scholarly journals A Systematic Evaluation of Semispecific Peptide Search Parameter Enables Identification of Previously Undescribed N-Terminal Peptides and Conserved Proteolytic Processing in Cancer Cell Lines

Proteomes ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 26
Author(s):  
Matthias Fahrner ◽  
Lucas Kook ◽  
Klemens Fröhlich ◽  
Martin L. Biniossek ◽  
Oliver Schilling
Keyword(s):  
Open Source ◽  
Cell Lines ◽  
Search Engines ◽  
Mass Spectra ◽  
Proteolytic Processing ◽  
Systematic Evaluation ◽  
Fragment Mass ◽  
The Impact ◽  
Spectrum Matching ◽  
Specific Peptide

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has become the most commonly used technique in explorative proteomic research. A variety of open-source tools for peptide-spectrum matching have become available. Most analyses of explorative MS data are performed using conventional settings, such as fully specific enzymatic constraints. Here we evaluated the impact of the fragment mass tolerance in combination with the enzymatic constraints on the performance of three search engines. Three open-source search engines (Myrimatch, X! Tandem, and MSGF+) were evaluated concerning the suitability in semi- and unspecific searches as well as the importance of accurate fragment mass spectra in non-specific peptide searches. We then performed a semispecific reanalysis of the published NCI-60 deep proteome data applying the most suited parameters. Semi- and unspecific LC-MS/MS data analyses particularly benefit from accurate fragment mass spectra while this effect is less pronounced for conventional, fully specific peptide-spectrum matching. Search speed differed notably between the three search engines for semi- and non-specific peptide-spectrum matching. Semispecific reanalysis of NCI-60 proteome data revealed hundreds of previously undescribed N-terminal peptides, including cases of proteolytic processing or likely alternative translation start sites, some of which were ubiquitously present in all cell lines of the reanalyzed panel. Highly accurate MS2 fragment data in combination with modern open-source search algorithms enable the confident identification of semispecific peptides from large proteomic datasets. The identification of previously undescribed N-terminal peptides in published studies highlights the potential of future reanalysis and data mining in proteomic datasets.

Developer Centrality and the Impact of Value Congruence and Incongruence on Commitment and Code Contribution Activity in Open Source Software Communities

MIS Quarterly ◽  
2019 ◽  
Vol 43 (3) ◽  
pp. 951-976
Author(s):  
Likoebe M. Maruping ◽  
◽  
Sherae L. Daniel ◽  
Marcelo Cataldo ◽  
◽  
...  
Keyword(s):  
Open Source ◽  
Open Source Software ◽  
Value Congruence ◽  
The Impact

scholarly journals PC12 and THP-1 Cell Lines as Neuronal and Microglia Model in Neurobiological Research

2021 ◽  
Vol 11 (9) ◽  
pp. 3729
Author(s):  
Katarzyna Balon ◽  
Benita Wiatrak
Keyword(s):  
Cell Culture ◽  
Dna Damage ◽  
Cell Lines ◽  
Inflammatory Factor ◽  
Research Model ◽  
Differentiated Cells ◽  
Undifferentiated Cells ◽  
Primary Cell Lines ◽  
Neurobiological Research ◽  
The Impact

Models based on cell cultures have become a useful tool in modern scientific research. Since primary cell lines are difficult to obtain and handle, neoplasm-derived lines like PC12 and THP-1 offer a cheap and flexible solution for neurobiological studies but require prior differentiation to serve as a neuronal or microglia model. PC12 cells constitute a suitable research model only after differentiation by incubation with nerve growth factor (NGF) and THP-1 cells after administering a differentiation factor such as phorbol 12-myristate-13-acetate (PMA). Still, quite often, studies are performed on these cancer cells without differentiation. The study aimed to assess the impact of PC12 or THP-1 cell differentiation on sensitivity to harmful factors such as Aβ25-35 (0.001–5 µM) (considered as one of the major detrimental factors in the pathophysiology of Alzheimer’s disease) or lipopolysaccharide (1–100 µM) (LPS; a pro-inflammatory factor of bacterial origin). Results showed that in most of the tests performed, the response of PC12 and THP-1 cells induced to differentiation varied significantly from the effect in undifferentiated cells. In general, differentiated cells showed greater sensitivity to harmful factors in terms of metabolic activity and DNA damage, while in the case of the free radicals, the results were heterogeneous. Obtained data emphasize the importance of proper differentiation of cell lines of neoplastic origin in neurobiological research and standardization of cell culture handling protocols to ensure reliable results.

