Subjects -> BIOLOGY (Total: 3174 journals)
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BIOLOGY (1491 journals)            First | 1 2 3 4 5 6 7 8 | Last

Showing 201 - 400 of 1720 Journals sorted alphabetically
Biological Research     Open Access   (Followers: 1)
Biological Rhythm Research     Hybrid Journal   (Followers: 1)
Biological Theory     Hybrid Journal   (Followers: 3)
Biological Trace Element Research     Hybrid Journal  
Biologicals     Full-text available via subscription   (Followers: 7)
Biologics: Targets & Therapy     Open Access   (Followers: 1)
Biologie Aujourd'hui     Full-text available via subscription  
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 36)
Biologija     Open Access  
Biology     Open Access   (Followers: 3)
Biology and Philosophy     Hybrid Journal   (Followers: 18)
Biology Bulletin     Hybrid Journal   (Followers: 1)
Biology Bulletin Reviews     Hybrid Journal  
Biology Direct     Open Access   (Followers: 9)
Biology Letters     Full-text available via subscription   (Followers: 44)
Biology Methods and Protocols     Open Access  
Biology of Sex Differences     Open Access   (Followers: 1)
Biology of the Cell     Full-text available via subscription   (Followers: 9)
Biology Open     Open Access  
Biology, Medicine, & Natural Product Chemistry     Open Access   (Followers: 2)
Bioma : Jurnal Ilmiah Biologi     Open Access  
Biomacromolecules     Hybrid Journal   (Followers: 23)
Biomarker Insights     Open Access   (Followers: 2)
Biomarkers     Hybrid Journal   (Followers: 4)
Biomass and Bioenergy     Partially Free   (Followers: 8)
Biomaterials     Hybrid Journal   (Followers: 55)
Biomaterials Advances     Full-text available via subscription   (Followers: 19)
Biomath     Open Access  
Biomatter     Open Access  
Biomechanics and Modeling in Mechanobiology     Hybrid Journal   (Followers: 8)
Biomedical Chromatography     Hybrid Journal   (Followers: 6)
Biomedical Engineering     Hybrid Journal   (Followers: 11)
Biomedical Engineering and Computational Biology     Open Access   (Followers: 11)
BioMedical Engineering OnLine     Open Access   (Followers: 4)
Biomedical Engineering: Applications, Basis and Communications     Hybrid Journal   (Followers: 4)
Biomedical Journal     Open Access   (Followers: 5)
Biomedical Science and Engineering     Open Access   (Followers: 5)
Biomedical Signal Processing and Control     Hybrid Journal   (Followers: 9)
BioMetals     Hybrid Journal   (Followers: 1)
Biometrical Letters     Open Access  
Biometrics     Hybrid Journal   (Followers: 51)
Biometrika     Hybrid Journal   (Followers: 21)
Biomimetic Intelligence and Robotics     Open Access  
Biomolecular NMR Assignments     Hybrid Journal   (Followers: 3)
Biomolecules     Open Access   (Followers: 1)
BioNanoScience     Partially Free   (Followers: 3)
Bionature     Open Access   (Followers: 1)
Biopreservation and Biobanking     Hybrid Journal   (Followers: 2)
Bioprocess and Biosystems Engineering     Hybrid Journal   (Followers: 9)
Bioresource Technology     Partially Free   (Followers: 9)
BioRisk     Open Access   (Followers: 2)
Biosaintifika : Journal of Biology & Biology Education     Open Access  
BioScience     Hybrid Journal   (Followers: 27)
Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science     Hybrid Journal   (Followers: 3)
Biosemiotics     Hybrid Journal   (Followers: 1)
Biosensors     Open Access   (Followers: 3)
Biosensors and Bioelectronics     Hybrid Journal   (Followers: 27)
Biosensors and Bioelectronics : X     Open Access   (Followers: 2)
Bioseparation     Hybrid Journal   (Followers: 1)
Biosfer : Jurnal Biologi dan Pendidikan Biologi     Open Access  
Biosfer : Jurnal Tadris Biologi     Open Access  
BioSocieties     Hybrid Journal   (Followers: 3)
Biospecies     Open Access  
BIOspektrum     Hybrid Journal   (Followers: 5)
Biostatistics     Hybrid Journal   (Followers: 18)
Biosystematics and Ecology     Open Access   (Followers: 3)
Biosystems     Hybrid Journal   (Followers: 3)
Biosystems Diversity     Open Access  
Biota Amazônia     Open Access  
Biota Neotropica     Open Access  
Biotechnology Advances     Hybrid Journal   (Followers: 34)
Biotropia : The Southeast Asian Journal of Tropical Biology     Open Access  
Biotropica     Hybrid Journal   (Followers: 19)
Birth Defects Research     Hybrid Journal  
BJHM Open Research     Full-text available via subscription   (Followers: 1)
BMC Bioinformatics     Open Access   (Followers: 110)
BMC Biology     Open Access   (Followers: 50)
BMC Developmental Biology     Open Access   (Followers: 13)
BMC Evolutionary Biology     Open Access   (Followers: 58)
BMC Genomics     Open Access   (Followers: 69)
BMC Molecular and Cell Biology     Open Access   (Followers: 40)
BMC Proceedings     Full-text available via subscription   (Followers: 2)
BMC Research Notes     Open Access   (Followers: 3)
BMC Structural Biology     Open Access   (Followers: 8)
BMC Systems Biology     Open Access   (Followers: 16)
Boletín Científico : Centro de Museos. Museo de Historia Natural     Open Access  
Boletín del Centro de Investigaciones Biológicas     Open Access  
Boletín Micológico     Open Access  
Bone Reports     Open Access  
Bonorowo Wetlands     Open Access  
Borneo Journal of Resource Science and Technology     Open Access  
Bothalia : African Biodiversity & Conservation     Open Access  
Brain Science Advances     Open Access  
Brazilian Journal of Biological Sciences     Open Access  
Breastfeeding Medicine     Hybrid Journal   (Followers: 20)
Briefings in Bioinformatics     Hybrid Journal   (Followers: 43)
Briefings in Functional Genomics     Hybrid Journal   (Followers: 3)
British Poultry Abstracts     Hybrid Journal   (Followers: 3)
Brittonia     Hybrid Journal  
