Visible-Light Activation of Diorganyl Bis(pyridylimino) Isoindolide Aluminum(III) Complexes and Their Organometallic Radical Reactivity.

We report on the synthesis and characterization of a series of (mostly) air-stable diorganyl bis(pyridylimino) isoindolide (BPI) aluminum complexes and their chemistry upon visible-light excitation. The redox non-innocent BPI pincer ligand allows for efficient charge transfer homolytic processes of the title compounds. This makes them a universal platform for the generation of carbon-centered radicals. The photo-induced homolytic cleavage of the Al-C bonds was investigated by means of stationary and transient UV/Vis spectroscopy, spin trapping experiments, as well as EPR and NMR spectroscopy. The experimental findings were supported by quantum chemical calculations. Reactivity studies enabled the utilization of the aluminum complexes as reactants in tin-free Giese-type reactions and carbonyl alkylations under ambient conditions, which both indicated radical-polar crossover behavior. A deeper understanding of the physical fundamentals and photochemical process was provided, furnishing in turn a new strategy to control the reactivity of bench-stable aluminum organometallics.

Landscape of global urban environmental resistome and its association with local socioeconomic and medical status.

Antimicrobial resistance (AMR) poses a critical threat to global health and development, with environmental factors-particularly in urban areas-contributing significantly to the spread of antibiotic resistance genes (ARGs). However, most research to date has been conducted at a local level, leaving significant gaps in our understanding of the global status of antibiotic resistance in urban environments. To address this issue, we thoroughly analyzed a total of 86,213 ARGs detected within 4,728 metagenome samples, which were collected by the MetaSUB International Consortium involving diverse urban environments in 60 cities of 27 countries, utilizing a deep-learning based methodology. Our findings demonstrated the strong geographical specificity of urban environmental resistome, and their correlation with various local socioeconomic and medical conditions. We also identified distinctive evolutionary patterns of ARG-related biosynthetic gene clusters (BGCs) across different countries, and discovered that the urban environment represents a rich source of novel antibiotics. Our study provides a comprehensive overview of the global urban environmental resistome, and fills a significant gap in our knowledge of large-scale urban antibiotic resistome analysis.

Nasal Breathing Assessment Using Computational Fluid Dynamics: An Update from the Rhinologic Perspective.

An objective assessment of nasal breathing is currently insufficiently achievable. The application of computational fluid dynamics for this purpose is increasingly gaining attention. However, the suggested specific frameworks can differ considerably. To the best of our knowledge, there is not yet a widely accepted clinical usage of computational fluid dynamics. In this article, selected aspects are addressed that might be crucial for future development and possible implementation of computational fluid dynamics in rhinology.

Towards the discovery of novel molecular clocks in Prokaryotes.

Diel cycle is of enormous biological importance as it imposes daily oscillation in environmental conditions, which temporally structures most ecosystems. Organisms developed biological time-keeping mechanisms - circadian clocks - that provide a significant fitness advantage over competitors by optimising the synchronisation of their biological activities. While circadian clocks are ubiquitous in Eukaryotes, they are so far only characterised in Cyanobacteria within Prokaryotes. However, growing evidence suggests that circadian clocks are widespread in the bacterial and archaeal domains. As Prokaryotes are at the heart of crucial environmental processes and are essential to human health, unravelling their time-keeping systems provides numerous applications in medical research, environmental sciences, and biotechnology. In this review, we elaborate on how novel circadian clocks in Prokaryotes offer research and development perspectives. We compare and contrast the different circadian systems in Cyanobacteria and discuss about their evolution and taxonomic distribution. We necessarily provide an updated phylogenetic analysis of bacterial and archaeal species that harbour homologs of the main cyanobacterial clock components. Finally, we elaborate on new potential clock-controlled microorganisms that represent opportunities of ecological and industrial relevance in prokaryotic groups such as anoxygenic photosynthetic bacteria, methanogenic archaea, methanotrophs or sulphate-reducing bacteria.

The Roles of Secreted Wnt Ligands in Cancer.

