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"Simon, K"
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The microbiome extends host evolutionary potential
The microbiome shapes many host traits, yet the biology of microbiomes challenges traditional evolutionary models. Here, we illustrate how integrating the microbiome into quantitative genetics can help untangle complexities of host-microbiome evolution. We describe two general ways in which the microbiome may affect host evolutionary potential: by shifting the mean host phenotype and by changing the variance in host phenotype in the population. We synthesize the literature across diverse taxa and discuss how these scenarios could shape the host response to selection. We conclude by outlining key avenues of research to improve our understanding of the complex interplay between hosts and microbiomes.
The microbiome is becoming recognized as a key determinant of host phenotype. Here, Henry et al. present a framework for building our understanding of how the microbiome also influences host evolution, review empirical examples and research approaches, and highlight emerging questions.
Journal Article
Actin cytoskeleton and complex cell architecture in an Asgard archaeon
Asgard archaea are considered to be the closest known relatives of eukaryotes. Their genomes contain hundreds of eukaryotic signature proteins (ESPs), which inspired hypotheses on the evolution of the eukaryotic cell
1
–
3
. A role of ESPs in the formation of an elaborate cytoskeleton and complex cellular structures has been postulated
4
–
6
, but never visualized. Here we describe a highly enriched culture of ‘
Candidatus
Lokiarchaeum ossiferum’, a member of the Asgard phylum, which thrives anaerobically at 20 °C on organic carbon sources. It divides every 7–14 days, reaches cell densities of up to 5 × 10
7
cells per ml and has a significantly larger genome compared with the single previously cultivated Asgard strain
7
. ESPs represent 5% of its protein-coding genes, including four actin homologues. We imaged the enrichment culture using cryo-electron tomography, identifying ‘
Ca
. L. ossiferum’ cells on the basis of characteristic expansion segments of their ribosomes. Cells exhibited coccoid cell bodies and a network of branched protrusions with frequent constrictions. The cell envelope consists of a single membrane and complex surface structures. A long-range cytoskeleton extends throughout the cell bodies, protrusions and constrictions. The twisted double-stranded architecture of the filaments is consistent with F-actin. Immunostaining indicates that the filaments comprise Lokiactin—one of the most highly conserved ESPs in Asgard archaea. We propose that a complex actin-based cytoskeleton predated the emergence of the first eukaryotes and was a crucial feature in the evolution of the Asgard phylum by scaffolding elaborate cellular structures.
Culture and analysis of ‘
Candidatus
Lokiarchaeum ossiferum’—a member of the Asgard phylum—reveals an elaborate cell architecture with extensive membranous protrusions.
Journal Article
SepF is the FtsZ anchor in archaea, with features of an ancestral cell division system
Most archaea divide by binary fission using an FtsZ-based system similar to that of bacteria, but they lack many of the divisome components described in model bacterial organisms. Notably, among the multiple factors that tether FtsZ to the membrane during bacterial cell constriction, archaea only possess SepF-like homologs. Here, we combine structural, cellular, and evolutionary analyses to demonstrate that SepF is the FtsZ anchor in the human-associated archaeon
Methanobrevibacter smithii
. 3D super-resolution microscopy and quantitative analysis of immunolabeled cells show that SepF transiently co-localizes with FtsZ at the septum and possibly primes the future division plane.
M. smithii
SepF binds to membranes and to FtsZ, inducing filament bundling. High-resolution crystal structures of archaeal SepF alone and in complex with the FtsZ C-terminal domain (FtsZ
CTD
) reveal that SepF forms a dimer with a homodimerization interface driving a binding mode that is different from that previously reported in bacteria. Phylogenetic analyses of SepF and FtsZ from bacteria and archaea indicate that the two proteins may date back to the Last Universal Common Ancestor (LUCA), and we speculate that the archaeal mode of SepF/FtsZ interaction might reflect an ancestral feature. Our results provide insights into the mechanisms of archaeal cell division and pave the way for a better understanding of the processes underlying the divide between the two prokaryotic domains.
Most archaea divide by binary fission using an FtsZ-based system that is poorly understood. Here, the authors combine structural, cellular, and evolutionary analyses to show that the SepF protein acts as the FtsZ anchor in the archaeon
Methanobrevibacter smithii
.
Journal Article
Epidemiological investigation on hand hygiene knowledge and behaviour: a cross-sectional study on gender disparity
Background
The hand hygiene (HH) behaviour of the general public and its effect on illnesses are issues of growing importance. Gender is associated with HH behaviour. HH efficiency is a combination of washing efficiency and hand drying, but information about the knowledge level and HH behaviour of the general public is relatively limited. The findings of this cross-sectional study can substantially contribute to the understanding on the knowledge gap and public behaviour towards HH, thereby providing information on gender-specific health promotion activities and campaigns to improve HH compliance.
Methods
An epidemiological investigation by using a cross-sectional study design on the general public was conducted either via an online platform (SurveyMonkey) or paper-and-pen methods. The hand-washing and -drying questionnaire was used for data collection.
Results
A total of 815 valid questionnaires were collected. Majority of the respondents can differentiate the diseases that can or cannot be transmitted with poor HH, but the HH knowledge of the respondents was relatively inadequate. The female respondents had a significantly better HH knowledge than male respondents. The multiple regression analysis results also indicated that females had a significantly higher knowledge score by 0.288 towards HH than males after adjusting for age and education level. Although the majority of the respondents indicated that they performed hand cleaning under different specific situations, they admitted only using water instead of washing their hands with soap. More males than females dried their hands on their own clothing, whereas more females dried their hands through air evaporation. The average time of using warm hand dryers was generally inadequate amongst the respondents.
