Caused by Yersinia pestis, plague ravaged the world through three known pandemics: the First or the Justinianic (6th-8th century); the Second (beginning with the Black Death during c.1338-1353 and lasting until the 19th century); and the Third (which became global in 1894). It is debatable whether Y. pestis persisted in European wildlife reservoirs or was repeatedly introduced from outside Europe (as covered by European Union and the British Isles). Here, we analyze environmental data (soil characteristics and climate) from active Chinese plague reservoirs to assess whether such environmental conditions in Europe had ever supported "natural plague reservoirs". We have used new statistical methods which are validated through predicting the presence of modern plague reservoirs in the western United States. We find no support for persistent natural plague reservoirs in either historical or modern Europe. Two factors make Europe unfavorable for long-term plague reservoirs: 1) Soil texture and biochemistry and 2) low rodent diversity. By comparing rodent communities in Europe with those in China and the United States, we conclude that a lack of suitable host species might be the main reason for the absence of plague reservoirs in Europe today. These findings support the hypothesis that long-term plague reservoirs did not exist in Europe and therefore question the importance of wildlife rodent species as the primary plague hosts in Europe.

• Klíčová slova
• Europe, Yersinia pestis, environmental conditions, natural plague reservoirs, rodent diversity,
• MeSH
• lidé MeSH
• mor * epidemiologie   dějiny   MeSH
• pandemie dějiny   MeSH
• podnebí MeSH
• půda MeSH
• Yersinia pestis * MeSH
• zdroje nemoci MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• půda MeSH

To date, the effects of specific modification types and sites on protein lifetime have not been systematically illustrated. Here, we describe a proteomic method, DeltaSILAC, to quantitatively assess the impact of site-specific phosphorylation on the turnover of thousands of proteins in live cells. Based on the accurate and reproducible mass spectrometry-based method, a pulse labeling approach using stable isotope-labeled amino acids in cells (pSILAC), phosphoproteomics, and a unique peptide-level matching strategy, our DeltaSILAC profiling revealed a global, unexpected delaying effect of many phosphosites on protein turnover. We further found that phosphorylated sites accelerating protein turnover are functionally selected for cell fitness, enriched in Cyclin-dependent kinase substrates, and evolutionarily conserved, whereas the glutamic acids surrounding phosphosites significantly delay protein turnover. Our method represents a generalizable approach and provides a rich resource for prioritizing the effects of phosphorylation sites on protein lifetime in the context of cell signaling and disease biology.

• Klíčová slova
• DeltaSILAC, data-independent acquisition, mass spectrometry, phosphomodiform, phosphorylation, protein lifetime, protein turnover, proteomics, pulse SILAC,
• MeSH
• buněčný cyklus fyziologie   MeSH
• cyklin-dependentní kinasy genetika   metabolismus   MeSH
• fosfoproteiny chemie   metabolismus   MeSH
• fosforylace MeSH
• glutamáty metabolismus   MeSH
• hmotnostní spektrometrie metody   MeSH
• izotopové značení metody   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• peptidy metabolismus   MeSH
• peroxiredoxin VI chemie   metabolismus   MeSH
• proteolýza * MeSH
• proteom genetika   metabolismus   MeSH
• proteomika metody   MeSH
• sekvence aminokyselin MeSH
• sestřihové faktory chemie   metabolismus   MeSH
• signální transdukce genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• cyklin-dependentní kinasy MeSH
• fosfoproteiny MeSH
• glutamáty MeSH
• peptidy MeSH
• peroxiredoxin VI MeSH
• PRDX6 protein, human MeSH Prohlížeč
• proteom MeSH
• sestřihové faktory MeSH
• SF3B1 protein, human MeSH Prohlížeč

Profiling of biological relationships between different molecular layers dissects regulatory mechanisms that ultimately determine cellular function. To thoroughly assess the role of protein post-translational turnover, we devised a strategy combining pulse stable isotope-labeled amino acids in cells (pSILAC), data-independent acquisition mass spectrometry (DIA-MS), and a novel data analysis framework that resolves protein degradation rate on the level of mRNA alternative splicing isoforms and isoform groups. We demonstrated our approach by the genome-wide correlation analysis between mRNA amounts and protein degradation across different strains of HeLa cells that harbor a high grade of gene dosage variation. The dataset revealed that specific biological processes, cellular organelles, spatial compartments of organelles, and individual protein isoforms of the same genes could have distinctive degradation rate. The protein degradation diversity thus dissects the corresponding buffering or concerting protein turnover control across cancer cell lines. The data further indicate that specific mRNA splicing events such as intron retention significantly impact the protein abundance levels. Our findings support the tight association between transcriptome variability and proteostasis and provide a methodological foundation for studying functional protein degradation.

• Klíčová slova
• DIA mass spectrometry, alternative splicing, protein turnover, proteomics, pulsed SILAC,
• MeSH
• alternativní sestřih MeSH
• HeLa buňky MeSH
• hmotnostní spektrometrie MeSH
• izoformy RNA genetika   metabolismus   MeSH
• izotopové značení metody   MeSH
• lidé MeSH
• messenger RNA genetika   metabolismus   MeSH
• protein - isoformy analýza   metabolismus   MeSH
• proteiny analýza   metabolismus   MeSH
• proteolýza MeSH
• proteomika metody   MeSH
• průběh práce MeSH
• regulace genové exprese u nádorů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• izoformy RNA MeSH
• messenger RNA MeSH
• protein - isoformy MeSH
• proteiny MeSH