The fatty liver disease-causing protein PNPLA3-I148M alters lipid droplet-Golgi dynamics.

Nonalcoholic fatty liver disease, recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), is a progressive metabolic disorder that begins with aberrant triglyceride accumulation in the liver and can lead to cirrhosis and cancer. A common variant in the gene , encoding the protein PNPLA3-I148M, is the strongest known genetic risk factor for MASLD. Despite its discovery 20 y ago, the function of PNPLA3, and now the role of PNPLA3-I148M, remain unclear.

Revealing the dynamics and mechanisms of bacterial interactions in cheese production with metabolic modelling.

Cheese taste and flavour properties result from complex metabolic processes occurring in microbial communities. A deeper understanding of such mechanisms makes it possible to improve both industrial production processes and end-product quality through the design of microbial consortia. In this work, we caracterise the metabolism of a three-species community consisting of Lactococcus lactis, Lactobacillus plantarum and Propionibacterium freudenreichii during a seven-week cheese production process.

Community-scale models of microbiomes: Articulating metabolic modelling and metagenome sequencing.

Building models is essential for understanding the functions and dynamics of microbial communities. Metabolic models built on genome-scale metabolic network reconstructions (GENREs) are especially relevant as a means to decipher the complex interactions occurring among species. Model reconstruction increasingly relies on metagenomics, which permits direct characterisation of naturally occurring communities that may contain organisms that cannot be isolated or cultured.

The fatty liver disease-causing protein PNPLA3-I148M alters lipid droplet-Golgi dynamics.

Non-alcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), is a progressive metabolic disorder that begins with aberrant triglyceride accumulation in the liver and can lead to cirrhosis and cancer. A common variant in the gene , encoding the protein PNPLA3-I148M, is the strongest known genetic risk factor for MASLD to date. Despite its discovery twenty years ago, the function of PNPLA3, and now the role of PNPLA3-I148M, remain unclear.

Quantitative measurement of the requirement of diverse protein degradation pathways in MHC class I peptide presentation.

Peptides from degradation of intracellular proteins are continuously displayed by major histocompatibility complex (MHC) class I. To better understand origins of these peptides, we performed a comprehensive census of the class I peptide repertoire in the presence and absence of ubiquitin-proteasome system (UPS) activity upon developing optimized methodology to enrich for and quantify these peptides. Whereas most class I peptides are dependent on the UPS for their generation, a surprising 30%, enriched in peptides of mitochondrial origin, appears independent of the UPS.

Proteasome Inhibitors: Harnessing Proteostasis to Combat Disease.

The proteasome is the central component of the main cellular protein degradation pathway. During the past four decades, the critical function of the proteasome in numerous physiological processes has been revealed, and proteasome activity has been linked to various human diseases. The proteasome prevents the accumulation of misfolded proteins, controls the cell cycle, and regulates the immune response, to name a few important roles for this macromolecular "machine.

Lipopolysaccharide is transported to the cell surface by a membrane-to-membrane protein bridge.

Gram-negative bacteria have an outer membrane that serves as a barrier to noxious agents in the environment. This protective function is dependent on lipopolysaccharide, a large glycolipid located in the outer leaflet of the outer membrane. Lipopolysaccharide is synthesized at the cytoplasmic membrane and must be transported to the cell surface.

The Antibiotic Novobiocin Binds and Activates the ATPase That Powers Lipopolysaccharide Transport.

Novobiocin is an orally active antibiotic that inhibits DNA gyrase by binding the ATP-binding site in the ATPase subunit. Although effective against Gram-positive pathogens, novobiocin has limited activity against Gram-negative organisms due to the presence of the lipopolysaccharide-containing outer membrane, which acts as a permeability barrier. Using a novobiocin-sensitive Escherichia coli strain with a leaky outer membrane, we identified a mutant with increased resistance to novobiocin.

Many interspecific chromosomal introgressions are highly prevalent in Holarctic Saccharomyces uvarum strains found in human-related fermentations.

In the last two decades, the extensive genome sequencing of strains belonging to the Saccharomyces genus has revealed the complex reticulated evolution of this group. Among the various evolutionary mechanisms described, the introgression of large chromosomal regions resulting from interspecific hybridization has recently shed light on Saccharomyces uvarum species. In this work we provide the de novo assembled genomes of four S.

Lipopolysaccharide transport and assembly at the outer membrane: the PEZ model.

Gram-negative bacteria have a double-membrane cellular envelope that enables them to colonize harsh environments and prevents the entry of many clinically available antibiotics. A main component of most outer membranes is lipopolysaccharide (LPS), a glycolipid containing several fatty acyl chains and up to hundreds of sugars that is synthesized in the cytoplasm. In the past two decades, the proteins that are responsible for transporting LPS across the cellular envelope and assembling it at the cell surface in Escherichia coli have been identified, but it remains unclear how they function.

Lipopolysaccharide transport to the cell surface: biosynthesis and extraction from the inner membrane.

The cell surface of most Gram-negative bacteria is covered with lipopolysaccharide (LPS). The network of charges and sugars provided by the dense packing of LPS molecules in the outer leaflet of the outer membrane interferes with the entry of hydrophobic compounds into the cell, including many antibiotics. In addition, LPS can be recognized by the immune system and plays a crucial role in many interactions between bacteria and their animal hosts.

Lipopolysaccharide transport to the cell surface: periplasmic transport and assembly into the outer membrane.