Bulletin de la Société Royale des Sciences de Liège     Open Access  
Bulletin of Experimental Biology and Medicine     Hybrid Journal  
Bulletin of Mathematical Biology     Hybrid Journal   (Followers: 9)
Bulletin of the Ecological Society of America     Open Access   (Followers: 4)
Bulletin of the Lebedev Physics Institute     Hybrid Journal  
Butlletí de la Institució Catalana d'Història Natural     Open Access  
CABI Agriculture and Bioscience     Open Access   (Followers: 1)
Caldasia     Open Access  
Cameroon Journal of Experimental Biology     Open Access  
Canadian Journal of Bioethics     Open Access  
Canadian Journal of Plant Pathology     Hybrid Journal   (Followers: 3)
Çanakkale Onsekiz Mart University Journal of Marine Sciences and Fisheries     Open Access  
Cancer Biology & Therapy     Open Access   (Followers: 11)
Cancer Cell International     Open Access   (Followers: 7)
Carbon Capture Science & Technology     Open Access  
Carbon Management     Hybrid Journal   (Followers: 5)
Carbon Resources Conversion     Open Access   (Followers: 2)
Caryologia : International Journal of Cytology, Cytosystematics and Cytogenetics     Partially Free  
Caucasiana     Open Access  
Cell     Full-text available via subscription   (Followers: 1145)
Cell Adhesion & Migration     Open Access   (Followers: 9)
Cell and Tissue Banking     Hybrid Journal   (Followers: 1)
Cell and Tissue Biology     Hybrid Journal   (Followers: 4)
Cell and Tissue Research     Hybrid Journal   (Followers: 5)
Cell Biochemistry and Function     Hybrid Journal   (Followers: 8)
Cell Biology and Development     Open Access   (Followers: 2)
Cell Biology and Toxicology     Hybrid Journal   (Followers: 10)
Cell Biology Education     Free   (Followers: 4)
Cell Biology International     Hybrid Journal   (Followers: 4)
Cell Biology International Reports     Hybrid Journal   (Followers: 2)
Cell Calcium     Hybrid Journal   (Followers: 2)
Cell Communication & Adhesion     Hybrid Journal   (Followers: 2)
Cell Cycle     Full-text available via subscription   (Followers: 5)
Cell Death and Differentiation     Hybrid Journal   (Followers: 7)
Cell Discovery     Open Access   (Followers: 2)
Cell Division     Open Access   (Followers: 1)
Cell Genomics     Full-text available via subscription   (Followers: 2)
Cell Metabolism     Full-text available via subscription   (Followers: 58)
Cell Proliferation     Open Access  
Cell Reports     Open Access   (Followers: 61)
Cell Reports Medicine     Open Access   (Followers: 3)
Cell Reports Methods     Open Access   (Followers: 1)
Cell Research     Hybrid Journal   (Followers: 11)
Cell Stress and Chaperones     Hybrid Journal   (Followers: 1)
Cell Surface     Open Access  
Cell Systems     Hybrid Journal   (Followers: 7)
Cells     Open Access   (Followers: 2)
Cells & Development     Hybrid Journal   (Followers: 3)
Cells Tissues Organs     Full-text available via subscription   (Followers: 1)
Cellular Immunology     Hybrid Journal   (Followers: 29)
Cellular Logistics     Full-text available via subscription  
Cellular Microbiology     Hybrid Journal   (Followers: 12)
Cellular Oncology     Hybrid Journal   (Followers: 3)
Cellular Reprogramming     Hybrid Journal  
Cellular Signalling     Hybrid Journal   (Followers: 10)
Ceylon Journal of Science     Open Access  
Channels     Open Access   (Followers: 1)
Check List : The Journal of Biodiversity Data     Open Access   (Followers: 2)
Chem     Hybrid Journal  
ChemBioEng Reviews     Full-text available via subscription   (Followers: 3)
Chemosensory Perception     Hybrid Journal  
Chirality     Hybrid Journal  
Chromosoma     Hybrid Journal  
Chromosome Research     Hybrid Journal   (Followers: 2)
Ciencia     Open Access  
Ciencia Amazónica (Iquitos)     Open Access  
Ciência ET Praxis     Open Access  
CienciaUAT     Open Access  
Cladistics     Hybrid Journal   (Followers: 7)
Climate Change Ecology     Open Access   (Followers: 15)
Clinical Dysmorphology     Hybrid Journal  
Clinical Phytoscience     Open Access  
Clinical Proteomics     Open Access   (Followers: 3)
Clinical Spectroscopy     Open Access   (Followers: 1)
Coevolution     Open Access  
Cogent Biology     Open Access  
Cognitive Neurodynamics     Hybrid Journal   (Followers: 2)
Cold Spring Harbor Perspectives in Biology     Full-text available via subscription   (Followers: 3)
Cold Spring Harbor Protocols     Full-text available via subscription   (Followers: 4)
Communication in Biomathematical Sciences     Open Access   (Followers: 2)
Communications Biology     Open Access  
Communications in Applied Sciences     Open Access  
Communications Materials     Open Access  
Communicative & Integrative Biology     Open Access  
Community Ecology     Full-text available via subscription   (Followers: 27)
Comparative Medicine     Full-text available via subscription   (Followers: 5)
Composite Interfaces     Hybrid Journal   (Followers: 6)
Comptes Rendus : Chimie     Open Access  
Comptes Rendus Biologies     Open Access   (Followers: 1)
Computational Biology Journal     Open Access   (Followers: 6)
Computational Mathematics and Mathematical Physics     Hybrid Journal   (Followers: 5)
Computer Methods in Biomechanics and Biomedical Engineering     Hybrid Journal   (Followers: 10)
Computer Methods in Biomechanics and Biomedical Engineering : Imaging & Visualization     Hybrid Journal  
Computers in Biology and Medicine     Hybrid Journal   (Followers: 11)
Connective Tissue Research     Hybrid Journal  
Contact (CTC)     Open Access  
Contributions to Plasma Physics     Hybrid Journal   (Followers: 3)
CRISPR Journal     Hybrid Journal  
Critical Reviews in Clinical Laboratory Sciences     Hybrid Journal   (Followers: 19)
Crustaceana     Hybrid Journal   (Followers: 6)
Cryobiology     Hybrid Journal   (Followers: 3)