Wnt ligands are secreted signaling proteins that display a wide range of biological effects. They play key roles in stimulating Wnt signaling pathways to facilitate processes such as tissue homeostasis and regeneration. Dysregulation of Wnt signaling is a hallmark of many cancers and genetic alterations in various Wnt signaling components, which result in ligand-independent or ligand-dependent hyperactivation of the pathway that have been identified. Recently, research is focusing on the impact of Wnt signaling on the interaction between tumor cells and their micro-environment. This Wnt-mediated crosstalk can act either in a tumor promoting or suppressing fashion. In this review, we comprehensively outline the function of Wnt ligands in different tumor entities and their impact on key phenotypes, including cancer stemness, drug resistance, metastasis, and immune evasion. Lastly, we elaborate approaches to target Wnt ligands in cancer therapy.

Trait-trait relationships and tradeoffs vary with genome size in prokaryotes.

We report genomic traits that have been associated with the life history of prokaryotes and highlight conflicting findings concerning earlier observed trait correlations and tradeoffs. In order to address possible explanations for these contradictions we examined trait-trait variations of 11 genomic traits from ~18,000 sequenced genomes. The studied trait-trait variations suggested: (i) the predominance of two resistance and resilience-related orthogonal axes and (ii) at least in free living species with large effective population sizes whose evolution is little affected by genetic drift an overlap between a resilience axis and an oligotrophic-copiotrophic axis. These findings imply that resistance associated traits of prokaryotes are globally decoupled from resilience related traits and in the case of free-living communities also from traits associated with resource availability. However, further inspection of pairwise scatterplots showed that resistance and resilience traits tended to be positively related for genomes up to roughly five million base pairs and negatively for larger genomes. Genome size distributions differ across habitats and our findings therefore point to habitat dependent tradeoffs between resistance and resilience. This in turn may preclude a globally consistent assignment of prokaryote genomic traits to the competitor - stress-tolerator - ruderal (CSR) schema that sorts species depending on their location along disturbance and productivity gradients into three ecological strategies and may serve as an explanation for conflicting findings from earlier studies. All reviewed genomic traits featured significant phylogenetic signals and we propose that our trait table can be applied to extrapolate genomic traits from taxonomic marker genes. This will enable to empirically evaluate the assembly of these genomic traits in prokaryotic communities from different habitats and under different productivity and disturbance scenarios as predicted via the resistance-resilience framework formulated here.

Intrinsic nonlinear dynamics drive single-species systems.

The importance of oscillations and deterministic chaos in natural biological systems has been discussed for several decades and was originally based on discrete-time population growth models (May 1974). Recently, all types of nonlinear dynamics were shown for experimental communities where several species interact. Yet, there are no data exhibiting the whole range of nonlinear dynamics for single-species systems without trophic interactions. Up until now, ecological experiments and models ignored the intracellular dimension, which includes multiple nonlinear processes even within one cell type. Here, we show that dynamics of single-species systems of protists in continuous experimental chemostat systems and corresponding continuous-time models reveal typical characteristics of nonlinear dynamics and even deterministic chaos, a very rare discovery. An automatic cell registration enabled a continuous and undisturbed analysis of dynamic behavior with a high temporal resolution. Our simple and general model considering the cell cycle exhibits a remarkable spectrum of dynamic behavior. Chaos-like dynamics were shown in continuous single-species populations in experimental and modeling data on the level of a single type of cells without any external forcing. This study demonstrates how complex processes occurring in single cells influence dynamics on the population level. Nonlinearity should be considered as an important phenomenon in cell biology and single-species dynamics and also, for the maintenance of high biodiversity in nature, a prerequisite for nature conservation.

A history of the MetaSUB consortium: Tracking urban microbes around the globe.

The MetaSUB Consortium, founded in 2015, is a global consortium with an interdisciplinary team of clinicians, scientists, bioinformaticians, engineers, and designers, with members from more than 100 countries across the globe. This network has continually collected samples from urban and rural sites including subways and transit systems, sewage systems, hospitals, and other environmental sampling. These collections have been ongoing since 2015 and have continued when possible, even throughout the COVID-19 pandemic. The consortium has optimized their workflow for the collection, isolation, and sequencing of DNA and RNA collected from these various sites and processing them for metagenomics analysis, including the identification of SARS-CoV-2 and its variants. Here, the Consortium describes its foundations, and its ongoing work to expand on this network and to focus its scope on the mapping, annotation, and prediction of emerging pathogens, mapping microbial evolution and antibiotic resistance, and the discovery of novel organisms and biosynthetic gene clusters.

