Common Metabolic Pathways Implicated in Resistance to Chemotherapy Point to a Key Mitochondrial Role in Breast Cancer,

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Highlights

• •OMICS distinguish cancer cells from resistant or cancer stem cells.
• •Bactericidal antibiotics and mitochondria.
• •Linezolid and anticancer therapy.

     

Metabolic,Anti-apoptotic and Immune Evasion Strategies of Primary Human Myeloma Cells Indicate Adaptations to Hypoxia*

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Highlights

• •In-depth proteome profiling of primary human myeloma cells
• •Characteristics of myeloma cells are related to hypoxic bone marrow conditions
• •Myeloma cells show specific immune evasion strategies
• •Metabolic adaptations involve tumor and stroma cells

     

Chromobodies to Quantify Changes of Endogenous Protein Concentration in Living Cells

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Highlights

• •Chromobodies are stabilized by antigen binding in live cells.
• •Monitoring changes of endogenous protein levels in living cells with chromobodies.
• •Broadly applicable system to generate turnover-accelerated chromobodies.
• •Quantification of time- and dose-dependent compound effects.

     

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.

     

DECA,A Comprehensive,Automatic Post-processing Program for HDX-MS Data*

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Highlights

• •Open source software for comprehensive HDX-MS data analysis.
• •Automatic back-exchange correction options.
• •Rigorous statistical analysis of the significance of uptake differences.
• •High quality visualization tools.

     

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.

     

A New Tool to Reveal Bacterial Signaling Mechanisms in Antibiotic Treatment and Resistance

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Highlights

• •Quantitative (phospho)proteome analysis of antibiotic treatment in E. coli.
• •Largest bacterial phosphorylation catalogue.
• •Specific phosphorylation motifs changes during resistance development.
• •Phosphorylation mediated signaling could be a potential target for drug design.

     

Metabolic Cross-talk Between Human Bronchial Epithelial Cells and Internalized Staphylococcus aureus as a Driver for Infection*

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Highlights

• •Interplay of epithelial cells and internalized S. aureus was dissected over 96 h.
• •Surviving host cells contain nonreplicating bacteria that persists in the cytoplasm.
• •Competition over resources triggers temporal metabolic changes.
• •Metabolic adaptation of host and bacteria determines the outcome of infection.

     

High-density Peptide Arrays Help to Identify Linear Immunogenic B-cell Epitopes in Individuals Naturally Exposed to Malaria Infection

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Highlights

• •Profiling antibody responses of patients with naturally acquired malaria immunity.
• •High-density peptide arrays featuring linear epitopes.
• •Epitope mapping of known and potential novel vaccine candidates.
• •Novel immunogenic epitopes discovered, and known antibody target motifs confirmed.

     

High-throughput Identification of FLT3 Wild-type and Mutant Kinase Substrate Preferences and Application to Design of Sensitive In Vitro Kinase Assay Substrates

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Highlights

• •Developed a data processing pipeline to format phosphopeptide identifications.
• •Identified the preferred substrate motif for FLT3 and mutant kinases.
• •Designed and validated a panel of pan-FTL3 artificial substrates.
• •Monitored FLT3 and mutant kinase activity through FAStide phosphorylation.

     

HLA-DO Modulates the Diversity of the MHC-II Self-peptidome

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Highlights

• •MHC-II-bound peptide repertoires from DO-sufficient and DO-deficient cells.
• •Fewer unique peptides and core epitopes were presented in the absence of DO.
• •Immunopeptidome differences appeared to result from reduced DM editing.
• •DO-dependent self-epitopes elicited CD4 T cell responses in mice.

     

Macrophage Phosphoproteome Analysis Reveals MINCLE-dependent and -independent Mycobacterial Cord Factor Signaling

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Highlights

• •quantitative phosphoproteome analysis of TDM-activated macrophages.
• •distinct Mincle-dependent and independent phosphorylation and gene regulations.
• •Mincle-dependent activation of PI3K/AKT signaling by TDM.
• •Mincle-independent macrophage response is linked to cell cycle regulation.

     

Sensitive Determination of Proteolytic Proteoforms in Limited Microscale Proteome Samples

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Highlights

• •Single-pot workflow for manual or automated enrichment of N-terminal peptides.
• •Sensitive enrichment of protein N termini from 10,000 cells or 2 μg crude proteome.
• •Data independent acquisition improves precision of peptide level quantification.
• •First degradomic analyses of sorted immune cells, single seedlings, and mitochondria from patient cells.

     

Proteomic Analysis of Vocal Fold Fibroblasts Exposed to Cigarette Smoke Extract: Exploring the Pathophysiology of Reinke's Edema,

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Highlights

• •First global study on laryngeal cells cultured with cigarette smoke enriched medium.
• •Vocal fold fibroblasts increased production of ECM component hyaluronan.
• •Expression of several fibrillar collagens was reduced.

     

Mapping Spatiotemporal Microproteomics Landscape in Experimental Model of Traumatic Brain Injury Unveils a link to Parkinson's Disease,

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Highlights

• •Spatiotemporal microproteomics analysis of TBI.
• •Injury site microproteomics reveal distinct phases in 10-day frame post TBI.
• •Uninjured proteomic profile is restored in TBI at 10 days post injury.
• •Substantia nigra protein post 3 days suggest link to Parkinson's disease.

     

Why Glycosylation Matters in Building a Better Flu Vaccine

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Highlights

• •Glycosylation is not currently considered in flu vaccine design.
• •Glycosylation influences on immunodominance are not well understood.
• •Identification of site-specific glycosylation using mass spectrometry has matured.
• •New methods are needed to quantify site-specific glycosylation for vaccine design.