Gram-negative bacteria possess an outer membrane (OM) containing lipopolysaccharide (LPS). Proper assembly of the OM not only prevents certain antibiotics from entering the cell, but also allows others to be pumped out. To assemble this barrier, the seven-protein lipopolysaccharide transport (Lpt) system extracts LPS from the outer leaflet of the inner membrane (IM), transports it across the periplasm and inserts it selectively into the outer leaflet of the OM.

Phylogenomic Analysis of Oenococcus oeni Reveals Specific Domestication of Strains to Cider and Wines.

Oenococcus oeni is a lactic acid bacteria species encountered particularly in wine, where it achieves the malolactic fermentation. Molecular typing methods have previously revealed that the species is made of several genetic groups of strains, some being specific to certain types of wines, ciders or regions. Here, we describe 36 recently released O.

Mimoza: web-based semantic zooming and navigation in metabolic networks.

Background: The complexity of genome-scale metabolic models makes them quite difficult for human users to read, since they contain thousands of reactions that must be included for accurate computer simulation. Interestingly, hidden similarities between groups of reactions can be discovered, and generalized to reveal higher-level patterns.

Results: The web-based navigation system Mimoza allows a human expert to explore metabolic network models in a semantically zoomable manner: The most general view represents the compartments of the model; the next view shows the generalized versions of reactions and metabolites in each compartment; and the most detailed view represents the initial network with the generalization-based layout (where similar metabolites and reactions are placed next to each other).

Pantograph: A template-based method for genome-scale metabolic model reconstruction.

Genome-scale metabolic models are a powerful tool to study the inner workings of biological systems and to guide applications. The advent of cheap sequencing has brought the opportunity to create metabolic maps of biotechnologically interesting organisms. While this drives the development of new methods and automatic tools, network reconstruction remains a time-consuming process where extensive manual curation is required.

Diversity and variability of NOD-like receptors in fungi.

Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are intracellular receptors that control innate immunity and other biotic interactions in animals and plants. NLRs have been characterized in plant and animal lineages, but in fungi, this gene family has not been systematically described. There is however previous indications of the involvement of NLR-like genes in nonself recognition and programmed cell death in fungi.

Draft Genome Sequence of Rhodosporidium toruloides CECT1137, an Oleaginous Yeast of Biotechnological Interest.

We report the sequencing of the basidiomycetous yeast Rhodosporidium toruloides CECT1137. The current assembly comprises 62 scaffolds, for a total size of ca. 20.

Modeling acclimatization by hybrid systems: condition changes alter biological system behavior models.

In order to describe the dynamic behavior of a complex biological system, it is useful to combine models integrating processes at different levels and with temporal dependencies. Such combinations are necessary for modeling acclimatization, a phenomenon where changes in environmental conditions can induce drastic changes in the behavior of a biological system. In this article we formalize the use of hybrid systems as a tool to model this kind of biological behavior.

A Gondwanan imprint on global diversity and domestication of wine and cider yeast Saccharomyces uvarum.

In addition to Saccharomyces cerevisiae, the cryotolerant yeast species S. uvarum is also used for wine and cider fermentation but nothing is known about its natural history. Here we use a population genomics approach to investigate its global phylogeography and domestication fingerprints using a collection of isolates obtained from fermented beverages and from natural environments on five continents.

The complete genome of Blastobotrys (Arxula) adeninivorans LS3 - a yeast of biotechnological interest.

Background: The industrially important yeast Blastobotrys (Arxula) adeninivorans is an asexual hemiascomycete phylogenetically very distant from Saccharomyces cerevisiae. Its unusual metabolic flexibility allows it to use a wide range of carbon and nitrogen sources, while being thermotolerant, xerotolerant and osmotolerant.

Results: The sequencing of strain LS3 revealed that the nuclear genome of A.

Knowledge-based generalization of metabolic models.

Genome-scale metabolic model reconstruction is a complicated process beginning with (semi-)automatic inference of the reactions participating in the organism's metabolism, followed by many iterations of network analysis and improvement. Despite advances in automatic model inference and analysis tools, reconstruction may still miss some reactions or add erroneous ones. Consequently, a human expert's analysis of the model will continue to play an important role in all the iterations of the reconstruction process.

Knowledge-based generalization of metabolic networks: a practical study.

The complex process of genome-scale metabolic network reconstruction involves semi-automatic reaction inference, analysis, and refinement through curation by human experts. Unfortunately, decisions by experts are hampered by the complexity of the network, which can mask errors in the inferred network. In order to aid an expert in making sense out of the thousands of reactions in the organism's metabolism, we developed a method for knowledge-based generalization that provides a higher-level view of the network, highlighting the particularities and essential structure, while hiding the details.

Decoupling catalytic activity from biological function of the ATPase that powers lipopolysaccharide transport.

The cell surface of Gram-negative bacteria contains lipopolysaccharides (LPS), which provide a barrier against the entry of many antibiotics. LPS assembly involves a multiprotein LPS transport (Lpt) complex that spans from the cytoplasm to the outer membrane. In this complex, an unusual ATP-binding cassette transporter is thought to power the extraction of LPS from the outer leaflet of the cytoplasmic membrane and its transport across the cell envelope.

QTL dissection of Lag phase in wine fermentation reveals a new translocation responsible for Saccharomyces cerevisiae adaptation to sulfite.

Quantitative genetics and QTL mapping are efficient strategies for deciphering the genetic polymorphisms that explain the phenotypic differences of individuals within the same species. Since a decade, this approach has been applied to eukaryotic microbes such as Saccharomyces cerevisiae in order to find natural genetic variations conferring adaptation of individuals to their environment. In this work, a QTL responsible for lag phase duration in the alcoholic fermentation of grape juice was dissected by reciprocal hemizygosity analysis.