Targeting euchromatic histone lysine methyltransferases sensitizes colorectal cancer to histone deacetylase inhibitors.

Epigenetic dysregulation is an important feature of colorectal cancer (CRC). Combining epigenetic drugs with other antineoplastic agents is a promising treatment strategy for advanced cancers. Here, we exploited the concept of synthetic lethality to identify epigenetic targets that act synergistically with histone deacetylase (HDAC) inhibitors to reduce the growth of CRC. We applied a pooled CRISPR-Cas9 screen using a custom sgRNA library directed against 614 epigenetic regulators and discovered that knockout of the euchromatic histone-lysine N-methyltransferases 1 and 2 (EHMT1/2) strongly enhanced the antiproliferative effect of clinically used HDAC inhibitors. Using tissue microarrays from 1066 CRC samples with different tumor stages, we showed that low EHMT2 protein expression is predominantly found in advanced CRC and associated with poor clinical outcome. Cotargeting of HDAC and EHMT1/2 with specific small molecule inhibitors synergistically reduced proliferation of CRC cell lines. Mechanistically, we used a high-throughput Western blot assay to demonstrate that both inhibitors elicited distinct cellular mechanisms to reduce tumor growth, including cell cycle arrest and modulation of autophagy. On the epigenetic level, the compounds increased H3K9 acetylation and reduced H3K9 dimethylation. Finally, we used a panel of patient-derived CRC organoids to show that HDAC and EHMT1/2 inhibition synergistically reduced tumor viability in advanced models of CRC.

Cross-Talk between p53 and Wnt Signaling in Cancer.

Targeting cancer hallmarks is a cardinal strategy to improve antineoplastic treatment. However, cross-talk between signaling pathways and key oncogenic processes frequently convey resistance to targeted therapies. The p53 and Wnt pathway play vital roles for the biology of many tumors, as they are critically involved in cancer onset and progression. Over recent decades, a high level of interaction between the two pathways has been revealed. Here, we provide a comprehensive overview of molecular interactions between the p53 and Wnt pathway discovered in cancer, including complex feedback loops and reciprocal transactivation. The mutational landscape of genes associated with p53 and Wnt signaling is described, including mutual exclusive and co-occurring genetic alterations. Finally, we summarize the functional consequences of this cross-talk for cancer phenotypes, such as invasiveness, metastasis or drug resistance, and discuss potential strategies to pharmacologically target the p53-Wnt interaction.

Annotating unknown species of urban microorganisms on a global scale unveils novel functional diversity and local environment association.

In urban ecosystems, microbes play a key role in maintaining major ecological functions that directly support human health and city life. However, the knowledge about the species composition and functions involved in urban environments is still limited, which is largely due to the lack of reference genomes in metagenomic studies comprises more than half of unclassified reads. Here we uncovered 732 novel bacterial species from 4728 samples collected from various common surface with the matching materials in the mass transit system across 60 cities by the MetaSUB Consortium. The number of novel species is significantly and positively correlated with the city population, and more novel species can be identified in the skin-associated samples. The in-depth analysis of the new gene catalog showed that the functional terms have a significant geographical distinguishability. Moreover, we revealed that more biosynthetic gene clusters (BGCs) can be found in novel species. The co-occurrence relationship between BGCs and genera and the geographical specificity of BGCs can also provide us more information for the synthesis pathways of natural products. Expanded the known urban microbiome diversity and suggested additional mechanisms for taxonomic and functional characterization of the urban microbiome. Considering the great impact of urban microbiomes on human life, our study can also facilitate the microbial interaction analysis between human and urban environment.

The bone-degrading enzyme machinery: From multi-component understanding to the treatment of residues from the meat industry.