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Similar Journals
Journal Cover
Clinical Proteomics
Journal Prestige (SJR): 1.443
Citation Impact (citeScore): 4
Number of Followers: 3  

  This is an Open Access Journal Open Access journal
ISSN (Print) 1559-0275 - ISSN (Online) 1542-6416
Published by Springer-Verlag Homepage  [2469 journals]
  • 13C15N: glucagon-based novel isotope dilution mass spectrometry method for
           measurement of glucagon metabolism in humans

    • Abstract: Background Glucagon serves as an important regulatory hormone for regulating blood glucose concentration with tight feedback control exerted by insulin and glucose. There are critical gaps in our understanding of glucagon kinetics, pancreatic α cell function and intra-islet feedback network that are disrupted in type 1 diabetes. This is important for translational research applications of evolving dual-hormone (insulin + glucagon) closed-loop artificial pancreas algorithms and their usage in type 1 diabetes. Thus, it is important to accurately measure glucagon kinetics in vivo and to develop robust models of glucose-insulin-glucagon interplay that could inform next generation of artificial pancreas algorithms. Methods Here, we describe the administration of novel 13C15N heavy isotope-containing glucagon tracers—FF glucagon [(Phe 6 13C9,15N; Phe 22 13C9,15N)] and FFLA glucagon [(Phe 6 13C9,15N; Phe 22 13C9,15N; Leu 14 13C6,15N; Ala 19 13C3)] followed by anti-glucagon antibody-based enrichment and LC–MS/MS based-targeted assays using high-resolution mass spectrometry to determine levels of infused glucagon in plasma samples. The optimized assay results were applied for measurement of glucagon turnover in subjects with and without type 1 diabetes infused with isotopically labeled glucagon tracers. Results The limit of quantitation was found to be 1.56 pg/ml using stable isotope-labeled glucagon as an internal standard. Intra and inter-assay variability was < 6% and < 16%, respectively, for FF glucagon while it was < 5% and < 23%, respectively, for FFLA glucagon. Further, we carried out a novel isotope dilution technique using glucagon tracers for studying glucagon kinetics in type 1 diabetes. Conclusions The methods described in this study for simultaneous detection and quantitation of glucagon tracers have clinical utility for investigating glucagon kinetics in vivo in humans.
      PubDate: 2022-05-19
       
  • Airway fibrin formation cascade in allergic asthma exacerbation:
           implications for inflammation and remodeling

    • Abstract: Background Airway remodeling in patients with asthma, which leads to a decline in pulmonary function, is likely the result of repeated exacerbations often provoked by aeroallergen exposures. Aeroallegen exposure triggers a stereotypic response orchestrated by growth factor cytokines and other protein mediators. This results in a late-phase allergic reaction characterized by vascular permeability, recruitment of activated leukocytes, and activation of structural cells of the airway. The spectrum of protein mediators and their functions are incompletely understood. Methods Bronchoalveolar lavage fluid (BALF) samples were obtained from 12 volunteers who exhibited robust eosinophilic recruitment following segmental bronchial provocation with allergen (SBP-Ag). We systematically identified and quantified proteins in BALF using high-performance liquid chromatography–high-resolution mass spectrometry (LC–MS/MS) followed by pathway analysis and correlations with airway physiology. Results Pairwise analysis of protein abundance in BALF pre- vs post-SBP-Ag revealed that 55 proteins were upregulated and 103 proteins were downregulated. We observed enrichment of groups of proteins mapping to hemostasis/fibrin clot, platelet activation, lipoprotein assembly, neutrophil degranulation proteins, and acute-phase inflammation-airway remodeling pathways. The abundances of F2 and Fibrinogen γ (FGG) correlated with eosinophil numbers, whereas SERPINA3 negatively correlated with change in FeNO. The coagulation proteins F2 and KNG negatively correlated with FN1 an index of airway remodeling. Interestingly, patients with lower FEV1 showed distinct allergen-induced patterns of 8 BALF proteins, including MUC1, alarmins (HSPB1), and actin polymerization factors. Conclusions Protein abundance of the fibrin formation cascade, platelet activation and remodeling are associated with late-phase leukocyte numbers and markers of remodeling. Patients with lower FEV1 have distinct dynamic responses to allergen.
      PubDate: 2022-05-19
       
  • Maternal serum CFHR4 protein as a potential non-invasive marker of
           ventricular septal defects in offspring: evidence from a comparative
           proteomics study

    • Abstract: Background Despite advances in diagnosis of congenital heart defects, there is no non-invasive biomarker clinically available for the early detection of fetal ventricular septal defects (VSD). Methods This study was to profile differentially expressed proteins (DEP) in the first trimester maternal plasma samples that were collected in the 12th–14th week of gestation and identify potential biomarkers for VSD. Maternal plasma samples of ten case–control pairs of women (who had given birth to an isolated VSD infant or not) were selected from a birth cohort biospecimen bank for identifying DEPs by using high-performance liquid chromatography-tandem mass spectrometry-based comparative proteomics. Results There were 35 proteins with significantly different levels between cases and controls, including 9 upregulated and 26 downregulated proteins. With Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and protein–protein interaction analyses, most of the DEPs were clustered in pathways related to B cell-mediated immune responses, complement activation, and phagocytosis. Three DEPs were validated using enzyme-linked immunosorbent assay in another set of samples consisting of 31 cases and 33 controls. And CFHR4, a key regulator in complement cascades, was found to be significantly upregulated in cases as compared to controls. Conclusions Subsequent logistic regression and receiver operating characteristic analysis suggested maternal serum CFHR4 as a promising biomarker of fetal VSD. Further studies are warranted to verify the findings.
      PubDate: 2022-05-19
       