scholarly journals Impact of RARα and miR-138 on retinoblastoma etoposide resistance

Tumor Biology ◽  
2021 ◽  
Vol 43 (1) ◽  
pp. 11-26
Author(s):  
Maike Busch ◽  
Natalia Miroschnikov ◽  
Jaroslaw Thomas Dankert ◽  
Marc Wiesehöfer ◽  
Klaus Metz ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Lines ◽  
Cancer Progression ◽  
Treated Patient ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Gene Assay ◽  
The Impact

BACKGROUND: Retinoblastoma (RB) is the most common childhood eye cancer. Chemotherapeutic drugs such as etoposide used in RB treatment often cause massive side effects and acquired drug resistances. Dysregulated genes and miRNAs have a large impact on cancer progression and development of chemotherapy resistances. OBJECTIVE: This study was designed to investigate the involvement of retinoic acid receptor alpha (RARα) in RB progression and chemoresistance as well as the impact of miR-138, a potential RARα regulating miRNA. METHODS: RARα and miR-138 expression in etoposide resistant RB cell lines and chemotherapy treated patient tumors compared to non-treated tumors was revealed by Real-Time PCR. Overexpression approaches were performed to analyze the effects of RARα on RB cell viability, apoptosis, proliferation and tumorigenesis. Besides, we addressed the effect of miR-138 overexpression on RB cell chemotherapy resistance. RESULTS: A binding between miR-138 and RARα was shown by dual luciferase reporter gene assay. The study presented revealed that RARα is downregulated in etoposide resistant RB cells, while miR-138 is endogenously upregulated. Opposing RARα and miR-138 expression levels were detectable in chemotherapy pre-treated compared to non-treated RB tumor specimen. Overexpression of RARα increases apoptosis levels and reduces tumor cell growth of aggressive etoposide resistant RB cells in vitro and in vivo. Overexpression of miR-138 in chemo-sensitive RB cell lines partly enhances cell viability after etoposide treatment. CONCLUSIONS: Our findings show that RARα acts as a tumor suppressor in retinoblastoma and is downregulated upon etoposide resistance in RB cells. Thus, RARα may contribute to the development and progression of RB chemo-resistance.

scholarly journals MCR: Open-Source Software to Automate Compilation of Health Study Report-Back

2021 ◽  
Vol 18 (11) ◽  
pp. 6104
Author(s):  
Erin Polka ◽  
Ellen Childs ◽  
Alexa Friedman ◽  
Kathryn S. Tomsho ◽  
Birgit Claus Henn ◽  
...  
Keyword(s):  
Quality Control ◽  
Open Source ◽  
Open Source Software ◽  
Research Team ◽  
Self Determination ◽  
Health Study ◽  
Equitable Access ◽  
Team Members ◽  
Study Participants ◽  
The Impact

Sharing individualized results with health study participants, a practice we and others refer to as “report-back,” ensures participant access to exposure and health information and may promote health equity. However, the practice of report-back and the content shared is often limited by the time-intensive process of personalizing reports. Software tools that automate creation of individualized reports have been built for specific studies, but are largely not open-source or broadly modifiable. We created an open-source and generalizable tool, called the Macro for the Compilation of Report-backs (MCR), to automate compilation of health study reports. We piloted MCR in two environmental exposure studies in Massachusetts, USA, and interviewed research team members (n = 7) about the impact of MCR on the report-back process. Researchers using MCR created more detailed reports than during manual report-back, including more individualized numerical, text, and graphical results. Using MCR, researchers saved time producing draft and final reports. Researchers also reported feeling more creative in the design process and more confident in report-back quality control. While MCR does not expedite the entire report-back process, we hope that this open-source tool reduces the barriers to personalizing health study reports, promotes more equitable access to individualized data, and advances self-determination among participants.

scholarly journals Targeting Immune-Related Molecules in Cancer Therapy: A ComprehensiveIn VitroAnalysis on Patient-Derived Tumor Models