Many microorganisms feed on the tissue and recalcitrant bone materials from dead animals, however little is known about the collaborative effort and characteristics of their enzymes. In this study, microbial metagenomes from symbionts of the marine bone-dwelling worm Osedax mucofloris, and from microbial biofilms growing on experimentally deployed bone surfaces were screened for specialized bone-degrading enzymes. A total of 2,043 taxonomically (closest match within 40 phyla) and functionally (1 proteolytic and 9 glycohydrolytic activities) diverse and non-redundant sequences (median pairwise identity of 23.6%) encoding such enzymes were retrieved. The taxonomic assignation and the median identity of 72.2% to homologous proteins reflect microbial and functional novelty associated to a specialized bone-degrading marine community. Binning suggests that only one generalist hosting all ten targeted activities, working in synergy with multiple specialists hosting a few or individual activities. Collagenases were the most abundant enzyme class, representing 48% of the total hits. A total of 47 diverse enzymes, representing 8 hydrolytic activities, were produced in Escherichia coli, whereof 13 were soluble and active. The biochemical analyses revealed a wide range of optimal pH (4.0-7.0), optimal temperature (5-65 °C), and of accepted substrates, specific to each microbial enzyme. This versatility may contribute to a high environmental plasticity of bone-degrading marine consortia that can be confronted to diverse habitats and bone materials. Through bone-meal degradation tests, we further demonstrated that some of these enzymes, particularly those from Flavobacteriaceae and Marinifilaceae, may be an asset for development of new value chains in the biorefinery industry.

Diel Protein Regulation of Marine Picoplanktonic Communities Assessed by Metaproteomics.

The diel cycle is of enormous biological importance in that it imposes temporal structure on ecosystem productivity. In the world's oceans, microorganisms form complex communities that carry out about half of photosynthesis and the bulk of life-sustaining nutrient cycling. How the functioning of microbial communities is impacted by day and night periods in surface seawater remains to be elucidated. In this study, we compared the day and night metaproteomes of the free-living and the particle-attached bacterial fractions from picoplanktonic communities sampled from the northwest Mediterranean Sea surface. Our results showed similar taxonomic distribution of free-living and particle-attached bacterial populations, with Alphaproteobacteria, Gammaproteobacteria and Cyanobacteria being the most active members. Comparison of the day and night metaproteomes revealed that free-living and particle-attached bacteria were more active during the day and the night, respectively. Interestingly, protein diel variations were observed in the photoautotroph Synechococcales and in (photo)-heterotrophic bacteria such as Flavobacteriales, Pelagibacterales and Rhodobacterales. Moreover, our data demonstrated that diel cycle impacts light-dependent processes such as photosynthesis and UV-stress response in Synechococcales and Rhodobacterales, respectively, while the protein regulation from the ubiquitous Pelagibacterales remained stable over time. This study unravels, for the first time, the diel variation in the protein expression of major free-living and particle-attached microbial players at the sea surface, totaling an analysis of eight metaproteomes.

Machine Learning Predicts the Presence of 2,4,6-Trinitrotoluene in Sediments of a Baltic Sea Munitions Dumpsite Using Microbial Community Compositions.

Bacteria are ubiquitous and live in complex microbial communities. Due to differences in physiological properties and niche preferences among community members, microbial communities respond in specific ways to environmental drivers, potentially resulting in distinct microbial fingerprints for a given environmental state. As proof of the principle, our goal was to assess the opportunities and limitations of machine learning to detect microbial fingerprints indicating the presence of the munition compound 2,4,6-trinitrotoluene (TNT) in southwestern Baltic Sea sediments. Over 40 environmental variables including grain size distribution, elemental composition, and concentration of munition compounds (mostly at pmol⋅g-1 levels) from 150 sediments collected at the near-to-shore munition dumpsite Kolberger Heide by the German city of Kiel were combined with 16S rRNA gene amplicon sequencing libraries. Prediction was achieved using Random Forests (RFs); the robustness of predictions was validated using Artificial Neural Networks (ANN). To facilitate machine learning with microbiome data we developed the R package phyloseq2ML. Using the most classification-relevant 25 bacterial genera exclusively, potentially representing a TNT-indicative fingerprint, TNT was predicted correctly with up to 81.5% balanced accuracy. False positive classifications indicated that this approach also has the potential to identify samples where the original TNT contamination was no longer detectable. The fact that TNT presence was not among the main drivers of the microbial community composition demonstrates the sensitivity of the approach. Moreover, environmental variables resulted in poorer prediction rates than using microbial fingerprints. Our results suggest that microbial communities can predict even minor influencing factors in complex environments, demonstrating the potential of this approach for the discovery of contamination events over an integrated period of time. Proven for a distinct environment future studies should assess the ability of this approach for environmental monitoring in general.