  • Label-free LC–MS/MS proteomics analyses reveal proteomic changes in
           oxidative stress and the SOD antioxidant strategy in TM cells

    • Abstract: Background Treatment for glaucoma has traditionally been limited to reducing intraocular pressure (IOP). Inhibiting oxidative stress in the trabecular meshwork (TM) is regarded as a new treatment for glaucoma; however, the effects do not meet expectations. Exploring the mechanism by which oxidative stress and antioxidant stress occur in TM cells will offer clues to aid the development of new treatments. Methods and results In our study, we cultured TM cells and used H2O2 and SOD to induce and inhibit oxidative stress, respectively. Label-free LC–MS/MS quantitative proteomic analysis was conducted to analyze the differentially expressed proteins and relevant signaling pathways. A total of 24 upregulated proteins and 18 downregulated proteins were identified under oxidative stress. PTGS2, TGFβr2 and ICAM-1 are the key proteins. The PTGS2/NF-ĸb pathway, TGF-β/Smad signaling pathway and AGE-RAGE signaling pathway in diabetic complications may be the major signaling pathways under conditions of ROS-induced damage in TM cells. Seventy-eight proteins were upregulated and 73 proteins were downregulated under antioxidant stress in TM cells. The key protein was ICAM-1, which participates in the African trypanosomiasis pathway, one of the most important pathways under antioxidant stress. Combining the results of the Venn diagram with protein–protein interactions (PPIs), ICAM-1 was identified as the major protein. Cell Counting Kit-8 (CCK-8) and western blotting (WB) were used to reveal that suppressing the expression of ICAM-1 would improve the survival of TM cells. Conclusions Key proteins and signaling pathways play important roles in the mechanisms of oxidative stress and antioxidant strategies in TM cells. ICAM-1 knockdown can suppress the apoptosis of TM cells induced by H2O2, which may reveal new therapeutic targets and biomarkers for glaucoma.
      PubDate: 2022-05-14
       
  • Optimized sample preparation and data analysis for TMT proteomic analysis
           of cerebrospinal fluid applied to the identification of Alzheimer’s
           disease biomarkers

    • Abstract: Background Cerebrospinal fluid (CSF) is an important biofluid for biomarkers of neurodegenerative diseases such as Alzheimer’s disease (AD). By employing tandem mass tag (TMT) proteomics, thousands of proteins can be quantified simultaneously in large cohorts, making it a powerful tool for biomarker discovery. However, TMT proteomics in CSF is associated with analytical challenges regarding sample preparation and data processing. In this study we address those challenges ranging from data normalization over sample preparation to sample analysis. Method Using liquid chromatography coupled to mass-spectrometry (LC–MS), we analyzed TMT multiplex samples consisting of either identical or individual CSF samples, evaluated quantification accuracy and tested the performance of different data normalization approaches. We examined MS2 and MS3 acquisition strategies regarding accuracy of quantification and performed a comparative evaluation of filter-assisted sample preparation (FASP) and an in-solution protocol. Finally, four normalization approaches (median, quantile, Total Peptide Amount, TAMPOR) were applied to the previously published European Medical Information Framework Alzheimer’s Disease Multimodal Biomarker Discovery (EMIF-AD MBD) dataset. Results The correlation of measured TMT reporter ratios with spiked-in standard peptide amounts was significantly lower for TMT multiplexes composed of individual CSF samples compared with those composed of aliquots of a single CSF pool, demonstrating that the heterogeneous CSF sample composition influences TMT quantitation. Comparison of TMT reporter normalization methods showed that the correlation could be improved by applying median- and quantile-based normalization. The slope was improved by acquiring data in MS3 mode, albeit at the expense of a 29% decrease in the number of identified proteins. FASP and in-solution sample preparation of CSF samples showed a 73% overlap in identified proteins. Finally, using optimized data normalization, we present a list of 64 biomarker candidates (clinical AD vs. controls, p < 0.01) identified in the EMIF-AD cohort. Conclusion We have evaluated several analytical aspects of TMT proteomics in CSF. The results of our study provide practical guidelines to improve the accuracy of quantification and aid in the design of sample preparation and analytical protocol. The AD biomarker list extracted from the EMIF-AD cohort can provide a valuable basis for future biomarker studies and help elucidate pathogenic mechanisms in AD.
      PubDate: 2022-05-14
       
  • Transcriptome profiling and proteomic validation reveals targets of the
           androgen receptor signaling in the BT-474 breast cancer cell line

    • Abstract: Background Accumulating evidence suggests that the androgen receptor (AR) and its endogenous ligands influence disease progression in breast cancer (BCa). However, AR-mediated changes in BCa differ among the various BCa subtypes according to their hormone receptor profile [i.e., presence/absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2, (HER2)]. Thus, we explored the androgen-regulated transcriptomic changes in the ER+PR+HER2+ BCa cell line, BT-474, and compared them with PR-mediated changes. Methods We performed RNA sequencing analysis in treated BT-474 cells with dihydrotestosterone (DHT) and progesterone. Validation of the top ten differentially androgen-regulated genes and a number of other genes found in enriched signaling pathways was performed by qRT-PCR in BT-474 and other BCa cell lines. In addition, a parallel reaction monitoring targeted proteomic approach was developed to verify selected transcripts at the protein level. Results In total 19,450 transcripts were detected, of which 224 were differentially regulated after DHT treatment. The increased expression of two well-known androgen-regulated genes, KLK2 (p < 0.05) and KLK3 (p < 0.001), confirmed the successful androgen stimulation in BT-474 cells. The transcription factor, ZBTB16, was the most highly upregulated gene, with ~ 1000-fold change (p < 0.001). Pathway enrichment analysis revealed downregulation of the DNA replication processes (p < 0.05) and upregulation of the androgen signaling and fatty acid metabolism pathways (p < 0.05). Changes related to progesterone treatment showed opposite effects in gene expression than DHT treatment. Similar expression profiles were observed among other BCa cell lines expressing high levels of AR (ZR75.1 and MBA-MB-453). The parallel reaction monitoring targeted proteomic analysis further confirmed that altered protein expression (KLK3, ALOX15B) in the supernatant and cell lysate of DHT-treated BT-474 cells, compared to control cells. Discussion Our findings suggest that AR modulates the metabolism of BT-474 cells by affecting the expression of a large number of genes and proteins. Based on further pathway analysis, we suggest that androgen receptor acts as a tumor suppressor in the BT-474 cells.
      PubDate: 2022-05-14
       