Conclusions
Being a female, middle-aged and having tertiary education level are protective factors to improve HH knowledge. Misconceptions related to the concepts associated with HH were noted amongst the public. Self-reported practice on hand drying methods indicated that additional education was needed. The findings of this study can provide information on gender-specific health promotion activities and creative campaigns to achieve sustained improvement in HH practices.
Journal Article
Evaluation of circulating plasma proteins in breast cancer using Mendelian randomisation
Biomarkers for early detection of breast cancer may complement population screening approaches to enable earlier and more precise treatment. The blood proteome is an important source for biomarker discovery but so far, few proteins have been identified with breast cancer risk. Here, we measure 2929 unique proteins in plasma from 598 women selected from the Karolinska Mammography Project to explore the association between protein levels, clinical characteristics, and gene variants, and to identify proteins with a causal role in breast cancer. We present 812 cis-acting protein quantitative trait loci for 737 proteins which are used as instruments in Mendelian randomisation analyses of breast cancer risk. Of those, we present five proteins (CD160, DNPH1, LAYN, LRRC37A2 and TLR1) that show a potential causal role in breast cancer risk with confirmatory results in independent cohorts. Our study suggests that these proteins should be further explored as biomarkers and potential drug targets in breast cancer.
Proteomics of blood samples is a promising avenue for cancer diagnosis. Here, the authors conduct Mendelian randomisation analysis of protein levels across multiple cohorts, and identify 5 proteins that show promise as biomarkers for the long-term risk of breast cancer, and as potential drug targets.
Journal Article
A high-pressure bioreactor system for the cultivation of Methanothermobacter marburgensis on advanced growth media for sustainable energy applications
The global transition towards sustainable energy necessitates rapid innovations in renewable technology, with biomethanation emerging as a promising approach. Methanogenic archaea, notably
Methanothermobacter marburgensis
, play a pivotal role in the biogenesis of biomethane as a renewable energy vector. This research introduces a new second-generation Simultaneous Bioreactor System (SBRS-II), a high-pressure cultivation platform engineered to optimize microbial gas fermentation. A novel sulfate-based growth medium (MM-CF-S) was formulated to substitute conventional chloride salts, thereby minimizing corrosion risks in steel reactors and eliminating the toxic compound NiCl
2
·6 H
2
O, which enhances safety during large-scale deployment. Comparative analyses indicate that the new medium markedly boosts methane production rates, attaining a maximum of 285.86 ± 22.94 mmol L
−1
h
−1
, approximately doubling the baseline. Additionally, metrics of biomass accumulation and specific methane productivity observed improvements, with
reaching 216.85 ± 17.54 mmol g
−1
h
−1
. The sulfate medium also preserved pH stability under high-pressure conditions, ensuring physiological viability essential for
M. marburgensis
proliferation. Integration of the SBRS-II platform with the MM-CF-S medium signifies a significant advancement toward scalable, efficient biomethanation technologies, highlighting the potential of methanogenic archaea in renewable energy applications and establishing a foundation for further process optimization to meet industrial-scale demands.
Journal Article
Protein stability prediction by fine-tuning a protein language model on a mega-scale dataset
Protein stability plays a crucial role in a variety of applications, such as food processing, therapeutics, and the identification of pathogenic mutations. Engineering campaigns commonly seek to improve protein stability, and there is a strong interest in streamlining these processes to enable rapid optimization of highly stabilized proteins with fewer iterations. In this work, we explore utilizing a mega-scale dataset to develop a protein language model optimized for stability prediction. ESM therm is trained on the folding stability of 528k natural and de novo sequences derived from 461 protein domains and can accommodate deletions, insertions, and multiple-point mutations. We show that a protein language model can be fine-tuned to predict folding stability. ESM therm performs reasonably on small protein domains and generalizes to sequences distal from the training set. Lastly, we discuss our model’s limitations compared to other state-of-the-art methods in generalizing to larger protein scaffolds. Our results highlight the need for large-scale stability measurements on a diverse dataset that mirrors the distribution of sequence lengths commonly observed in nature.
Journal Article
Quantitative analysis of amino acid excretion and consumption by Methanothermobacter marburgensis in fed-batch cultivation mode
The methanogenic archaeon
Methanothermobacter marburgensis
offers a promising alternative to traditional bacterial systems for the sustainable production of proteinogenic amino acids (AAs), eliminating the need for sugar-based feedstock. In this study, we quantitatively examined AA excretion and consumption in fed-batch cultivation mode in bioreactors under varying ammonium (NH
4
+
) concentrations and gas compositions.
M. marburgensis
demonstrated excretion of a wide spectrum of AAs with distinct profiles shaped by nitrogen availability. While high NH
4
+
concentrations suppressed total AA excretion, NH
4
+
limited conditions triggered alanine accumulation followed by its re-assimilation, suggesting a regulatory mechanism linked to nitrogen stress. Moreover, carbon limitation and nitrogen excess resulted in the production of an AA pattern including asparagine. Despite lower overall productivity compared to engineered bacterial strains,
M. marburgensis
exhibited the unique ability to simultaneously excrete multiple AAs without requiring organic carbon input. These findings advance the feasibility of using methanogens for AA bioprocessing and the development of archaea as next-generation microbial cell factories.
Journal Article