53 research outputs found

    A novel gene cluster allows preferential utilization of fucosylated milk oligosaccharides in Bifidobacterium longum subsp. longum SC596

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    La microbiota intestinal infantil es a menudo colonizada por dos subespecies de Bifidobacterium longum: subsp. infantis (B. infantis) y subsp. longum (B. longum). El crecimiento competitivo de B. infantis en el intestino del neonato ha sido vinculado a la utilización de oligosacáridos (HMO) en la leche humana. Sin embargo, poco se sabe sobre cómo B. longum en el consumo de HMO. En este estudio, las cepas B. longum transmitidas mostraron diferentes fenotipos de crecimiento de HMO. Mientras que todas las cepas utilizadas eficientemente con lacto-N-tetraosa, focalizaron ciertas cepas, que, además, metabolizaron el HMO. El B. longum SC596 creció vigorosamente en el HMO, y la glycocaracterización reveló una preferencia por el consumo de HMO fucosilados. El transcriptomes SC596 durante la etapa temprana de crecimiento sobre HMO se asemeja más al crecimiento de la fucosilactosa, pasando más tarde a un patrón similar al crecimiento en el HMO neutro. El B. longum SC596 contiene un gen novedoso cerrado dedicado a la utilización de HMO fucosilado, incluyendo los genes para la importación de moléculas fucosiladas, metabolismo fucoso y dos α-fucosidasas. Este grupo mostró una inducción modular durante el crecimiento temprano de HMO y fucosilactosa. Este trabajo aclara el genoma y la variabilidad fisiológica del bebé portador de B. longum en el consumo de HMO, que se asemeja a B. infantis. La capacidad de consumir preferentemente HMO fucosilado sugiere una ventaja competitiva para estas singulares de las cepas de B. longum en el lactante alimentado con tripa.The infant intestinal microbiota is often colonized by two subspecies of Bifidobacterium longum: subsp. infantis (B. infantis) and subsp. longum (B. longum). Competitive growth of B. infantis in the neonate intestine has been linked to the utilization of human milk oligosaccharides (HMO). However, little is known how B. longum consumes HMO. In this study, infant-borne B. longum strains exhibited varying HMO growth phenotypes. While all strains efficiently utilized lacto-N-tetraose, certain strains additionally metabolized fucosylated HMO. B. longum SC596 grew vigorously on HMO, and glycoprofiling revealed a preference for consumption of fucosylated HMO. Transcriptomes of SC596 during early-stage growth on HMO were more similar to growth on fucosyllactose, transiting later to a pattern similar to growth on neutral HMO. B. longum SC596 contains a novel gene cluster devoted to the utilization of fucosylated HMO, including genes for import of fucosylated molecules, fucose metabolism and two α-fucosidases. This cluster showed a modular induction during early growth on HMO and fucosyllactose. This work clarifies the genomic and physiological variation of infant-borne B. longum to HMO consumption, which resembles B. infantis. The capability to preferentially consume fucosylated HMO suggests a competitive advantage for these unique B. longum strains in the breast-fed infant gut.• National Institutes of Health Awards AT007079, HD065122 y AT008759 • Peter J. Shields Endowed Chair in Dairy Food Science • Conicyt Fondecyt: Beca de iniciación 11130518 • Ministerio de Educación y Ciencia y Universidad de Extremadura.peerReviewe

    Chemical Approaches To Perturb, Profile, and Perceive Glycans

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    Glycosylation is an essential form of post-translational modification that regulates intracellular and extracellular processes. Regrettably, conventional biochemical and genetic methods often fall short for the study of glycans, because their structures are often not precisely defined at the genetic level. To address this deficiency, chemists have developed technologies to perturb glycan biosynthesis, profile their presentation at the systems level, and perceive their spatial distribution. These tools have identified potential disease biomarkers and ways to monitor dynamic changes to the glycome in living organisms. Still, glycosylation remains the underexplored frontier of many biological systems. In this Account, we focus on research in our laboratory that seeks to transform the study of glycan function from a challenge to routine practice

    Milk Glycans and Their Interaction with the Infant-Gut Microbiota

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    Human milk is a unique and complex fluid that provides infant nutrition and delivers an array of bioactive molecules that serve various functions. Glycans, abundant in milk, can be found as free oligosaccharides or as glycoconjugates. Milk glycans are increasingly linked to beneficial outcomes in neonates through protection from pathogens and modulation of the immune system. Indeed, these glycans influence the development of the infant and the infant-gut microbiota. Bifidobacterium species commonly are enriched in breastfed infants and are among a limited group of bacteria that readily consume human milk oligosaccharides (HMOs) and milk glycoconjugates. Given the importance of bifidobacteria in infant health, numerous studies have examined the molecular mechanisms they employ to consume HMOs and milk glycans, thus providing insight into this unique enrichment and shedding light on a range of translational opportunities to benefit at-risk infants

    “My bladder is hanging out of my anus”: Successful Management of First Reported Case of Male Transanal Bladder Prolapse

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    We present a case of an 81-year-old man who presented with a large recto-urethral fistula resulting in prolapsing bladder through the anus. A multi-disciplinary approach with urology, colorectal surgery and plastic surgery was utilized for management of the prolapse with excellent postoperative result. This unique scenario enabled a transanal cystoprostatectomy; the procedure was completed using a natural orifice without transabdominal surgery

    Neuronal ER-plasma membrane junctions couple excitation to Ca2+-activated PKA signaling

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    Abstract Junctions between the endoplasmic reticulum (ER) and the plasma membrane (PM) are specialized membrane contacts ubiquitous in eukaryotic cells. Concentration of intracellular signaling machinery near ER-PM junctions allows these domains to serve critical roles in lipid and Ca2+ signaling and homeostasis. Subcellular compartmentalization of protein kinase A (PKA) signaling also regulates essential cellular functions, however, no specific association between PKA and ER-PM junctional domains is known. Here, we show that in brain neurons type I PKA is directed to Kv2.1 channel-dependent ER-PM junctional domains via SPHKAP, a type I PKA-specific anchoring protein. SPHKAP association with type I PKA regulatory subunit RI and ER-resident VAP proteins results in the concentration of type I PKA between stacked ER cisternae associated with ER-PM junctions. This ER-associated PKA signalosome enables reciprocal regulation between PKA and Ca2+ signaling machinery to support Ca2+ influx and excitation-transcription coupling. These data reveal that neuronal ER-PM junctions support a receptor-independent form of PKA signaling driven by membrane depolarization and intracellular Ca2+, allowing conversion of information encoded in electrical signals into biochemical changes universally recognized throughout the cell
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