Voriconazole and fluconazole increase the exposure to oral diazepam

Conclusion Both voriconazole and fluconazole considerably increase the exposure to diazepam. Recurrent administration of diazepam increases the risk of clinically significant interactions during voriconazole or fluconazole treatment, because the elimination of diazepam is impaired significantly

Streamlined and Abundant Bacterioplankton Thrive in Functional Cohorts

While fastidious microbes can be abundant and ubiquitous in their natural communities, many fail to grow axenically in laboratories due to auxotrophies or other dependencies. To overcome auxotrophies, these microbes rely on their surrounding cohort. A cohort may consist of kin (ecotypes) or more distantly related organisms (community) with the cooperation being reciprocal or nonreciprocal and expensive (Black Queen hypothesis) or costless (by-product). These metabolic partnerships (whether at single species population or community level) enable dominance by and coexistence of these lineages in nature. Here we examine the relevance of these cooperation models to explain the abundance and ubiquity of the dominant fastidious bacterioplankton of a dimictic mesotrophic freshwater lake. Using both culture-dependent (dilution mixed cultures) and culture-independent (small subunit [SSU] rRNA gene time series and environmental metagenomics) methods, we independently identified the primary cohorts of actinobacterial genera "Candidatus Planktophila" (acI-A) and "Candidatus Nanopelagicus" (acI-B) and the proteobacterial genus "Candidatus Fonsibacter" (LD12). While "Ca. Planktophila" and "Ca. Fonsibacter" had no correlation in their natural habitat, they have the potential to be complementary in laboratory settings. We also investigated the bifunctional catalase-peroxidase enzyme KatG (a common good which "Ca. Planktophila" is dependent upon) and its most likely providers in the lake. Further, we found that while ecotype and community cooperation combined may explain "Ca. Planktophila" population abundance, the success of "Ca. Nanopelagicus" and "Ca. Fonsibacter" is better explained as a community by-product. Ecotype differentiation of "Ca. Fonsibacter" as a means of escaping predation was supported but not for overcoming auxotrophies.IMPORTANCE This study examines evolutionary and ecological relationships of three of the most ubiquitous and abundant freshwater bacterial genera: "Ca. Planktophila" (acI-A), "Ca. Nanopelagicus" (acI-B), and "Ca. Fonsibacter" (LD12). Due to high abundance, these genera might have a significant influence on nutrient cycling in freshwaters worldwide, and this study adds a layer of understanding to how seemingly competing clades of bacteria can coexist by having different cooperation strategies. Our synthesis ties together network and ecological theory with empirical evidence and lays out a framework for how the functioning of populations within complex microbial communities can be studied

The influence of light and Water mass on bacterial population dynamics in the Amundsen Sea Polynya

Abstract Despite being perpetually cold, seasonally ice-covered and dark, the coastal Southern Ocean is highly productive and harbors a diverse microbiota. During the austral summer, ice-free coastal patches (or polynyas) form, exposing pelagic organisms to sunlight, triggering intense phytoplankton blooms. This strong seasonality is likely to influence bacterioplankton community composition (BCC). For the most part, we do not fully understand the environmental drivers controlling high-latitude BCC and the biogeochemical cycles they mediate. In this study, the Amundsen Sea Polynya was used as a model system to investigate important environmental factors that shape the coastal Southern Ocean microbiota. Population dynamics in terms of occurrence and activity of abundant taxa was studied in both environmental samples and microcosm experiments by using 454 pyrosequencing of 16S rRNA genes. We found that the BCC in the photic epipelagic zone had low richness, with dominant bacterial populations being related to taxa known to benefit from high organic carbon and nutrient loads (copiotrophs). In contrast, the BCC in deeper mesopelagic water masses had higher richness, featuring taxa known to benefit from low organic carbon and nutrient loads (oligotrophs). Incubation experiments indicated that direct impacts of light and competition for organic nutrients are two important factors shaping BCC in the Amundsen Sea Polynya

Summer comes to the Southern Ocean: how phytoplankton shape bacterioplankton communities far into the deep dark sea

