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Biology subjects

Schroeder, F.

Publications and source records attributed to Schroeder, F..

8 recordsLinked to original sources

Dietary fiber selectively regulates intestinal persistence of probiotic bifidobacteria

Bifidobacteria dominate the gut microbiota of breast-fed infants, and are strongly associated with human health, including immune regulation, colonization resistance, and protection against inflammation. However, bifidobacteria persist at high abundance after weaning in only a subset of individuals, and the factors that regulate intestinal persistence of bifidobacteria are poorly understood. Using gnotobiotic mouse models, we identified a common dietary fiber, raffinose, as a critical determinant of bifidobacterial persistence during microbial transitions associated with weaning. Bifidobacterial persistence depends on an intact raffinose utilization operon and is associated with disease resistance and restrained inflammation in adult mice. Specific dietary fiber recommendations commencing at weaning are a potential strategy to maintain bifidobacteria persistence beyond infancy, with potential long-term benefits for host resilience and reduced risk of inflammatory disease.

microbiology↗

DNA Staples: An oligonucleotide library for data storage and computing

DNA offers exceptional information density and stability, making it a promising medium for long-term data storage. However, the high cost of DNA synthesis and data retrieval remain key barriers to large-scale deployment. In this paper, we present DNA staples, a multipurpose library of short single-stranded DNA sequences that enables the encoding of arbitrary digital data by enzymatic assembly. Flexible encoding schemes allow the same presynthesized strand library to be used across applications, significantly reducing synthesis requirements while supporting diverse data representations. Using a restricted library also confers inherent error correction. In addition to storage, the library enables creation of computational DNA modules that perform highly parallel operations directly on stored data. This framework provides a cost-efficient approach to molecular data storage and supports integrated storage-computation at the DNA level.

synthetic biology↗

Evolutionarily related host and microbial pathways regulate fat desaturation

Fatty acid desaturation is central to metazoan lipid metabolism and provides building blocks of membrane lipids and precursors of diverse signaling molecules. Nutritional conditions and associated microbiota regulate desaturase expression1-4, but the underlying mechanisms have remained unclear. Here, we show that endogenous and microbiota-dependent small molecule signals promote lipid desaturation via the nuclear receptor NHR-49/PPAR in C. elegans. Untargeted metabolomics of a {beta}-oxidation mutant, acdh-11, in which expression of the stearoyl-CoA desaturase FAT-7/SCD1 is constitutively increased, revealed accumulation of a {beta}- cyclopropyl fatty acid, becyp#1, that potently activates fat-7 expression via NHR-49. Biosynthesis of becyp#1 is strictly dependent on expression of cyclopropane synthase by associated bacteria, e.g., E. coli. Screening for structurally related endogenous metabolites revealed a {beta}-methyl fatty acid, bemeth#1, whose activity mimics that of microbiota-dependent becyp#1, but is derived from a methyltransferase, fcmt-1, that is conserved across Nematoda and likely originates from bacterial cyclopropane synthase via ancient horizontal gene transfer. Activation of fat-7 expression by these structurally similar metabolites is controlled by distinct mechanisms, as microbiota-dependent becyp#1 is metabolized by a dedicated {beta}-oxidation pathway, while the endogenous bemeth#1 is metabolized via -oxidation. Collectively, we demonstrate that evolutionarily related biosynthetic pathways in metazoan host and associated microbiota converge on NHR-49/PPAR to regulate fat desaturation.

biochemistry↗

Neuronally Produced Betaine Acts via a Novel Ligand Gated Ion Channel to Control Behavioural States

Trimethyl glycine, or betaine, is an amino acid derivative found in diverse organisms, from bacteria to plants and animals. It can function as an osmolyte to protect cells against osmotic stress, and building evidence suggests betaine may also play important functional roles in the nervous system. However, despite growing interest in betaines roles in the nervous system, few molecular mechanisms have been elucidated. Here we identify the expression of betaine synthesis pathway genes in the nervous system of the nematode worm, C. elegans. We show that betaine, produced in a single pair of interneurons, the RIMs, can control complex behavioural states. Moreover, we also identify and characterise a new betaine-gated inhibitory ligand gated ion channel, LGC-41, which is required for betaine related behavioural changes. Intriguingly we observed expression of LGC-41 in punctate structures across several sensory and interneurons, including those synaptically connected to the RIMs. Our data presents a neuronal molecular mechanism for the action of betaine, via a specific receptor, in the control of complex behaviour within the nervous system of C. elegans. This may suggest a much broader role for betaine in the regulation of animal nervous systems than previously recognised.

neuroscience↗

Computational metabolomics illuminates the lineage-specific diversification of resin glycoside acylsugars in the morning glory (Convolvulaceae) family

