Plasmids drive genomic diversity in bacteria via horizontal gene transfer 1, 2; nevertheless, explaining their survival in bacterial populations is challenging 3. Theory predicts that irrespective of ...their net fitness effects, plasmids should be lost: when parasitic (costs outweigh benefits), plasmids should decline due to purifying selection 4–6, yet under mutualism (benefits outweigh costs), selection favors the capture of beneficial accessory genes by the chromosome and loss of the costly plasmid backbone 4. While compensatory evolution can enhance plasmid stability within populations 7–15, the propensity for this to occur across the parasitism-mutualism continuum is unknown. We experimentally evolved Pseudomonas fluorescens and its mercury resistance mega-plasmid, pQBR103 16, across an environment-mediated parasitism-mutualism continuum. Compensatory evolution stabilized plasmids by rapidly ameliorating the cost of plasmid carriage in all environments. Genomic analysis revealed that, in both parasitic and mutualistic treatments, evolution repeatedly targeted the gacA/gacS bacterial two-component global regulatory system while leaving the plasmid sequence intact. Deletion of either gacA or gacS was sufficient to completely ameliorate the cost of plasmid carriage. Mutation of gacA/gacS downregulated the expression of ∼17% of chromosomal and plasmid genes and appears to have relieved the translational demand imposed by the plasmid. Chromosomal capture of mercury resistance accompanied by plasmid loss occurred throughout the experiment but very rarely invaded to high frequency, suggesting that rapid compensatory evolution can limit this process. Compensatory evolution can explain the widespread occurrence of plasmids and allows bacteria to retain horizontally acquired plasmids even in environments where their accessory genes are not immediately useful.
•Compensatory evolution stabilized plasmids across a parasitism-mutualism continuum•Selection repeatedly targeted the same genes in independently evolving populations•Mutations in a global regulatory system, gacA/gacS, ameliorated the plasmid cost•Evolved genotypes had reduced the translational demand caused by the plasmid
Harrison et al. show that parallel regulatory mutations of large effect in bacteria rapidly compensated for the cost of plasmid carriage to stabilize both parasitic and mutualistic resistance plasmids. The findings help to explain the widespread occurrence of resistance plasmids and their role in horizontal gene transfer.
Chronic myeloid leukemia (CML) originates in a hematopoietic stem cell (HSC) transformed by the breakpoint cluster region (BCR)-abelson (ABL) oncogene and is effectively treated with tyrosine kinase ...inhibitors (TKIs). TKIs do not eliminate disease-propagating leukemic stem cells (LSCs), suggesting a deeper understanding of niche-dependent regulation of CML LSCs is required to eradicate disease. Cxcl12 is expressed in bone marrow niches and controls HSC maintenance, and here, we show that targeted deletion of Cxcl12 from mesenchymal stromal cells (MSCs) reduces normal HSC numbers but promotes LSC expansion by increasing self-renewing cell divisions, possibly through enhanced Ezh2 activity. In contrast, endothelial cell-specific Cxcl12 deletion decreases LSC proliferation, suggesting niche-specific effects. During CML development, abnormal clusters of colocalized MSCs and LSCs form but disappear upon Cxcl12 deletion. Moreover, MSC-specific deletion of Cxcl12 increases LSC elimination by TKI treatment. These findings highlight a critical role of niche-specific effects of Cxcl12 expression in maintaining quiescence of TKI-resistant LSC populations.
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•CXCL12 deletion from mesenchymal stromal cells (MSCs) expands leukemia stem cells•LSCs undergo increased self-renewing divisions, related to enhanced EZH2 activity•CXCL12 deletion from MSCs increases LSC elimination by TKI treatment•CXCL12+ MSC niches are critical for maintaining quiescent, TKI-resistant LSCs
Leukemia stem cells (LSCs) resist elimination by tyrosine kinase inhibitor (TKI) treatment. Bhatia and colleagues report that CXCL12 deletion from mesenchymal stromal cells (MSCs) reduces LSC colocalization, enhances LSC cycling, and increases LSC elimination by TKI treatment, indicating that CXCL12-expressing MSC niches are critical for maintaining quiescent, TKI-resistant LSCs.
