There is increasing evidence that evolutionary and ecological processes can operate on the same timescale
(i.e., contemporary time). As such, evolution can be sufficiently rapid to affect ecological ...processes such as predation or competition. Thus, evolution can influence population, community, and ecosystem-level dynamics. Indeed, studies have now shown that evolutionary dynamics can alter community structure
and ecosystem function.
In turn, shifts in ecological dynamics driven by evolution might feed back to affect the evolutionary trajectory of individual species.
This feedback loop, where evolutionary and ecological changes reciprocally affect one another, is a central tenet of eco-evolutionary dynamics.
However, most work on such dynamics in natural populations has focused on one-way causal associations between ecology and evolution.
Hence, direct empirical evidence for eco-evolutionary feedback is rare and limited to laboratory or mesocosm experiments.
Here, we show in the wild that eco-evolutionary dynamics in a plant-feeding arthropod community involve a negative feedback loop. Specifically, adaptation in cryptic coloration in a stick-insect species mediates bird predation, with local maladaptation increasing predation. In turn, the abundance of arthropods is reduced by predation. Here, we experimentally manipulate arthropod abundance to show that these changes at the community level feed back to affect the stick-insect evolution. Specifically, low-arthropod abundance increases the strength of selection on crypsis, increasing local adaptation of stick insects in a negative feedback loop. Our results suggest that eco-evolutionary feedbacks are able to stabilize complex systems by preventing consistent directional change and therefore increasing resilience.
Pseudomonas aeruginosa, a major cause of nosocomial and chronic infections, is considered a paradigm of antimicrobial resistance development. However, the evolutionary trajectories of antimicrobial ...resistance and the impact of mutator phenotypes remain mostly unexplored. Therefore, whole-genome sequencing (WGS) was performed in lineages of wild-type and mutator (ΔmutS) strains exposed to increasing concentrations of relevant antipseudomonal agents. WGS provided a privileged perspective of the dramatic effect of mutator phenotypes on the accumulation of random mutations, most of which were transitions, as expected. Moreover, a frameshift mutagenic signature, consistent with error-prone DNA polymerase activity as a consequence of SOS system induction, was also seen. This effect was evidenced for all antibiotics tested, but it was higher for fluoroquinolones than for cephalosporins or carbapenems. Analysis of genotype versus phenotype confirmed expected resistance evolution trajectories but also revealed new pathways. Classical mechanisms included multiple mutations leading to AmpC overexpression (ceftazidime), quinolone resistance-determining region (QRDR) mutations (ciprofloxacin), oprD inactivation (meropenem), and efflux pump overexpression (ciprofloxacin and meropenem). Groundbreaking findings included gain-of-function mutations leading to the structural modification of AmpC (ceftazidime), novel DNA gyrase (GyrA) modification (ciprofloxacin), and the alteration of the β-lactam binding site of penicillin-binding protein 3 (PBP3) (meropenem). A further striking finding was seen in the evolution of meropenem resistance, selecting for specific extremely large (>250 kb) genomic deletions providing a growth advantage in the presence of the antibiotic. Finally, fitness and virulence varied within and across evolved antibiotic-resistant populations, but mutator lineages showed a lower biological cost for some antibiotics.
Phenotypic variation within species can affect the ecological dynamics of populations and communities. Characterizing the genetic variation underlying such effects can help parse the roles of genetic ...evolution and plasticity in 'eco-evolutionary dynamics' and inform how genetic variation may shape patterns of evolution. Here we employ genome-wide association (GWA) methods in Timema cristinae stick insects and their co-occurring arthropod communities to identify genetic variation associated with community-level traits. Previous studies have shown that maladaptation (i.e., imperfect crypsis) of T. cristinae can reduce the abundance and species richness of other arthropods due to an increase in bird predation. Whether genetic variation that is independent from crypsis has similar effects is unknown and was tested here using genome-wide genotyping-by-sequencing data of stick insects, arthropod community information, and GWA mapping with Bayesian sparse linear mixed models. We find associations between genetic variation in stick insects and arthropod community traits. However, these associations disappeared when host-plant traits are accounted for. We thus use path analysis to disentangle interrelationships among stick-insect genetic variation, host-plant traits and community traits. This revealed that host-plant size has large effects on arthropod communities, while genetic variation in stick insects has a smaller, but still significant effect. Our findings demonstrate that: (1) genetic variation in a species can be associated with community-level traits, but that (2) interrelationships among multiple factors may need to be analyzed to disentangle whether such associations represent causal relationships. This work helps to build a framework for genomic studies of eco-evolutionary dynamics.
