| 1. |
- Joers, Arvi, et al.
(författare)
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Muropeptides Stimulate Growth Resumption from Stationary Phase in Escherichia coli
- 2019
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- When nutrients run out, bacteria enter a dormant metabolic state. This low or undetectable metabolic activity helps bacteria to preserve their scant reserves for the future needs, yet it also diminishes their ability to scan the environment for new growth-promoting substrates. However, neighboring microbial growth is a reliable indicator of a favorable environment and can thus serve as a cue for exiting dormancy. Here we report that for Escherichia coli and Pseudomonas aeruginosa this cue is provided by the basic peptidoglycan unit (i.e. muropeptide). We show that several forms of muropeptides from a variety of bacterial species can stimulate growth resumption of dormant cells and the sugar-peptide bond is crucial for this activity. These results, together with previous research that identifies muropeptides as a germination signal for bacterial spores, and their detection by mammalian immune cells, show that muropeptides are a universal cue for bacterial growth.
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| 2. |
- Karmin, Monika, et al.
(författare)
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A recent bottleneck of Y chromosome diversity coincides with a global change in culture.
- 2015
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 25:4
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Tidskriftsartikel (refereegranskat)abstract
- It is commonly thought that human genetic diversity in non-African populations was shaped primarily by an out-of-Africa dispersal 50-100 thousand yr ago (kya). Here, we present a study of 456 geographically diverse high-coverage Y chromosome sequences, including 299 newly reported samples. Applying ancient DNA calibration, we date the Y-chromosomal most recent common ancestor (MRCA) in Africa at 254 (95% CI 192-307) kya and detect a cluster of major non-African founder haplogroups in a narrow time interval at 47-52 kya, consistent with a rapid initial colonization model of Eurasia and Oceania after the out-of-Africa bottleneck. In contrast to demographic reconstructions based on mtDNA, we infer a second strong bottleneck in Y-chromosome lineages dating to the last 10 ky. We hypothesize that this bottleneck is caused by cultural changes affecting variance of reproductive success among males.
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| 3. |
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| 4. |
- Saag, Lehti, et al.
(författare)
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The Arrival of Siberian Ancestry Connecting the Eastern Baltic to Uralic Speakers further East
- 2019
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 29:10, s. 1701-
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we compare the genetic ancestry of individuals from two as yet genetically unstudied cultural traditions in Estonia in the context of available modern and ancient datasets: 15 from the Late Bronze Age stone-cist graves (1200-400 BC) (EstBA) and 6 from the Pre-Roman Iron Age tarand cemeteries (800/500 BC-50 AD) (EstIA). We also included 5 Pre-Roman to Roman Iron Age Ingrian (500 BC450 AD) (IngIA) and 7 Middle Age Estonian (1200-1600 AD) (EstMA) individuals to build a dataset for studying the demographic history of the northern parts of the Eastern Baltic from the earliest layer of Mesolithic to modern times. Our findings are consistent with EstBA receiving gene flow from regions with strong Western hunter-gatherer (WHG) affinities and EstIA from populations related to modern Siberians. The latter inference is in accordance with Y chromosome (chrY) distributions in present day populations of the Eastern Baltic, as well as patterns of autosomal variation in the majority of the westernmost Uralic speakers [1-5]. This ancestry reached the coasts of the Baltic Sea no later than the mid-first millennium BC; i.e., in the same time window as the diversification of west Uralic (Finnic) languages [6]. Furthermore, phenotypic traits often associated with modern Northern Europeans, like light eyes, hair, and skin, as well as lactose tolerance, can be traced back to the Bronze Age in the Eastern Baltic.
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| 5. |
- Sothiselvam, Shanmugapriya, et al.
(författare)
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Macrolide antibiotics allosterically predispose the ribosome for translation arrest
- 2014
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 111:27, s. 9804-9809
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Tidskriftsartikel (refereegranskat)abstract
- Translation arrest directed by nascent peptides and small cofactors controls expression of important bacterial and eukaryotic genes, including antibiotic resistance genes, activated by binding of macrolide drugs to the ribosome. Previous studies suggested that specific interactions between the nascent peptide and the antibiotic in the ribosomal exit tunnel play a central role in triggering ribosome stalling. However, here we show that macrolides arrest translation of the truncated ErmDL regulatory peptide when the nascent chain is only three amino acids and therefore is too short to be juxtaposed with the antibiotic. Biochemical probing and molecular dynamics simulations of erythromycin-bound ribosomes showed that the antibiotic in the tunnel allosterically alters the properties of the catalytic center, thereby predisposing the ribosome for halting translation of specific sequences. Our findings offer a new view on the role of small cofactors in the mechanism of translation arrest and reveal an allosteric link between the tunnel and the catalytic center of the ribosome.
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| 6. |
- Tasa, Tonis, et al.
(författare)
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Genetic variation in the Estonian population : pharmacogenomics study of adverse drug effects using electronic health records
- 2019
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Ingår i: European Journal of Human Genetics. - : NATURE PUBLISHING GROUP. - 1018-4813 .- 1476-5438. ; 27:3, s. 442-454
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Tidskriftsartikel (refereegranskat)abstract
- Pharmacogenomics aims to tailor pharmacological treatment to each individual by considering associations between genetic polymorphisms and adverse drug effects (ADEs). With technological advances, pharmacogenomic research has evolved from candidate gene analyses to genome-wide association studies. Here, we integrate deep whole-genome sequencing (WGS) information with drug prescription and ADE data from Estonian electronic health record (EHR) databases to evaluate genome- and pharmacome-wide associations on an unprecedented scale. We leveraged WGS data of 2240 Estonian Biobank participants and imputed all single-nucleotide variants (SNVs) with allele counts over 2 for 13,986 genotyped participants. Overall, we identified 41 (10 novel) loss-of-function and 567 (134 novel) missense variants in 64 very important pharmacogenes. The majority of the detected variants were very rare with frequencies below 0.05%, and 6 of the novel lossof-function and 99 of the missense variants were only detected as single alleles (allele count = 1). We also validated documented pharmacogenetic associations and detected new independent variants in known gene-drug pairs. Specifically, we found that CTNNA3 was associated with myositis and myopathies among individuals taking nonsteroidal anti-inflammatory oxicams and replicated this finding in an extended cohort of 706 individuals. These findings illustrate that population-based WGS-coupled EHRs are a useful tool for biomarker discovery.
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