Sediment fluxes in aquatic environments are crucially dependent on bedform dynamics. However, sediment-flux predictions rely almost completely on clean-sand studies, despite most environments being ...composed of mixtures of non-cohesive sands, physically cohesive muds and biologically cohesive extracellular polymeric substances (EPS) generated by microorganisms. EPS associated with surficial biofilms are known to stabilize sediment and increase erosion thresholds. Here we present experimental data showing that the pervasive distribution of low levels of EPS throughout the sediment, rather than the high surficial levels of EPS in biofilms, is the key control on bedform dynamics. The development time for bedforms increases by up to two orders of magnitude for extremely small quantities of pervasively distributed EPS. This effect is far stronger than for physical cohesion, because EPS inhibit sand grains from moving independently. The results highlight that present bedform predictors are overly simplistic, and the associated sediment transport processes require re-assessment for the influence of EPS.
The para‐selective C−H alkylation of aniline derivatives furnished with a pyrimidine auxiliary is herein reported. This reaction is proposed to take place via an N−H‐activated cyclometalate formed in ...situ. Experimental and DFT mechanistic studies elucidate a dual role of the ruthenium catalyst. Here the ruthenium catalyst can undergo cyclometalation by N−H metalation (as opposed to C−H metalation in meta‐selective processes) and form a redox active ruthenium species, to enable site‐selective radical addition at the para position.
Para‐normal activity: The para‐selective C−H alkylation of aniline derivatives is reported. The methodology is proposed to proceed by a dual role ruthenium process: cycloruthenation at N−H and redox radical generation. This strategy leads to para‐selective alkylations using pyrimidine and quinazoline auxiliaries.
The selection of paleointensity data is a challenging, but essential step for establishing data reliability. There is, however, no consensus as to how best to quantify paleointensity data and which ...data selection processes are most effective. To address these issues, we begin to lay the foundations for a more unified and theoretically justified approach to the selection of paleointensity data. We present a new compilation of standard definitions for paleointensity statistics to help remove ambiguities in their calculation. We also compile the largest‐to‐date data set of raw paleointensity data from historical locations and laboratory control experiments with which to test the effectiveness of commonly used sets of selection criteria. Although most currently used criteria are capable of increasing the proportion of accurate results accepted, criteria that are better at excluding inaccurate results tend to perform poorly at including accurate results and vice versa. In the extreme case, one widely used set of criteria, which is used by default in the ThellierTool software (v4.22), excludes so many accurate results that it is often statistically indistinguishable from randomly selecting data. We demonstrate that, when modified according to recent single domain paleointensity predictions, criteria sets that are no better than a random selector can produce statistically significant increases in the acceptance of accurate results and represent effective selection criteria. The use of such theoretically derived modifications places the selection of paleointensity data on a more justifiable theoretical foundation and we encourage the use of the modified criteria over their original forms.
Key Points
Standard definitions for paleointensity statistics are proposed
A large paleointensity meta‐analysis is conducted to investigate data selection
Modifications based on SD predictions improve the effectiveness of selection
Pineapple (Ananas comosus (L.) Merr.) is the most economically valuable crop possessing crassulacean acid metabolism (CAM), a photosynthetic carbon assimilation pathway with high water-use ...efficiency, and the second most important tropical fruit. We sequenced the genomes of pineapple varieties F153 and MD2 and a wild pineapple relative, Ananas bracteatus accession CB5. The pineapple genome has one fewer ancient whole-genome duplication event than sequenced grass genomes and a conserved karyotype with seven chromosomes from before the ρ duplication event. The pineapple lineage has transitioned from C3 photosynthesis to CAM, with CAM-related genes exhibiting a diel expression pattern in photosynthetic tissues. CAM pathway genes were enriched with cis-regulatory elements associated with the regulation of circadian clock genes, providing the first cis-regulatory link between CAM and circadian clock regulation. Pineapple CAM photosynthesis evolved by the reconfiguration of pathways in C3 plants, through the regulatory neofunctionalization of preexisting genes and not through the acquisition of neofunctionalized genes via whole-genome or tandem gene duplication.