  • Correction: A SISCAPA-based approach for detection of SARS-CoV-2 viral
           antigens from clinical samples

    • PubDate: 2022-05-04
       
  • Systematic evaluation and optimization of protein extraction parameters in
           diagnostic FFPE specimens

    • Abstract: Objectives Formalin-fixed paraffin-embedded (FFPE) tissue is the standard material for diagnostic pathology but poses relevant hurdles to accurate protein extraction due to cross-linking and chemical alterations. While numerous extraction protocols and chemicals have been described, systematic comparative analyses are limited. Various parameters were thus investigated in their qualitative and quantitative effects on protein extraction (PE) efficacy. Special emphasis was put on preservation of membrane proteins (MP) as key subgroup of functionally relevant proteins. Methods Using the example of urothelial carcinoma, FFPE tissue sections were subjected to various deparaffinization, protein extraction and antigen retrieval protocols and buffers as well as different extraction techniques. Performance was measured by protein concentration and western blot analysis of cellular compartment markers as well as liquid chromatography-coupled mass spectrometry (LC–MS). Results Commercially available extraction buffers showed reduced extraction of MPs and came at considerably increased costs. On-slide extraction did not improve PE whereas several other preanalytical steps could be simplified. Systematic variation of temperature and exposure duration demonstrated a quantitatively relevant corridor of optimal antigen retrieval. Conclusions Preanalytical protein extraction can be optimized at various levels to improve unbiased protein extraction and to reduce time and costs.
      PubDate: 2022-05-02
       
  • Use of MS-GUIDE for identification of protein biomarkers for risk
           stratification of patients with prostate cancer

    • Abstract: Background Non-invasive liquid biopsies could complement current pathological nomograms for risk stratification of prostate cancer patients. Development and testing of potential liquid biopsy markers is time, resource, and cost-intensive. For most protein targets, no antibodies or ELISAs for efficient clinical cohort pre-evaluation are currently available. We reasoned that mass spectrometry-based prescreening would enable the cost-effective and rational preselection of candidates for subsequent clinical-grade ELISA development. Methods Using Mass Spectrometry-GUided Immunoassay DEvelopment (MS-GUIDE), we screened 48 literature-derived biomarker candidates for their potential utility in risk stratification scoring of prostate cancer patients. Parallel reaction monitoring was used to evaluate these 48 potential protein markers in a highly multiplexed fashion in a medium-sized patient cohort of 78 patients with ground-truth prostatectomy and clinical follow-up information. Clinical-grade ELISAs were then developed for two of these candidate proteins and used for significance testing in a larger, independent patient cohort of 263 patients. Results Machine learning-based analysis of the parallel reaction monitoring data of the liquid biopsies prequalified fibronectin and vitronectin as candidate biomarkers. We evaluated their predictive value for prostate cancer biochemical recurrence scoring in an independent validation cohort of 263 prostate cancer patients using clinical-grade ELISAs. The results of our prostate cancer risk stratification test were statistically significantly 10% better than results of the current gold standards PSA alone, PSA plus prostatectomy biopsy Gleason score, or the National Comprehensive Cancer Network score in prediction of recurrence. Conclusion Using MS-GUIDE we identified fibronectin and vitronectin as candidate biomarkers for prostate cancer risk stratification.
      PubDate: 2022-04-27
       
  • Moving translational mass spectrometry imaging towards transparent and
           reproducible data analyses: a case study of an urothelial cancer cohort
           analyzed in the Galaxy framework

    • Abstract: Background Mass spectrometry imaging (MSI) derives spatial molecular distribution maps directly from clinical tissue specimens and thus bears great potential for assisting pathologists with diagnostic decisions or personalized treatments. Unfortunately, progress in translational MSI is often hindered by insufficient quality control and lack of reproducible data analysis. Raw data and analysis scripts are rarely publicly shared. Here, we demonstrate the application of the Galaxy MSI tool set for the reproducible analysis of a urothelial carcinoma dataset. Methods Tryptic peptides were imaged in a cohort of 39 formalin-fixed, paraffin-embedded human urothelial cancer tissue cores with a MALDI-TOF/TOF device. The complete data analysis was performed in a fully transparent and reproducible manner on the European Galaxy Server. Annotations of tumor and stroma were performed by a pathologist and transferred to the MSI data to allow for supervised classifications of tumor vs. stroma tissue areas as well as for muscle-infiltrating and non-muscle infiltrating urothelial carcinomas. For putative peptide identifications, m/z features were matched to the MSiMass list. Results Rigorous quality control in combination with careful pre-processing enabled reduction of m/z shifts and intensity batch effects. High classification accuracy was found for both, tumor vs. stroma and muscle-infiltrating vs. non-muscle infiltrating urothelial tumors. Some of the most discriminative m/z features for each condition could be assigned a putative identity: stromal tissue was characterized by collagen peptides and tumor tissue by histone peptides. Immunohistochemistry confirmed an increased histone H2A abundance in the tumor compared to the stroma tissues. The muscle-infiltration status was distinguished via MSI by peptides from intermediate filaments such as cytokeratin 7 in non-muscle infiltrating carcinomas and vimentin in muscle-infiltrating urothelial carcinomas, which was confirmed by immunohistochemistry. To make the study fully reproducible and to advocate the criteria of FAIR (findability, accessibility, interoperability, and reusability) research data, we share the raw data, spectra annotations as well as all Galaxy histories and workflows. Data are available via ProteomeXchange with identifier PXD026459 and Galaxy results via https://github.com/foellmelanie/Bladder_MSI_Manuscript_Galaxy_links. Conclusion Here, we show that translational MSI data analysis in a fully transparent and reproducible manner is possible and we would like to encourage the community to join our efforts.
      PubDate: 2022-04-19
       