It has long been recognized that the modification of penicillin-binding proteins (PBPs) to reduce their affinity for beta-lactams is an important mechanism (target modification) by which ...Gram-positive cocci acquire antibiotic resistance. Among Gram-negative rods (GNR), however, this mechanism has been considered unusual, and restricted to clinically irrelevant laboratory mutants for most species. Using as a model Pseudomonas aeruginosa, high up on the list of pathogens causing life-threatening infections in hospitalized patients worldwide, we show that PBPs may also play a major role in beta-lactam resistance in GNR, but through a totally distinct mechanism. Through a detailed genetic investigation, including whole-genome analysis approaches, we demonstrate that high-level (clinical) beta-lactam resistance in vitro, in vivo, and in the clinical setting is driven by the inactivation of the dacB-encoded nonessential PBP4, which behaves as a trap target for beta-lactams. The inactivation of this PBP is shown to determine a highly efficient and complex beta-lactam resistance response, triggering overproduction of the chromosomal beta-lactamase AmpC and the specific activation of the CreBC (BlrAB) two-component regulator, which in turn plays a major role in resistance. These findings are a major step forward in our understanding of beta-lactam resistance biology, and, more importantly, they open up new perspectives on potential antibiotic targets for the treatment of infectious diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Microalgae are complex photosynthetic organisms found in marine and freshwater environments that produce valuable metabolites. Microalgae-derived metabolites have gained remarkable attention in ...different industrial biotechnological processes and pharmaceutical and cosmetic industries due to their multiple properties, including antioxidant, anti-aging, anti-cancer, phycoimmunomodulatory, anti-inflammatory, and antimicrobial activities. These properties are recognized as promising components for state-of-the-art cosmetics and cosmeceutical formulations. Efforts are being made to develop natural, non-toxic, and environmentally friendly products that replace synthetic products. This review summarizes some potential cosmeceutical applications of microalgae-derived biomolecules, their mechanisms of action, and extraction methods.
The photolyase family consists of flavoproteins with enzyme activity able to repair ultraviolet light radiation damage by photoreactivation. DNA damage by the formation of a cyclobutane pyrimidine ...dimer (CPD) and a pyrimidine-pyrimidone (6-4) photoproduct can lead to multiple affections such as cellular apoptosis and mutagenesis that can evolve into skin cancer. The development of integrated applications to prevent the negative effects of prolonged sunlight exposure, usually during outdoor activities, is imperative. This study presents the functions, characteristics, and types of photolyases, their therapeutic and cosmetic applications, and additionally explores some photolyase-producing microorganisms and drug delivery systems.
Background
Nausea and vomiting is a very prevalent condition during pregnancy. Combination of doxylamine and pyridoxine is placed as first-line pharmacological option for its treatment in most ...clinical guidelines. Among different release forms available, Cariban
®
is a fixed-dose combination of doxylamine/pyridoxine 10/10 mg, formulated as modified-release capsules.
Objectives
In the present study, we aimed to characterize the bioavailability performance of Cariban
®
in vitro and in vivo.
Methods
An in vitro dissolution test was performed to evaluate the release profile of Cariban
®
, together with immediate- and delayed-release formulations available on the market. A single-center, single-dose, open-label bioavailability study following Cariban
®
administration in 12 healthy adult female patients was carried out to explore the drug behavior in vivo (protocol NBR-002-13; EUDRA-CT 2013-005422-35). These data were additionally used to perform a computational pharmacokinetic simulation of the posology approved for this drug.
Results
Cariban
®
capsules demonstrate a prolonged-release performance, with an early, gradual, and progressive release of both actives until reaching a complete dissolution after 4–5 h in solution. The pharmacokinetic features of these capsules show that doxylamine and pyridoxine metabolites are early absorbed, being all detectable in plasma within 1 h following oral administration. Computational pharmacokinetic simulation predicts that different posology provides distinct profiles of metabolites in plasma, with 1–1–2 (morning–midafternoon–night) being the one that concentrates higher plasma levels but lower dose dumping for 24 h.
Conclusion
Cariban
®
behaves as a prolonged-release formulation, which correlates with rapid absorption and arising of the actives in the plasma, but also long-lasting and sustained bioavailability, especially when administered following the complete posology. These results would underlie its demonstrated efficacy to relieve nausea and vomiting of pregnancy (NVP) under clinical settings.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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