A computational model of Pseudomonas syringae metabolism unveils a role for branched-chain amino acids in Arabidopsis leaf colonization.

Bacterial pathogens adapt their metabolism to the plant environment to successfully colonize their hosts. In our efforts to uncover the metabolic pathways that contribute to the colonization of Arabidopsis thaliana leaves by Pseudomonas syringae pv tomato DC3000 (Pst DC3000), we created iPst19, an ensemble of 100 genome-scale network reconstructions of Pst DC3000 metabolism. We developed a novel approach for gene essentiality screens, leveraging the predictive power of iPst19 to identify core and ancillary condition-specific essential genes.

Histone Deacetylase Inhibition by Gut Microbe-Generated Short-Chain Fatty Acids Entrains Intestinal Epithelial Circadian Rhythms.

Background & Aims: The circadian clock orchestrates ∼24-hour oscillations of gastrointestinal epithelial structure and function that drive diurnal rhythms in gut microbiota. Here, we use experimental and computational approaches in intestinal organoids to reveal reciprocal effects of gut microbial metabolites on epithelial timekeeping by an epigenetic mechanism.

Methods: We cultured enteroids in media supplemented with sterile supernatants from the altered Schaedler Flora (ASF), a defined murine microbiota.

Comparative analyses of parasites with a comprehensive database of genome-scale metabolic models.

Protozoan parasites cause diverse diseases with large global impacts. Research on the pathogenesis and biology of these organisms is limited by economic and experimental constraints. Accordingly, studies of one parasite are frequently extrapolated to infer knowledge about another parasite, across and within genera.

Enhancing Microbiome Research through Genome-Scale Metabolic Modeling.

Construction and analysis of genome-scale metabolic models (GEMs) is a well-established systems biology approach that can be used to predict metabolic and growth phenotypes. The ability of GEMs to produce mechanistic insight into microbial ecological processes makes them appealing tools that can open a range of exciting opportunities in microbiome research. Here, we briefly outline these opportunities, present current rate-limiting challenges for the trustworthy application of GEMs to microbiome research, and suggest approaches for moving the field forward.

Megasphaera in the Stool Microbiota Is Negatively Associated With Diarrheal Cryptosporidiosis.

Background: The protozoan parasites in the Cryptosporidium genus cause both acute diarrheal disease and subclinical (ie, nondiarrheal) disease. It is unclear if the microbiota can influence the manifestation of diarrhea during a Cryptosporidium infection.

Methods: To characterize the role of the gut microbiota in diarrheal cryptosporidiosis, the microbiome composition of both diarrheal and surveillance Cryptosporidium-positive fecal samples from 72 infants was evaluated using 16S ribosomal RNA gene sequencing.

Mucosal Genomics Implicate Lymphocyte Activation and Lipid Metabolism in Refractory Environmental Enteric Dysfunction.

Background & Aims: Environmental enteric dysfunction (EED) limits the Sustainable Development Goals of improved childhood growth and survival. We applied mucosal genomics to advance our understanding of EED.

Methods: The Study of Environmental Enteropathy and Malnutrition (SEEM) followed 416 children from birth to 24 months in a rural district in Pakistan.

Medusa: Software to build and analyze ensembles of genome-scale metabolic network reconstructions.

Uncertainty in the structure and parameters of networks is ubiquitous across computational biology. In constraint-based reconstruction and analysis of metabolic networks, this uncertainty is present both during the reconstruction of networks and in simulations performed with them. Here, we present Medusa, a Python package for the generation and analysis of ensembles of genome-scale metabolic network reconstructions.

Publisher Correction: MEMOTE for standardized genome-scale metabolic model testing.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Guiding the Refinement of Biochemical Knowledgebases with Ensembles of Metabolic Networks and Machine Learning.

Mechanistic models explicitly represent hypothesized biological knowledge. As such, they offer more generalizability than data-driven models. However, identifying model curation efforts that improve performance for mechanistic models is nontrivial.

Uniting the un-united: should established non-unions of femoral shaft fractures initially treated with IM nails be treated by plate augmentation instead of exchange IM nailing? A systematic review.

The majority of femoral fractures are surgically treated with intramedullary nails. Non-union rate is low but challenging and costly if it occurs. There have been encouraging results from the use of augmentative plating as a treatment for non-union of femoral fractures.

Inferring Metabolic Mechanisms of Interaction within a Defined Gut Microbiota.

The diversity and number of species present within microbial communities create the potential for a multitude of interspecies metabolic interactions. Here, we develop, apply, and experimentally test a framework for inferring metabolic mechanisms associated with interspecies interactions. We perform pairwise growth and metabolome profiling of co-cultures of strains from a model mouse microbiota.

Combined Volar and Dorsal Approach for Fixation of Comminuted Intra-Articular Distal Radial Fractures.

 Multifragmentary intra-articular fractures displaced in multiple planes are a challenge. We use a reproducible technique of fracture and articular reduction using an initial volar approach targeting reduction in the volar lunate facet first with plate and unicortical locking screws. This creates a template for reduction in dorsal fragments through a dorsal approach.

