Reductive Stress Selectively Disrupts Collagen Homeostasis and Modifies Growth Factor-independent Signaling Through the MAPK/Akt Pathway in Human Dermal Fibroblasts

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Highlights

• •Changes to the proteome of skin fibroblasts subjected to reductive stress have been quantitated.
• •Only a small set of proteins is selectively diminished upon exposure to reductants.
• •Collagens (COL1A2 and COL6A2) emerge as sentinels of reductive stress.
• •Reductive stress triggers receptor-independent Akt phosphorylation at Ser473.

     

MS-EmpiRe Utilizes Peptide-level Noise Distributions for Ultra-sensitive Detection of Differentially Expressed Proteins

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Highlights

• •New software to determine differentially expressed proteins in quantitative MS experiments.
• •Applicable to any modern quantitative MS setup and study type, including clinical setups.
• •Ultra-sensitive at strict FDR control, up to 1000 additional proteins in a single comparison.
• •Easy to use, fast processing and readily available package, including user friendly manual.

     

Changes in Synaptic Proteins Precede Neurodegeneration Markers in Preclinical Alzheimer's Disease Cerebrospinal Fluid

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Highlights

• •Proteomic analysis of cerebrospinal fluid and identification of synaptic component.
• •Use of super resolution microscopy to verify synapse-specificity in human tissue.
• •Selective reaction monitoring MS (SRM) of synaptic panel in 3 cohorts of Alzheimer's disease cerebrospinal fluid.
• •Synaptic protein changes precede tau in preclinical Alzheimer's disease.

     

A Combined N-terminomics and Shotgun Proteomics Approach to Investigate the Responses of Human Cells to Rapamycin and Zinc at the Mitochondrial Level

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Highlights

• •Rapamycin and zinc induce moderate but significant mitochondrial proteome changes.
• •The mitochondrial proteins processing system is robust under subtoxic conditions.
• •Rapamycin and zinc perturb the mitochondrial proteins processing system.
• •Rapamycin and zinc perturb the mitochondrial proteins homeostasis.

     

Development of a Gill Assay Library for Ecological Proteomics of Threespine Sticklebacks (Gasterosteus aculeatus)

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Highlights

• •Construction of threespine stickleback gill assay library using DDA proteomics
• •Population-specific gill proteome signatures of four ecotypes identified by DIA
• •HSP47 and extracellular matrix proteins highly elevated in warm-adapted sticklebacks
• •Inflammasome and proteolytic proteins highly elevated in freshwater sticklebacks

     

Multi-omics Biomarker Pipeline Reveals Elevated Levels of Protein-glutamine Gamma-glutamyltransferase 4 in Seminal Plasma of Prostate Cancer Patients

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Highlights

• •Seventy-six most promising proteins were qualified, and 19 proteins were verified by SRM in 219 seminal plasma samples of patients with prostate cancer and negative biopsies.
• •Prostate-specific, secreted and androgen-regulated protein-glutamine gamma-glutamyltransferase 4 (TGM4) was verified by SRM assay and an in-house immunoassay.
• •TGM4 detected prostate cancer on biopsy in seminal plasma (AUC=0.66), but not in blood serum.

     

Comprehensive Analysis of the Lysine Succinylome and Protein Co-modifications in Developing Rice Seeds

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Highlights

• •Nonenzymatically Ksu proteins shown different pattern from native cell Ksu proteins.
• •Motif preference of Ksu proteins was associated with different biological processes.
• •Up to 67 developing rice seeds proteins contain PTMs of Kac, Ksu, Kcr, Kmal, and Khib.
• •Some lysine residues of the key pathway enzymes are modified by succinylation.

     

Cross-linking Proteomics Indicates Effects of Simvastatin on the TLR2 Interactome and Reveals ACTR1A as a Novel Regulator of the TLR2 Signal Cascade

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Highlights

• •An innovative co-IP crosslinking proteomics study was designed for the TLR2 interactome.
• •Proteomic profiling revealed combinatorial effects of simvastatin and Pam3CSK4 on the TLR2 interactome.
• •ACTR1A and MARCKSL1 proteins were identified as potential interactors of TLR2 during the immune response.
• •ACTR1A has important modulatory actions on the TLR2 pro-inflammatory signaling cascade.