18 pages, 6 figures, 1 table, supporting information https://doi.org/10.1002/ecs2.2641During austral spring and summer, the coastal Antarctic experiences a sharp increase in primary production and a steepening of biotic and abiotic gradients that result from increased solar radiation and retreating sea ice. In one of the largest seasonally ice-free regions, the Amundsen Sea Polynya, pelagic samples were collected from 15 sites during a massive Phaeocystis antarctica bloom in 2010/2011. Along with a suite of other biotic and abiotic measurements, bacterioplankton were collected and analyzed for community structure by pyrosequencing of the 16S rRNA gene. The aims were to identify patterns in diversity and composition of heterotrophic bacterioplankton and to test mechanistic hypotheses for explaining these differences along variations in depth, water mass, phytoplankton biomass, and organic and inorganic nutrients. The overall goal was to clarify the relationship between primary producers and bacterioplankton community structure in the Southern Ocean. Results suggested that both epipelagic and mesopelagic bacterioplankton communities were structured by phytoplankton blooming in the euphotic zone. As chlorophyll a (chl-a) increased in surface waters, the abundance of surface bacterioplankton increased, but their diversity decreased. Similarity in bacterioplankton community composition between surface-water sites increased as the bloom progressed, suggesting that algal blooms may homogenize surface-water bacterioplankton communities at larger spatial scales. Below the euphotic zone, the opposite relationship was found. Mesopelagic bacterioplankton diversity increased with increasing chl-a in the overlying surface waters. This shift may be promoted by several factors including local increase in organic and inorganic nutrients from particles sinking out of the euphotic zone, an increase in niche differentiation associated with the particle flux, interactions with deep-dwelling macrozooplankton, and release from competition with primary producers. Additional multivariate analyses of bacterioplankton community structure and nutrient concentrations revealed distinct depth horizons, with bacterioplankton communities having maximum alpha and beta diversity just below the euphotic zone, while nutrient composition gradually homogenized with increasing depth. Our results provide evidence for bloom-driven (bottom-up) control of bacterioplankton community diversity in the coastal Southern Ocean and suggest mechanisms whereby surface processes can shape the diversity of bacterioplankton communities at great depthThe study was funded by the Swedish Research Council (grants to SB and LR) and the U.S. National Science Foundation through the ASPIRE project (ANT‐0839069

The Amundsen Sea Polynya International Research Expedition (ASPIRE)

In search of an explanation for some of the greenest waters ever seen in coastal Antarctica and their possible link to some of the fastest melting glaciers and declining summer sea ice, the Amundsen Sea Polynya International Research Expedition (ASPIRE) challenged the capabilities of the US Antarctic Program and RVIB Nathaniel B. Palmer during Austral summer 2010–2011. We were well rewarded by both an extraordinary research platform and a truly remarkable oceanic setting. Here we provide further insights into the key questions that motivated our sampling approach during ASPIRE and present some preliminary findings, while highlighting the value of the Palmer for accomplishing complex, multifaceted oceanographic research in such a challenging environment

Deltaproteobacteria and Spirochaetes-Like Bacteria Are Abundant Putative Mercury Methylators in Oxygen-Deficient Water and Marine Particles in the Baltic Sea

Methylmercury (MeHg), a neurotoxic compound biomagnifying in aquatic food webs, can be a threat to human health via fish consumption. However, the composition and distribution of the microbial communities mediating the methylation of mercury (Hg) to MeHg in marine systems remain largely unknown. In order to fill this knowledge gap, we used the Baltic Sea Reference Metagenome (BARM) dataset to study the abundance and distribution of the genes involved in Hg methylation (thehgcABgene cluster). We determined the relative abundance of thehgcABgenes and their taxonomic identity in 81 brackish metagenomes that cover spatial, seasonal and redox variability in the Baltic Sea water column. ThehgcABgenes were predominantly detected in anoxic water, but somehgcABgenes were also detected in hypoxic and normoxic waters. Phylogenetic analysis identified putative Hg methylators within Deltaproteobacteria, in oxygen-deficient water layers, but also Spirochaetes-like and Kiritimatiellaeota-like bacteria. Higher relative quantities ofhgcABgenes were found in metagenomes from marine particles compared to free-living communities in anoxic water, suggesting that such particles are hotspot habitats for Hg methylators in oxygen-depleted seawater. Altogether, our work unveils the diversity of the microorganisms with the potential to mediate MeHg production in the Baltic Sea and pinpoint the important ecological niches for these microorganisms within the marine water column