Acylsugars are a class of plant defense compounds produced across many distantly related families. Members of the horticulturally important morning glory (Convolvulaceae) family produce a diverse sub-class of acylsugars called resin glycosides (RGs), which comprise oligosaccharide cores, hydroxyacyl chain(s), and decorating aliphatic and aromatic acyl chains. While many RG structures are characterized, the extent of structural diversity of this class in different genera and species is not known. In this study, we asked whether there has been lineage-specific diversification of RG structures in different Convolvulaceae species that may suggest diversification of the underlying biosynthetic pathways. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was performed from root and leaf extracts of 26 species sampled in a phylogeny-guided manner. LC-MS/MS revealed thousands of peaks with signature RG fragmentation patterns with one species producing over 300 signals, mirroring the diversity in Solanaceae-type acylsugars. A novel RG from Dichondra argentea was characterized using Nuclear Magnetic Resonance spectroscopy, supporting previous observations of RGs with open hydroxyacyl chains instead of closed macrolactone ring structures. Substantial lineage-specific differentiation in utilization of sugars, hydroxyacyl chains, and decorating acyl chains was discovered, especially among Ipomoea and Convolvulus - the two largest genera in Convolvulaceae. Adopting a computational, knowledge-based strategy, we further developed a high-recall workflow that successfully explained ~72% of the MS/MS fragments, predicted the structural components of 11/13 previously characterized RGs, and partially annotated ~45% of the RGs. Overall, this study improves our understanding of phytochemical diversity and lays a foundation for characterizing the evolutionary mechanisms underlying RG diversification.

plant biology↗

Neuronal KGB-1 JNK MAPK signaling regulates the dauer developmental decision in response to environmental stress in C. elegans

In response to stressful growth conditions of high population density, food scarcity and elevated temperature, young larvae of nematode Caenorhabditis elegans can enter a developmentally arrested stage called dauer that is characterized by dramatic anatomic and metabolic remodeling. Genetic analysis of dauer formation of C. elegans has served as an experimental paradigm for the identification and characterization of conserved neuroendocrine signaling pathways. Here, we report the identification and characterization of a conserved JNK-like mitogen-activated protein kinase (MAPK) pathway that is required for dauer formation in response to environmental stressors. We observed that loss-of-function mutations in the MLK-1-MEK-1-KGB-1 MAPK pathway suppress dauer entry. Loss-of-function mutation in the VHP-1 MAPK phosphatase, a known negative regulator of KGB-1 signaling, results in constitutive dauer formation which is dependent on the presence of dauer pheromone but independent of diminished food levels or elevated temperatures. Our data suggest that KGB-1 pathway acts in the sensory neurons, in parallel to established insulin and TGF-{beta} signaling pathways, to transduce the dauer-inducing environmental cues of diminished food levels and elevated temperature.

developmental biology↗

Intestinal peroxisomal fatty acid β-oxidation regulates neural serotonin signaling through a feedback mechanism

The ability to coordinate behavioral responses with metabolic status is fundamental to the maintenance of energy homeostasis. In numerous species including C. elegans and mammals, neural serotonin signaling regulates a range of food-related behaviors. However, the mechanisms that integrate metabolic information with serotonergic circuits are poorly characterized. Here, we identify metabolic, molecular, and cellular components of a circuit that links peripheral metabolic state to serotonin-regulated behaviors in C. elegans. We find that blocking the entry of fatty acyl-CoAs into peroxisomal {beta}-oxidation in the intestine results in blunting of the effects of neural serotonin signaling on feeding and egg-laying behaviors. Comparative genomics and metabolomics revealed that interfering with intestinal peroxisomal {beta}-oxidation results in a modest global transcriptional change but significant changes to the metabolome, including a large number of changes in ascaroside and phospholipid species, some of which affect feeding behavior. We also identify body cavity neurons and an ether-a-go-go related (EAG) potassium channel that functions in these neurons as key cellular components of the circuitry linking peripheral metabolic signals to regulation of neural serotonin signaling. These data raise the possibility that the effects of serotonin on satiety may have their origins in feedback, homeostatic metabolic responses from the periphery.

physiology↗

Metabolome-scale genome-wide association studies reveal chemical diversity and genetic control of maize specialized metabolites

One Sentence SummaryHPLC-MS metabolite profiling of maize seedlings, in combination with genome-wide association studies, identifies numerous quantitative trait loci that influence the accumulation of foliar metabolites.\n\nAbstractCultivated maize (Zea mays) retains much of the genetic and metabolic diversity of its wild ancestors. Non-targeted HPLC-MS metabolomics using a diverse panel of 264 maize inbred lines identified a bimodal distribution in the prevalence of foliar metabolites. Although 15% of the detected mass features were present in >90% of the inbred lines, the majority were found in <50% of the samples. Whereas leaf bases and tips were differentiated primarily by flavonoid abundance, maize varieties (stiff-stalk, non-stiff-stalk, tropical, sweet corn, and popcorn) were differentiated predominantly by benzoxazinoid metabolites. Genome-wide association studies (GWAS), performed for 3,991 mass features from the leaf tips and leaf bases, showed that 90% have multiple significantly associated loci scattered across the genome. Several quantitative trait locus hotspots in the maize genome regulate the abundance of multiple, often metabolically related mass features. The utility of maize metabolite GWAS was demonstrated by confirming known benzoxazinoid biosynthesis genes, as well as by mapping isomeric variation in the accumulation of phenylpropanoid hydroxycitric acid esters to a single linkage block in a citrate synthase-like gene. Similar to gene expression databases, this metabolomic GWAS dataset constitutes an important public resource for linking maize metabolites with biosynthetic and regulatory genes.

genetics↗