     

Spatiotemporal Changes of the Phagosomal Proteome in Dendritic Cells in Response to LPS Stimulation*

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Highlights

• •Characterization of the phagosomal proteome comparing resting and LPS-treated BMDCs.
• •Label-free quantification determined 2843 phagosomal proteins.
• •Reduced recruitment of hydrolases and V-ATPase to phagosomes of LPS-treated cells.
• •Increased recruitment of antigen cross-presentation molecules to these phagosomes.

     

Global Interactomics Uncovers Extensive Organellar Targeting by Zika Virus

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Highlights

• •BioID and IP-MS were conducted to generate a global ZIKV-host protein interactome
• •Interactome consists of >3000 high confidence ZIKV-host protein interactions
• •Data mining indicates that ZIKV proteins interact with multiple host cell organelles
• •An important role for peroxisomes in ZIKV infection is uncovered

     

Hepatic Mitochondrial Defects in a Nonalcoholic Fatty Liver Disease Mouse Model Are Associated with Increased Degradation of Oxidative Phosphorylation Subunits

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Highlights

• •Stability of oxidative phosphorylation subunits are reduced in a diet-induced mouse model of NAFLD.
• •These changes are associated with impaired activities of electron transport chain complexes and ATP synthesis.
• •Increased mitophagy contributed to enhanced degradation of mitochondrial proteins.

     

Comprehensive Analysis of Individual Variation in the Urinary Proteome Revealed Significant Gender Differences

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Highlights

• •Comprehensive analysis of inter-individual variation of normal urinary proteome.
• •Significant gender differences were observed.
• •Proteins increased in female urine are enriched in immunological pathways.
• •Estimated reference intervals of proteins as the baseline for biomarker discovery.

     

Nonparametric Analysis of Thermal Proteome Profiles Reveals Novel Drug-binding Proteins*

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Highlights

• •Method for the analysis of response curves from thermal proteome profiling (TPP).
• •NPARC uses nonparametric statistics and provides false discovery-rate (FDR) control.
• •Increased proteome coverage and sensitivity to identify drug-binding proteins.

     

Dynamic Phosphoproteomics Uncovers Signaling Pathways Modulated by Anti-oncogenic Sphingolipid Analogs

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Highlights

• •Quantitative phosphoproteomics of cells treated with sphingolipid analogs or PP2A inhibitor identify novel protein targets of PP2A.
• •PP2A substrates include several nutrient transporter proteins, GTPase regulators and proteins associated with actin cytoskeletal remodeling.
• •Differential regulation of Akt and Gsk3b account for the difference in vacuolating phenotype observed between SH-BC-893 and C2-ceramide.
• •Dynamic phosphoproteomics enabled the correlation of cell signaling with phenotypes to rationalize their mode of action.

     

Analysis of Brain and Cerebrospinal Fluid from Mouse Models of the Three Major Forms of Neuronal Ceroid Lipofuscinosis Reveals Changes in the Lysosomal Proteome

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Highlights

• •Proteomic analysis of brain and cerebrospinal fluid from mouse NCL models.
• •Disease-associated changes in lysosomal proteins and markers of neuroinflammation.
• •Biomarker candidates identified for further evaluation.

     

Deciphering Protein Glycosylation by Computational Integration of On-chip Profiling,Glycan-array Data,and Mass Spectrometry

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Highlights

• •Method to probe the isomeric variants of the glycans attached to purified proteins.
• •Uses multiple rounds of glycosidase cleavage and lectin profiling.
• •Computation integration of lectin-binding, glycan-array, and mass spectrometry data.
• •Applied to microspots for compatibility with analyzing low-abundance proteins.

     

A High-throughput Bead-based Affinity Assay Enables Analysis of Genital Protein Signatures in Women At Risk of HIV Infection

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Highlights

• •Genital samples were analyzed using a high-throughput bead-based affinity assay.
• •Proteins were validated by tandem mass spectrometry with concordant results.
• •Genital epithelial proteins were increased in HIV-serodiscordant women.