  • Data-independent acquisition mass spectrometry in severe rheumatic heart
           disease (RHD) identifies a proteomic signature showing ongoing
           inflammation and effectively classifying RHD cases

    • Abstract: Background Rheumatic heart disease (RHD) remains a major source of morbidity and mortality in developing countries. A deeper insight into the pathogenetic mechanisms underlying RHD could provide opportunities for drug repurposing, guide recommendations for secondary penicillin prophylaxis, and/or inform development of near-patient diagnostics. Methods We performed quantitative proteomics using Sequential Windowed Acquisition of All Theoretical Fragment Ion Mass Spectrometry (SWATH-MS) to screen protein expression in 215 African patients with severe RHD, and 230 controls. We applied a machine learning (ML) approach to feature selection among the 366 proteins quantifiable in at least 40% of samples, using the Boruta wrapper algorithm. The case–control differences and contribution to Area Under the Receiver Operating Curve (AUC) for each of the 56 proteins identified by the Boruta algorithm were calculated by Logistic Regression adjusted for age, sex and BMI. Biological pathways and functions enriched for proteins were identified using ClueGo pathway analyses. Results Adiponectin, complement component C7 and fibulin-1, a component of heart valve matrix, were significantly higher in cases when compared with controls. Ficolin-3, a protein with calcium-independent lectin activity that activates the complement pathway, was lower in cases than controls. The top six biomarkers from the Boruta analyses conferred an AUC of 0.90 indicating excellent discriminatory capacity between RHD cases and controls. Conclusions These results support the presence of an ongoing inflammatory response in RHD, at a time when severe valve disease has developed, and distant from previous episodes of acute rheumatic fever. This biomarker signature could have potential utility in recognizing different degrees of ongoing inflammation in RHD patients, which may, in turn, be related to prognostic severity.
      PubDate: 2022-03-22
       
  • Integrative omics reveals subtle molecular perturbations following
           ischemic conditioning in a porcine kidney transplant model

    • Abstract: Background Remote Ischemic Conditioning (RIC) has been proposed as a therapeutic intervention to circumvent the ischemia/reperfusion injury (IRI) that is inherent to organ transplantation. Using a porcine kidney transplant model, we aimed to decipher the subclinical molecular effects of a RIC regime, compared to non-RIC controls. Methods Kidney pairs (n = 8 + 8) were extracted from brain dead donor pigs and transplanted in juvenile recipient pigs following a period of cold ischemia. One of the two kidney recipients in each pair was subjected to RIC prior to kidney graft reperfusion, while the other served as non-RIC control. We designed an integrative Omics strategy combining transcriptomics, proteomics, and phosphoproteomics to deduce molecular signatures in kidney tissue that could be attributed to RIC. Results In kidney grafts taken out 10 h after transplantation we detected minimal molecular perturbations following RIC compared to non-RIC at the transcriptome level, which was mirrored at the proteome level. In particular, we noted that RIC resulted in suppression of tissue inflammatory profiles. Furthermore, an accumulation of muscle extracellular matrix assembly proteins in kidney tissues was detected at the protein level, which may be in response to muscle tissue damage and/or fibrosis. However, the majority of these protein changes did not reach significance (p < 0.05). Conclusions Our data identifies subtle molecular phenotypes in porcine kidneys following RIC, and this knowledge could potentially aid optimization of remote ischemic conditioning protocols in renal transplantation.
      PubDate: 2022-02-14
      DOI: 10.1186/s12014-022-09343-3
       
  • Quantitative proteomic analysis of serum-purified exosomes identifies
           putative pre-eclampsia-associated biomarkers

    • Abstract: Background The high incidence of pre-eclampsia, which affects 2–7% of all pregnancies, remains a major health concern. Detection of pre-eclampsia before the appearance of clinical symptoms is essential to allow early intervention, and would benefit from identification of plasma/serum biomarkers to help guide diagnosis and treatment. Liquid biopsy has emerged as a promising source of protein biomarkers that circumvents some of the inherent challenges of proteome-wide analysis of plasma/serum. In this respect, purified exosomes have the added benefit of being carriers of intercellular communication both in physiological and pathological conditions. Methods We compared the protein complement of purified exosomes from three different collections of control and pre-eclamptic serum samples, obtained at the end of the second trimester of pregnancy and at delivery. We employed shotgun label-free proteomics to investigate differential protein expression, which was then validated by targeted proteomics. Results We developed a purification method that yielded highly enriched exosome preparations. The presence of specific pregnancy protein markers suggested that a significant proportion of purified exosomes derived from tissues related to pregnancy. Quantitative proteomic analyses allowed us to identify 10, 114 and 98 differentially-regulated proteins in the three sample collections, with a high degree of concordance. Functional analysis suggested that these proteins participate in biological processes related to pre-eclampsia, including angiogenesis, inflammation and cell migration. The differential abundance of 66 proteins was validated by targeted proteomics. Finally, we studied the impact of the pre-eclampsia-associated exosomes in the proteome using an in vitro cellular model. Conclusions We have identified and validated differential exosomal proteins in liquid biopsy of pregnant women that open new possibilities for early detection of pre-eclampsia. Additionally, the functional impact of the proteome composition of purified pre-eclamptic exosomes in target cells provides new information to better understand changes in embryo-maternal interactions and, consequently, the pathogenesis of this disease.
      PubDate: 2022-02-10
      DOI: 10.1186/s12014-022-09342-4
       
  • Secreted protein markers in oral squamous cell carcinoma (OSCC)