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Claudia Maletzki ◽  
Philine Scheinpflug ◽  
Anika Witt ◽  
Ernst Klar ◽  
Michael Linnebacher
Keyword(s):  
Cell Lines ◽  
Cpg Island ◽  
Molecular Subtype ◽  
Combined Treatment ◽  
Peripheral Blood Lymphocytes ◽  
Molecular Characteristics ◽  
Target Cells ◽  
Selective Treatment ◽  
Cpg Island Methylator Phenotype ◽  
The Impact

This study investigated the impact of immune-related pathway inhibition, among them indolamine 2,3-dioxygenase (IDO), alone and together with immune cells on growth and viability of colorectal cancer (CRC) cells. A panel of patient-derived CRC cell lines with different molecular characteristics (CpG island methylator phenotype, chromosomal, and microsatellite instability) was included. Initial phenotyping of CRC cell lines (n=17) revealed high abundance of immunosuppressive checkpoint-molecules in general, but an individual profile for IDO. Presence of immune-related molecules was independent of the molecular subtype. Selective treatment of CRC cell lines showing high or low IDO expression (n=2 cell lines each) was performed with single agents and combinations of Indoximod, Curcumin, and Gemcitabine with and without the addition of peripheral blood lymphocytes (PBL) in an allogeneic setting. All substances affected CRC cell growth in a cell line specific manner. The combination of Curcumin and Gemcitabine proved to be most effective in tumor cell elimination. Functional read-out analyses identified cellular senescence, after both single and combined treatment. Curcumin alone exerted strong cytotoxic effects by inducing early and late apoptosis. Necrosis was not detectable at all. Addition of lymphocytes generally boosted antitumoral effects of all IDO-inhibitors, with up to 80 % cytotoxicity for the Curcumin treatment. Here, no obvious differences became apparent between individual cell lines. Combined application of Curcumin and low-dose chemotherapy is a promising strategy to kill tumor target cells and to stimulate antitumoral immune responses.

scholarly journals An Efficient Photodynamic Therapy Treatment for Human Pancreatic Adenocarcinoma

2020 ◽  
Vol 9 (1) ◽  
pp. 192 ◽  
Author(s):  
Alexandre Quilbe ◽  
Olivier Moralès ◽  
Martha Baydoun ◽  
Abhishek Kumar ◽  
Rami Mustapha ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Photodynamic Therapy ◽  
Immune System ◽  
Cancer Cells ◽  
Pancreatic Adenocarcinoma ◽  
Cell Lines ◽  
Folate Receptor ◽  
Mice Model ◽  
Gene And Protein Expression ◽  
The Impact

To date, pancreatic adenocarcinoma (ADKP) is a devastating disease for which the incidence rate is close to the mortality rate. The survival rate has evolved only 2–5% in 45 years, highlighting the failure of current therapies. Otherwise, the use of photodynamic therapy (PDT), based on the use of an adapted photosensitizer (PS) has already proved its worth and has prompted a growing interest in the field of oncology. We have developed a new photosensitizer (PS-FOL/PS2), protected by a recently published patent (WO2019 016397-A1, 24 January 2019). This photosensitizer is associated with an addressing molecule (folic acid) targeting the folate receptor 1 (FOLR1) with a high affinity. Folate binds to FOLR1, in a specific way, expressed in 100% of ADKP or over-expressed in 30% of cases. The first objective of this study is to evaluate the effectiveness of this PS2-PDT in four ADKP cell lines: Capan-1, Capan-2, MiapaCa-2, and Panc-1. For this purpose, we first evaluated the gene and protein expression of FOLR1 on four ADKP cell lines. Subsequently, we evaluated PS2’s efficacy in our cell lines and we assessed the impact of PDT on the secretome of cancer cells and its impact on the immune system. Finally, we evaluate the PDT efficacy on a humanized SCID mouse model of pancreatic cancer. In a very interesting way, we observed a significant increase in the proliferation of activated-human PBMC when cultured with conditioned media of ADKP cancer cells subjected to PDT. Furthermore, to evaluate in vivo the impact of this new PS, we analyzed the tumor growth in a humanized SCID mice model of pancreatic cancer. Four conditions were tested: Untreated, mice (nontreated), mice with PS (PS2), mice subjected to illumination (Light only), and mice subjected to illumination in the presence of PS (PDT). We noticed that the mice subjected to PDT presented a strong decrease in the growth of the tumor over time after illumination. Our investigations have not only suggested that PS2-PDT is an effective therapy in the treatment of PDAC but also that it activates the immune system and could be considered as a real adjuvant for anti-cancer vaccination. Thus, this new study provides new treatment options for patients in a therapeutic impasse and will provide a new arsenal in the fight against PDAC.