Biologically active, fine‐grained sediment forms abundant sedimentary deposits on Earth's surface, and mixed mud‐sand dominates many coasts, deltas, and estuaries. Our predictions of sediment ...transport and bed roughness in these environments presently rely on empirically based bed form predictors that are based exclusively on biologically inactive cohesionless silt, sand, and gravel. This approach underpins many paleoenvironmental reconstructions of sedimentary successions, which rely on analysis of cross‐stratification and bounding surfaces produced by migrating bed forms. Here we present controlled laboratory experiments that identify and quantify the influence of physical and biological cohesion on equilibrium bed form morphology. The results show the profound influence of biological cohesion on bed form size and identify how cohesive bonding mechanisms in different sediment mixtures govern the relationships. The findings highlight that existing bed form predictors require reformulation for combined biophysical cohesive effects in order to improve morphodynamic model predictions and to enhance the interpretations of these environments in the geological record.
Key Points
Subaqueous bed form dimensions are controlled more by biological than physical cohesion
Existing predictors require reformulation for combined biophysical cohesive effects
Small amounts of substrate biological cohesion act to reduce bed roughness 2 orders of magnitude
Intertidal systems are complex and dynamic environments with many interacting factors influencing biochemical characteristics and microbial communities. One key factor are the actions of resident ...fauna, many of which are regarded as ecosystem engineers because of their bioturbation, bioirrigation and sediment stabilising activities. The purpose of this investigation was to elucidate the evolutionary implications of the ecosystem engineering process by identifying, if any, aspects that act as selection pressures upon microbial communities. A mesocosm study was performed using the well characterised intertidal ecosystem engineers Corophium volutator, Hediste diversicolor, and microphytobenthos, in addition to manual turbation of sediments to compare effects of bioturbation, bioirrigation and stabilisation. A range of sediment functions and biogeochemical gradients were measured in conjunction with 16S rRNA sequencing and diatom taxonomy, with downstream bacterial metagenome function prediction, to identify selection pressures that incited change to microbial community composition and function. Bacterial communities were predominantly Proteobacteria, with the relative abundance of Bacteroidetes, Alphaproteobacteria and Verrucomicrobia being partially displaced by Deltaproteobacteria, Acidobacteria and Chloroflexi as dissolved oxygen concentration and redox potential decreased. Bacterial community composition was driven strongly by biogeochemistry; surface communities were affected by a combination of sediment functions and overlying water turbidity, and subsurface communities by biogeochemical gradients driven by sediment reworking. Diatom communities were dominated by Nitzschia laevis and Achnanthes sp., and assemblage composition was influenced by overlying water turbidity (manual or biogenic) rather than direct infaunal influences such as grazing.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A catalytic meta-selective C-H functionalization of 2-phenylpyridines using a range of tertiary halides is described. The protocol is simple to perform and uses commercially available reagents to ...construct challenging quaternary carbon centres in a regioselective manner. Preliminary studies suggest the C-H functionalization proceeds through a radical process directed via a remote σ-activation.
Summary Highly virulent strains of Clostridium difficile have emerged since 2003, causing large outbreaks of severe, often fatal, colitis in North America and Europe. In 2008–10, virulent strains ...spread between continents, with the first reported cases of fluoroquinolone-resistant C difficile PCR ribotype 027 in three Asia-Pacific countries and Central America. We present a risk assessment framework for assessing risks of further worldwide spread of this pathogen. This framework first requires identification of potential vehicles of introduction, including international transfers of hospital patients, international tourism and migration, and trade in livestock, associated commodities, and foodstuffs. It then calls for assessment of the risks of pathogen release, of exposure of individuals if release happens, and of resulting outbreaks. Health departments in countries unaffected by outbreaks should assess the risk of introduction or reintroduction of C difficile PCR ribotype 027 using a structured risk-assessment approach.
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