, regulatory measures are also needed to protect the domestic industry and support the transition of small-scale illegal cultivators to the legal regime. Foreign investments may alter the economic, social and political determinants of health in transitioning from illegal to legal cannabis market economy.

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BIOPHYSICAL STUDIES OF BLOOD PLASMA PROTEINS

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)41202-6 ◽

1946 ◽

Vol 165 (1) ◽

pp. 21-35 ◽

Cited By ~ 8

Author(s):

H.F. Deutsch ◽

R.A. Alberty ◽

L.J. Gosting

Keyword(s):

Blood Plasma ◽

Plasma Proteins ◽

Biophysical Studies ◽

Blood Plasma Proteins

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A Model-Based Tool for Assessing the Impact of Land Use Change Scenarios on Flood Risk in Small-Scale River Systems—Part 1: Pre-Processing of Scenario Based Flood Characteristics for the Current State of Land Use

Hydrology ◽

10.3390/hydrology8030102 ◽

2021 ◽

Vol 8 (3) ◽

pp. 102

Author(s):

Frauke Kachholz ◽

Jens Tränckner

Keyword(s):

Land Use ◽

River Flow ◽

Land Use Changes ◽

Small Rivers ◽

Small Scale ◽

Model Parameters ◽

Ungauged Catchments ◽

Model Based ◽

Current State ◽

The Impact

Land use changes influence the water balance and often increase surface runoff. The resulting impacts on river flow, water level, and flood should be identified beforehand in the phase of spatial planning. In two consecutive papers, we develop a model-based decision support system for quantifying the hydrological and stream hydraulic impacts of land use changes. Part 1 presents the semi-automatic set-up of physically based hydrological and hydraulic models on the basis of geodata analysis for the current state. Appropriate hydrological model parameters for ungauged catchments are derived by a transfer from a calibrated model. In the regarded lowland river basins, parameters of surface and groundwater inflow turned out to be particularly important. While the calibration delivers very good to good model results for flow (Evol =2.4%, R = 0.84, NSE = 0.84), the model performance is good to satisfactory (Evol = −9.6%, R = 0.88, NSE = 0.59) in a different river system parametrized with the transfer procedure. After transferring the concept to a larger area with various small rivers, the current state is analyzed by running simulations based on statistical rainfall scenarios. Results include watercourse section-specific capacities and excess volumes in case of flooding. The developed approach can relatively quickly generate physically reliable and spatially high-resolution results. Part 2 builds on the data generated in part 1 and presents the subsequent approach to assess hydrologic/hydrodynamic impacts of potential land use changes.

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Whole-genome sequencing from the New Zealand Saccharomyces cerevisiae population reveals the genomic impacts of novel microbial range expansion

G3 Genes|Genome|Genetics ◽

10.1093/g3journal/jkaa027 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Peter Higgins ◽

Cooper A Grace ◽

Soon A Lee ◽

Matthew R Goddard

Keyword(s):

Saccharomyces Cerevisiae ◽

New Zealand ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Range Expansion ◽

Copy Number ◽

Small Scale ◽

Whole Genome ◽

Copy Number Changes ◽

The Impact

Abstract Saccharomyces cerevisiae is extensively utilized for commercial fermentation, and is also an important biological model; however, its ecology has only recently begun to be understood. Through the use of whole-genome sequencing, the species has been characterized into a number of distinct subpopulations, defined by geographical ranges and industrial uses. Here, the whole-genome sequences of 104 New Zealand (NZ) S. cerevisiae strains, including 52 novel genomes, are analyzed alongside 450 published sequences derived from various global locations. The impact of S. cerevisiae novel range expansion into NZ was investigated and these analyses reveal the positioning of NZ strains as a subgroup to the predominantly European/wine clade. A number of genomic differences with the European group correlate with range expansion into NZ, including 18 highly enriched single-nucleotide polymorphism (SNPs) and novel Ty1/2 insertions. While it is not possible to categorically determine if any genetic differences are due to stochastic process or the operations of natural selection, we suggest that the observation of NZ-specific copy number increases of four sugar transporter genes in the HXT family may reasonably represent an adaptation in the NZ S. cerevisiae subpopulation, and this correlates with the observations of copy number changes during adaptation in small-scale experimental evolution studies.

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