A novel mouse model of Campylobacter jejuni enteropathy and diarrhea.

Campylobacter infections are among the leading bacterial causes of diarrhea and of 'environmental enteropathy' (EE) and growth failure worldwide. However, the lack of an inexpensive small animal model of enteric disease with Campylobacter has been a major limitation for understanding its pathogenesis, interventions or vaccine development. We describe a robust standard mouse model that can exhibit reproducible bloody diarrhea or growth failure, depending on the zinc or protein deficient diet and on antibiotic alteration of normal microbiota prior to infection.

Influential Parameters for the Analysis of Intracellular Parasite Metabolomics.

Metabolomics is increasingly popular for the study of pathogens. For the malaria parasite , both targeted and untargeted metabolomics have improved our understanding of pathogenesis, host-parasite interactions, and antimalarial drug treatment and resistance. However, purification and analysis procedures for performing metabolomics on intracellular pathogens have not been explored.

Novel co-culture plate enables growth dynamic-based assessment of contact-independent microbial interactions.

Interactions between microbes are central to the dynamics of microbial communities. Understanding these interactions is essential for the characterization of communities, yet challenging to accomplish in practice. There are limited available tools for characterizing diffusion-mediated, contact-independent microbial interactions.

Cross-modulation of pathogen-specific pathways enhances malnutrition during enteric co-infection with Giardia lamblia and enteroaggregative Escherichia coli.

Diverse enteropathogen exposures associate with childhood malnutrition. To elucidate mechanistic pathways whereby enteric microbes interact during malnutrition, we used protein deficiency in mice to develop a new model of co-enteropathogen enteropathy. Focusing on common enteropathogens in malnourished children, Giardia lamblia and enteroaggregative Escherichia coli (EAEC), we provide new insights into intersecting pathogen-specific mechanisms that enhance malnutrition.

Increased Urinary Trimethylamine N-Oxide Following Cryptosporidium Infection and Protein Malnutrition Independent of Microbiome Effects.

Cryptosporidium infections have been associated with growth stunting, even in the absence of diarrhea. Having previously detailed the effects of protein deficiency on both microbiome and metabolome in this model, we now describe the specific gut microbial and biochemical effects of Cryptosporidium infection. Protein-deficient mice were infected with Cryptosporidium parvum oocysts for 6-13 days and compared with uninfected controls.

Percutaneous screw fixation of unstable ankle fractures in patients with poor soft tissues and significant co-morbidities.

Introduction: We describe a minimally invasive technique to stabilise unstable ankle fractures by inserting a 100mm screw up the fibula medullary canal along with percutaneous screw fixation of the medial malleolus if required. This technique is utilised in patients with poor soft tissues and significant co-morbidities where the fracture cannot be adequately controlled by a cast alone.

Patients And Methods: Retrospective review of 23 patients the average age being 70 years (29-89) and 74% had significant co-morbidities.

Magnetic resonance imaging investigation of radio-lunate relations: use in assessing distal radial fracture reduction.

Unlabelled: Reformatted magnetic resonance imaging scans of 27 normal wrists were examined in incremental degrees of rotation around the central axis of the radial shaft to 30° in both directions from true lateral. A line was superimposed on the outer border of the radial dorsal cortex and continued distally to the carpal region. Measurements were made from the superior pole of the lunate to this line.

Systems-level metabolism of the altered Schaedler flora, a complete gut microbiota.

The altered Schaedler flora (ASF) is a model microbial community with both in vivo and in vitro relevance. Here we provide the first characterization of the ASF community in vitro, independent of a murine host. We compared the functional genetic content of the ASF to wild murine metagenomes and found that the ASF functionally represents wild microbiomes better than random consortia of similar taxonomic composition.

Protein- and zinc-deficient diets modulate the murine microbiome and metabolic phenotype.

Background: Environmental enteropathy, which is linked to undernutrition and chronic infections, affects the physical and mental growth of children in developing areas worldwide. Key to understanding how these factors combine to shape developmental outcomes is to first understand the effects of nutritional deficiencies on the mammalian system including the effect on the gut microbiota.

Objective: We dissected the nutritional components of environmental enteropathy by analyzing the specific metabolic and gut-microbiota changes that occur in weaned-mouse models of zinc or protein deficiency compared with well-nourished controls.

Metabolic network modeling of microbial communities.

Genome-scale metabolic network reconstructions and constraint-based analyses are powerful methods that have the potential to make functional predictions about microbial communities. Genome-scale metabolic networks are used to characterize the metabolic functions of microbial communities via several techniques including species compartmentalization, separating species-level and community-level objectives, dynamic analysis, the 'enzyme-soup' approach, multiscale modeling, and others. There are many challenges in the field, including a need for tools that accurately assign high-level omics signals to individual community members, the need for improved automated network reconstruction methods, and novel algorithms for integrating omics data and engineering communities.