scholarly journals Google Earth Engine as Multi-Sensor Open-Source Tool for Supporting the Preservation of Archaeological Areas: The Case Study of Flood and Fire Mapping in Metaponto, Italy

Sensors ◽  
2021 ◽  
Vol 21 (5) ◽  
pp. 1791
Author(s):  
Carmen Fattore ◽  
Nicodemo Abate ◽  
Farid Faridani ◽  
Nicola Masini ◽  
Rosa Lasaponara
Keyword(s):  
Open Source ◽  
Archaeological Site ◽  
Unsupervised Classification ◽  
Google Earth ◽  
Heritage Sites ◽  
Cultural Properties ◽  
Google Earth Engine ◽  
Archaeological Areas ◽  
The Impact

In recent years, the impact of Climate change, anthropogenic and natural hazards (such as earthquakes, landslides, floods, tsunamis, fires) has dramatically increased and adversely affected modern and past human buildings including outstanding cultural properties and UNESCO heritage sites. Research about protection/monitoring of cultural heritage is crucial to preserve our cultural properties and (with them also) our history and identity. This paper is focused on the use of the open-source Google Earth Engine tool herein used to analyze flood and fire events which affected the area of Metaponto (southern Italy), near the homonymous Greek-Roman archaeological site. The use of the Google Earth Engine has allowed the supervised and unsupervised classification of areas affected by flooding (2013–2020) and fire (2017) in the past years, obtaining remarkable results and useful information for setting up strategies to mitigate damage and support the preservation of areas and landscape rich in cultural and natural heritage.

scholarly journals Efficacy of an EGFR-Specific Peptide against EGFR-Dependent Cancer Cell Lines and Tumor Xenografts

Neoplasia ◽  
2014 ◽  
Vol 16 (2) ◽  
pp. 105-W2 ◽  
Author(s):  
Aarif Ahsan ◽  
Susmita G. Ramanand ◽  
Ingrid L. Bergin ◽  
Lilli Zhao ◽  
Christopher E. Whitehead ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Tumor Xenografts ◽  
Specific Peptide

scholarly journals Knowledge sharing in open source software communities: motivations and management

2015 ◽  
Vol 19 (4) ◽  
pp. 791-813 ◽  
Author(s):  
Zilia Iskoujina ◽  
Joanne Roberts
Keyword(s):  
Knowledge Sharing ◽  
Open Source ◽  
Open Source Software ◽  
Online Communities ◽  
Descriptive Analysis ◽  
Online Questionnaire ◽  
Content Type ◽  
The Individual ◽  
The Impact

Purpose – This paper aims to add to the understanding of knowledge sharing in online communities through an investigation of the relationship between individual participant’s motivations and management in open source software (OSS) communities. Drawing on a review of literature concerning knowledge sharing in organisations, the factors that motivate participants to share their knowledge in OSS communities, and the management of such communities, it is hypothesised that the quality of management influences the extent to which the motivations of members actually result in knowledge sharing. Design/methodology/approach – To test the hypothesis, quantitative data were collected through an online questionnaire survey of OSS web developers with the aim of gathering respondents’ opinions concerning knowledge sharing, motivations to share knowledge and satisfaction with the management of OSS projects. Factor analysis, descriptive analysis, correlation analysis and regression analysis were used to explore the survey data. Findings – The analysis of the data reveals that the individual participant’s satisfaction with the management of an OSS project is an important factor influencing the extent of their personal contribution to a community. Originality/value – Little attention has been devoted to understanding the impact of management in OSS communities. Focused on OSS developers specialising in web development, the findings of this paper offer an important original contribution to understanding the connections between individual members’ satisfaction with management and their motivations to contribute to an OSS project. The findings reveal that motivations to share knowledge in online communities are influenced by the quality of management. Consequently, the findings suggest that appropriate management can enhance knowledge sharing in OSS projects and online communities, and organisations more generally.

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