MOVING TOWARD GENETIC PROFILING IN PATIENT CARE: THE SCOPE AND RATIONALE OF PHARMACOGENETIC/ECOGENETIC INVESTIGATION

This paper is available online at http://dmd.aspetjournals.org The topic of genetic profiling in patient care was recently reviewed in Nature Biotechnology under the title "Laying the foundations for personalised medicines" Genetic variability and selection directed toward the characters of the individuals are considered to be the fundament of the evolution and adaptation of living organisms to all environments where they are able to exist. The interplay between genetic constitution and other factors has consistently been emphasized. The true meaning of "heritage" is sometimes misunderstood. The fact that a character is inherited or has a genetic predisposition does not mean that it has to penetrate into the phenotype of the next generation or that parents necessarily need to share a quality that is obvious in their children. Many characters may be conceived as continuous variables, and among these are diverse physical and intellectual capacities, talents for art, etc. However, they all go back to the genetic code and will only appear as continuous or even gaussian variables if a large enough number of factors is involved in their control and a large enough number of individuals is studied. When investigated in detail, however, most characters will show skewness or separation into different modes. This can be explained by the influence of particularly strong factors such as monogenic or oligogenic coding systems or the influence of singular environmental factors. Many examples of characteristics such as eye color, blood groups, tissue antigens, etc. show discrete variation into separate groups. This is also true for certain drug-metabolizing enzymes. An early observation was that isoniazid might be slowly or rapidly acetylated The most important drug-metabolizing enzyme family is the cytochrome P450 system. It comprises several enzymes that show distinct but partially overlapping substrate specificity Tricyclic antidepressants were early found to display vast interindividual variability in steady-state plasma concentrations. The Debrisoquine/Sparteine Hydroxylation Polymorphism (CYP2D6) Debrisoquine was launched as an antihypertensive agent but is no longer on the market. It was found to induce orthostatic hypotension in a small percentage of healthy volunteers who took the drug for investigational purposes. The reason for the exaggerated effect in these subjects was found to be the lack of an enzyme almost exclusively responsible for the metabolic elimination of debrisoquine, and the affected subjects were classified as poor metabolizers of debrisoquine The character of being a poor (PM) or an extensive metabolizer (EM) of debrisoquine is controlled as an autosomal, recessive monogenic trait with the PM phenotype being the recessive alternative. The genetic heritability of the debrisoquine hydroxylation phenotype is very high (79%), while only 6% of all variability of the debrisoquine metabolic ratio could be ascribed to environmental or cultural factors (Steiner et al.

Oxygen-deficient water zones in the Baltic Sea promote uncharacterized Hg methylating microorganisms in underlying sediments

Human-induced expansion of oxygen-deficient zones can have dramatic impacts on marine systems and its resident biota. One example is the formation of the potent neurotoxic methylmercury (MeHg) that is mediated by microbial methylation of inorganic divalent Hg (Hg-II) under oxygen-deficient conditions. A negative consequence of the expansion of oxygen-deficient zones could be an increase in MeHg production due to shifts in microbial communities in favor of microorganisms methylating Hg. There is, however, limited knowledge about Hg-methylating microbes, i.e., those carrying hgc genes critical for mediating the process, from marine sediments. Here, we aim to study the presence of hgc genes and transcripts in metagenomes and metatranscriptomes from four surface sediments with contrasting concentrations of oxygen and sulfide in the Baltic Sea. We show that potential Hg methylators differed among sediments depending on redox conditions. Sediments with an oxygenated surface featured hgc-like genes and transcripts predominantly associated with uncultured Desulfobacterota (OalgD group) and Desulfobacterales (including Desulfobacula sp.) while sediments with a hypoxic-anoxic surface included hgc-carrying Verrucomicrobia, unclassified Desulfobacterales, Desulfatiglandales, and uncharacterized microbes. Our data suggest that the expansion of oxygen-deficient zones in marine systems may lead to a compositional change of Hg-methylating microbial groups in the sediments, where Hg methylators whose metabolism and biology have not yet been characterized will be promoted and expand

The under-ice microbiome of seasonally frozen lakes

Compared to the well-studied open water of the “growing” season, under-ice conditions in lakes are characterized by low and rather constant temperature, slow water movements, limited light availability, and reduced exchange with the surrounding landscape. These conditions interact with ice-cover duration to shape microbial processes in temperate lakes and ultimately influence the phenology of community and ecosystem processes. We review the current knowledge on microorganisms in seasonally frozen lakes. Specifically, we highlight how under-ice conditions alter lake physics and the ways that this can affect the distribution and metabolism of auto- and heterotrophic microorganisms. We identify functional traits that we hypothesize are important for understanding under-ice dynamics and discuss how these traits influence species interactions. As ice coverage duration has already been seen to reduce as air temperatures have warmed, the dynamics of the under-ice microbiome are important for understanding and predicting the dynamics and functioning of seasonally frozen lakes in the near future