Genomic and proteomic profiles of biofilms on microplastics are decoupled from artificial surface properties.

Microplastics in marine ecosystems are colonized by diverse prokaryotic and eukaryotic communities. How these communities and their functional profiles are shaped by the artificial surfaces remains broadly unknown. In order to close this knowledge gap, we set up an in situ experiment with pellets of the polyolefin polymer polyethylene (PE), the aromatic hydrocarbon polymer polystyrene (PS), and wooden beads along a coastal to estuarine gradient in the Baltic Sea, Germany. We used an integrated metagenomics/metaproteomics approach to evaluate the genomic potential as well as protein expression levels of aquatic plastic biofilms. Our results suggest that material properties had a minor influence on the plastic-associated assemblages, as genomic and proteomic profiles of communities associated with the structurally different polymers PE and PS were highly similar, hence polymer-unspecific. Instead, it seemed that these communities were shaped by biogeographic factors. Wood, on the other hand, induced the formation of substrate-specific biofilms and served as nutrient source itself. Our study indicates that, while PE and PS microplastics may be relevant in the photic zone as opportunistic colonization grounds for phototrophic microorganisms, they appear not to be subject to biodegradation or serve as vectors for pathogenic microorganisms in marine habitats.

Candidatus Sulfurimonas marisnigri sp. nov. and Candidatus Sulfurimonas baltica sp. nov., thiotrophic manganese oxide reducing chemolithoautotrophs of the class Campylobacteria isolated from the pelagic redoxclines of the Black Sea and the Baltic Sea.

Species of the genus Sulfurimonas are reported and isolated from terrestrial habitats and marine sediments and water columns with steep redox gradients. Here we report on the isolation of strains SoZ1 and GD2 from the pelagic redoxcline of the Black Sea and the Baltic Sea, respectively. Both strains are gram-stain-negative and appear as short and slightly curved motile rods. The autecological preferences for growth of strain SoZ1 were 0-25°C (optimum 20°C), pH 6.5-9.0 (optimum pH 7.5-8.0) and salinity 10-40gL-1 (optimum 25gL-1). Preferences for growth of strain GD2 were 0-20°C (optimum 15°C), pH 7.0-8.0 (optimum pH 7.0-7.5) and salinity 5-40gL-1 (optimum 21gL-1). Strain SoZ1 grew chemolithoautotrophically, while strain GD2 also showed heterotrophic growth with short chained fatty acids as carbon source. Both species utilized hydrogen (H2), sulfide (H2S here taken as the sum of H2S, HS- and S2-), elemental sulfur (S0) and thiosulfate (S2O32-) as electron donors and nitrate (NO3-), oxygen (O2) and particulate manganese oxide (MnO2) as electron acceptors. Based on 16S rRNA gene sequence similarity, both strains cluster within the genus Sulfurimonas with Sulfurimonas gotlandica GD1T as the closest cultured relative species with a sequence similarity of 96.74% and 96.41% for strain SoZ1 and strain GD2, respectively. Strains SoZ1 and GD2 share a ribosomal 16S sequence similarity of 99.27% and were demarcated based on average nucleotide identity and average amino acid identity of the whole genome sequence. These calculations have been applied to the whole genus. We propose the names Candidatus Sulfurimonas marisnigri sp. nov. and Candidatus Sulfurimonas baltica sp. nov. for the thiotrophic manganese reducing culture isolates from the Black Sea and Baltic Sea, respectively.

Synergistic biodegradation of aromatic-aliphatic copolyester plastic by a marine microbial consortium.

The degradation of synthetic polymers by marine microorganisms is not as well understood as the degradation of plastics in soil and compost. Here, we use metagenomics, metatranscriptomics and metaproteomics to study the biodegradation of an aromatic-aliphatic copolyester blend by a marine microbial enrichment culture. The culture can use the plastic film as the sole carbon source, reaching maximum conversion to CO2 and biomass in around 15 days. The consortium degrades the polymer synergistically, with different degradation steps being performed by different community members. We identify six putative PETase-like enzymes and four putative MHETase-like enzymes, with the potential to degrade aliphatic-aromatic polymers and their degradation products, respectively. Our results show that, although there are multiple genes and organisms with the potential to perform each degradation step, only a few are active during biodegradation.