    • Abstract: Background Oral squamous cell carcinoma (OSCC) is a main cause of oral cancer mortality and morbidity in central south Asia. To improve the clinical outcome of OSCC patients, detection markers are needed, which are preferably non-invasive and thus independent of a tissue biopsy. Methods In the present study, we aimed to identify robust candidate protein biomarkers for non-invasive OSCC diagnosis. To this end, we measured the global protein profiles of OSCC tissue lysates to matched normal adjacent mucosa samples (n = 14) and the secretomes of nine HNSCC cell lines using LC–MS/MS-based proteomics. Results A total of 5123 tissue proteins were identified, of which 205 were robustly up- regulated (p-value < 0.01, fold change > + 2) in OSCC-tissues compared to normal adjacent tissues. The biological process “Secretion” was highly enriched in this set of proteins. Other upregulated biological pathways included “Unfolded Protein Response”, “Spliceosomal complex assembly”, “Protein localization to endosome” and “Interferon Gamma Response”. Transcription factor analysis implicated Creb3L1, ESRRA, YY, ELF2, STAT1 and XBP as potential regulators. Of the 205 upregulated tissue proteins, 132 were identified in the cancer cell line secretomes, underscoring their potential use as non-invasive biofluid markers. To further prioritize our candidate markers for non-invasive OSCC detection, we integrated our data with public biofluid datasets including OSCC saliva, yielding 25 candidate markers for further study. Conclusions We identified several key proteins and processes that are associated with OSCC tissues, underscoring the importance of altered secretion. Cancer-associated OSCC secretome proteins present in saliva have potential to be used as novel non-invasive biomarkers for the diagnosis of OSCC. Graphical
      PubDate: 2022-02-08
      DOI: 10.1186/s12014-022-09341-5
       
  • Identification of biomarkers of chronic kidney disease among
           kidney-derived proteins

    • Abstract: Background Chronic kidney disease (CKD) has few objective symptoms, and it is difficult to make an early diagnosis by using existing methods. Therefore, new biomarkers enabling diagnosis of renal dysfunction at an early stage need to be developed. Here, we searched for new biomarkers of CKD by focusing on kidney-derived proteins that could sensitively reflect that organ’s disease state. Methods To identify candidate marker proteins, we performed a proteomics analysis on renal influx and efflux blood collected from the same individual. Results Proteomics analysis revealed 662 proteins in influx blood and 809 in efflux. From these identified proteins, we selected complement C1q as a candidate; the plasma C1q level was significantly elevated in the renal efflux of donors. Moreover, the plasma concentration of C1q in a mouse model of diabetic nephropathy was significantly increased, in association with increases in blood glucose concentration and urinary protein content. Importantly, we demonstrated that the tendency of C1q to increase in the plasma of CKD patients was correlated with a decrease in their estimated glomerular filtration rate. Conclusion Overall, our results indicate that our approach of focusing on kidney-derived proteins is useful for identifying new CKD biomarkers and that C1q has potential as a biomarker of renal function.
      PubDate: 2022-01-11
      DOI: 10.1186/s12014-021-09340-y
       
  • Circulating microvesicles and exosomes in small cell lung cancer by
           quantitative proteomics

    • Abstract: Background Early detection of small cell lung cancer (SCLC) crucially demands highly reliable markers. Growing evidence suggests that extracellular vesicles carry tumor cell-specific cargo suitable as protein markers in cancer. Quantitative proteomic profiling of circulating microvesicles and exosomes can be a high-throughput platform for discovery of novel molecular insights and putative markers. Hence, this study aimed to investigate proteome dynamics of plasma-derived microvesicles and exosomes in newly diagnosed SCLC patients to improve early detection. Methods Plasma-derived microvesicles and exosomes from 24 healthy controls and 24 SCLC patients were isolated from plasma by either high-speed- or ultracentrifugation. Proteins derived from these extracellular vesicles were quantified using label-free mass spectrometry and statistical analysis was carried out aiming at identifying significantly altered protein expressions between SCLC patients and healthy controls. Furthermore, significantly expressed proteins were subjected to functional enrichment analysis to identify biological pathways implicated in SCLC pathogenesis. Results Based on fold change (FC) ≥ 2 or ≤ 0.5 and AUC ≥ 0.70 (p < 0.05), we identified 10 common and 16 and 17 unique proteins for microvesicles and exosomes, respectively. Among these proteins, we found dysregulation of coagulation factor XIII A (Log2 FC =  − 1.1, p = 0.0003, AUC = 0.82, 95% CI: 0.69–0.96) and complement factor H-related protein 4 (Log2 FC = 1.2, p = 0.0005, AUC = 0.82, 95% CI; 0.67–0.97) in SCLC patients compared to healthy individuals. Our data may indicate a novel tumor-suppressing role of blood coagulation and involvement of complement activation in SCLC pathogenesis. Conclusions In comparing SCLC patients and healthy individuals, several differentially expressed proteins were identified. This is the first study showing that circulating extracellular vesicles may encompass specific proteins with potential diagnostic attributes for SCLC, thereby opening new opportunities as novel non-invasive markers.
      PubDate: 2022-01-07
      DOI: 10.1186/s12014-021-09339-5
       
  • Uncomplicated Plasmodium vivax malaria: mapping the proteome from
           circulating platelets

