Understanding PACS2 syndrome’s pathomechanism by studying E209K and E211K mutations DOI
Arkadiusz Żbikowski, Tomasz Kowalczyk, Petr Kašpárek

et al.

Mammalian Genome, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 30, 2024

Language: Английский

The molecular diversity of hippocampal regions and strata at synaptic resolution revealed by integrated transcriptomic and proteomic profiling DOI Creative Commons
Eva Kaulich,

Quinn Waselenchuk,

N Furst

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 5, 2024

ABSTRACT The molecular diversity of neurons and their synapses underlies the different responses plasticity profiles that drive all neural circuits behavior. While extent this has been partially revealed by transcriptomic proteomic profiling, combined studies neuronal transcripts proteins are limited. Here, we used microdissection mouse hippocampal subregions CA1 strata fluorescence-activated synaptosome sorting (FASS) to characterize from compartments with synaptic resolution. Parallel RNA-seq LC-MS/MS microdissections identified over 15,000 mRNA 10,000 proteins, revealing thousands local enrichment such as classes glutamate receptors voltage-gated potassium channels, myelin-associated molecules, adhesion molecules. Synaptosome analysis further specific molecules collagen, ribosome, solute carrier, receptor families at formed along neurons. By integrating protein data, defined clusters co-regulated neurofilament transporter mRNAs, found subsets mRNA-protein pairs strong correlation anti-correlation in abundance variation. Our findings comprise a rich resource on landscape hippocampus its is accessible syndive.org , highlight coordinated organization between regions, compartments, synapses.

Language: Английский

Citations

1
Systematic Optimization of Activity-Based Protein Profiling for Identification of Polysorbate-Degradative Enzymes in Biotherapeutic Drug Substance down to 10 ppb DOI
Taku Tsukidate, Anita P. Liu, Shannon Rivera

et al.

Journal of the American Society for Mass Spectrometry, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 21, 2024

The identification and control of high-risk host cell proteins (HCPs) in biotherapeutics development are crucial for ensuring product quality shelf life. Specifically, HCPs with hydrolase activity can cause the degradation excipient polysorbates (PS), leading to a decrease life drug product. In this study, we systematically optimized every step an activity-based protein profiling (ABPP) workflow identify trace amounts active polysorbate-degradative enzymes (PSDEs) biotherapeutic process intermediates. Evaluation various parameters during sample preparation pinpointed optimal pH level fluorophosphonate (FP)-biotin concentration. Moreover, combined use short liquid chromatography gradient fast-scanning parallel accumulation–serial fragmentation (PASEF) methodology increased throughput without compromising coverage. Tuning trapped ion mobility spectrometry (TIMS) further enhanced sensitivity. addition, evaluated data acquisition modes, including PASEF data-dependent (DDA PASEF), data-independent (diaPASEF), or reaction monitoring (prm-PASEF). By employing newly ABPP workflow, successfully identified PSDEs at concentration as low 10 ppb substance sample. Finally, new enabled us detect PSDE that could not be detected original PS root-cause investigation.

Language: Английский

Citations

1
Regional and longitudinal dynamics of human milk protein components assessed by proteome analysis on a fast and robust micro-flow LC–MS/MS system DOI

Junxia Cao,

Xinling Cui, Haiyan Lu

et al.

Food Chemistry, Journal Year: 2024, Volume and Issue: 465, P. 141981 - 141981

Published: Nov. 9, 2024

Language: Английский

Citations

0
Pan-cancer N-glycoproteomic atlas of patient derived xenografts uncovers FAT2 as a therapeutic target for head and neck cancers DOI Open Access

Meinusha Govindarajan,

Salvador Mejia‐Guerrero,

Shawn C. Chafe

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 14, 2024

Cell surface proteins offer significant cancer therapeutic potential attributable to their accessible membrane localization and central role in cellular signaling. Despite this, promise remains largely untapped due the technical challenges inherent profiling cell proteins. Here, we employed N-glycoproteomics analyze 85 patient-derived xenografts (PDX), constructing Glyco PDXplorer - an vivo pan-cancer atlas of cancer-derived We developed a target discovery pipeline prioritize with favorable expression profiles for immunotherapeutic targeting validated FAT2 as head neck squamous (HNSC) enriched protein limited normal tissue. Functional studies revealed that is essential HNSC growth adhesion through regulation architecture integrin-PI3K Chimeric antigen receptor (CAR) T cells demonstrated potent anti-tumor activity models. This work lays foundation developing FAT2-targeted therapies represents pivotal resource inform multiple cancers.

Language: Английский

Citations

0
Understanding PACS2 syndrome’s pathomechanism by studying E209K and E211K mutations DOI
Arkadiusz Żbikowski, Tomasz Kowalczyk, Petr Kašpárek

et al.

Mammalian Genome, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 30, 2024

Language: Английский

Citations

0