    • Abstract: Background Thrombocytopenia is frequent in Plasmodium vivax malaria but the role of platelets in pathogenesis is unknown. Our study explores the platelet (PLT) proteome from uncomplicated P. vivax patients, to fingerprint molecular pathways related to platelet function. Plasma levels of Platelet factor 4 (PF4/CXCL4) and Von Willebrand factor (VWf), as well as in vitro PLTs—P. vivax infected erythrocytes (Pv-IEs) interactions were also evaluated to explore the PLT response and effect on parasite development. Methods A cohort of 48 patients and 25 healthy controls were enrolled. PLTs were purified from 5 patients and 5 healthy controls for Liquid Chromatography–Mass spectrometry (LC–MS/MS) analysis. Plasma levels of PF4/CXCL4 and VWf were measured in all participants. Additionally, P. vivax isolates (n = 10) were co-cultured with PLTs to measure PLT activation by PF4/CXCL4 and Pv-IE schizonts formation by light microscopy. Results The proteome from uncomplicated P. vivax patients showed 26 out of 215 proteins significantly decreased. PF4/CXCL4 was significantly decreased followed by other proteins involved in platelet activation, cytoskeletal remodeling, and endothelial adhesion, including glycoprotein V that was significantly decreased in thrombocytopenic patients. In contrast, acute phase proteins, including SERPINs and Amyloid Serum A1 were increased. High levels of VWf in plasma from patients suggested endothelial activation while PF4/CXCL4 plasma levels were similar between patients and controls. Interestingly, high levels of PF4/CXCL4 were released from PLTs—Pv-IEs co-cultures while Pv-IEs schizont formation was inhibited. Conclusions The PLT proteome analyzed in this study suggests that PLTs actively respond to P. vivax infection. Altogether, our findings suggest important roles of PF4/CXCL4 during uncomplicated P. vivax infection through a possible intracellular localization. Our study shows that platelets are active responders to P. vivax infection, inhibiting intraerythrocytic parasite development. Future studies are needed to further investigate the molecular pathways of interaction between platelet proteins found in this study and host response, which could affect parasite control as well as disease progression.
      PubDate: 2022-01-05
      DOI: 10.1186/s12014-021-09337-7
       
  • Urine proteomics identifies biomarkers for diabetic kidney disease at
           different stages

    • Abstract: Background Type 2 diabetic kidney disease is the most common cause of chronic kidney diseases (CKD) and end-stage renal diseases (ESRD). Although kidney biopsy is considered as the ‘gold standard’ for diabetic kidney disease (DKD) diagnosis, it is an invasive procedure, and the diagnosis can be influenced by sampling bias and personal judgement. It is desirable to establish a non-invasive procedure that can complement kidney biopsy in diagnosis and tracking the DKD progress. Methods In this cross-sectional study, we collected 252 urine samples, including 134 uncomplicated diabetes, 65 DKD, 40 CKD without diabetes and 13 follow-up diabetic samples, and analyzed the urine proteomes with liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). We built logistic regression models to distinguish uncomplicated diabetes, DKD and other CKDs. Results We quantified 559 ± 202 gene products (GPs) (Mean ± SD) on a single sample and 2946 GPs in total. Based on logistic regression models, DKD patients could be differentiated from the uncomplicated diabetic patients with 2 urinary proteins (AUC = 0.928), and the stage 3 (DKD3) and stage 4 (DKD4) DKD patients with 3 urinary proteins (AUC = 0.949). These results were validated in an independent dataset. Finally, a 4-protein classifier identified putative pre-DKD3 patients, who showed DKD3 proteomic features but were not diagnosed by clinical standards. Follow-up studies on 11 patients indicated that 2 putative pre-DKD patients have progressed to DKD3. Conclusions Our study demonstrated the potential for urinary proteomics as a noninvasive method for DKD diagnosis and identifying high-risk patients for progression monitoring.
      PubDate: 2021-12-29
      DOI: 10.1186/s12014-021-09338-6
       
  • Integration of transcriptome and proteome profiles in placenta accreta
           reveals trophoblast over-migration as the underlying pathogenesis

    • Abstract: Background Placenta accreta (PA) is a major cause of maternal morbidity and mortality in modern obstetrics, few studies have explored the underlying molecular mechanisms. Methods In our study, transcriptome and proteome profiling were performed in placental tissues from ten participants including five cases each in the PA and control groups to clarify the pathogenesis of PA. Results We identified differential expression of 37,743 transcripts and 160 proteins between the PA and control groups with an overlap rate of 0.09%. The 33 most-significant transcripts and proteins were found and further screened and analyzed. Adhesion-related signature, chemotaxis related signatures and immune related signature were found in the PA group and played a certain role. Sum up two points, three significant indicators, methyl-CpG-binding domain protein 2 (MeCP2), podocin (PODN), and apolipoprotein D (ApoD), which participate in “negative regulation of cell migration”, were downregulated at the mRNA and protein levels in PA group. Furthermore, transwell migration and invasion assay of HTR-8/SVneo cell indicated the all of them impaired the migration and invasion of trophoblast. Conclusion A poor correlation was observed between the transcriptome and proteome data and MeCP2, PODN, and ApoD decreased in transcriptome and proteome profiling, resulting in increased migration of trophoblasts in the PA group, which clarify the mechanism of PA and might be the biomarkers or therapy targets in the future.
      PubDate: 2021-12-29
      DOI: 10.1186/s12014-021-09336-8
       
  • Proteomics and functional study reveal kallikrein-6 enhances communicating
           hydrocephalus

    • Abstract: Background Communicating hydrocephalus (CH) is a common neurological disorder caused by a blockage of cerebrospinal fluid. In this study, we aimed to explore the potential molecular mechanism underlying CH development. Methods Quantitative proteomic analysis was performed to screen the differentially expressed proteins (DEPs) between patients with and without CH. A CH rat model was verified by Hoechst staining, and the co-localization of the target protein and neuron was detected using immunofluorescence staining. Loss-of-function experiments were performed to examine the effect of KLK6 on the synapse structure. Results A total of 11 DEPs were identified, and kallikrein 6 (KLK6) expression was found to be significantly upregulated in patients with CH compared with that in patients without CH. The CH rat model was successfully constructed, and KLK6 was found to be co-localized with neuronal nuclei in brain tissue. The expression level of IL-1β, TNF-α, and KLK6 in the CH group was higher than that in the control group. After knockdown of KLK6 expression using small-interfering RNA (siRNA), the expression levels of synapsin-1 and PSD95 in neuronal cells were increased, and the length, number, and structure of synapses were significantly improved. Following siRNA interference KLK6 expression, 5681 differentially expressed genes (DEGs) were identified in transcriptome profile. The upregulated DEGs of Appl2, Nav2, and Nrn1 may be involved in the recovery of synaptic structures after the interference of KLK6 expression. Conclusions Collectively, KLK6 participates in the development of CH and might provide a new target for CH treatment.
      PubDate: 2021-12-16
      DOI: 10.1186/s12014-021-09335-9
       
 
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