Passive exposure to cannabidiol oil does not cause microbiome dysbiosis in larval zebrafish.

The use of cannabidiol oil derived products has dramatically increased in popularity and is predicted to grow steadily over the next decade. Given its relative stability, cannabidiol is likely to accumulate in the environment and affect aquatic animals and their host-associated microbiomes. Here, using zebrafish larvae, a model system in environmental toxicology, we show that passive exposure to a concentration as high as 200 µg/L cannabidiol oil did not affect larvae survival and had limited effects on their host-associated microbial communities. We found that the changes in community structure were limited to a decrease in two sequence variants identified as Methylobacterium-Methylorubrum sp. and one ASV identified as Staphylococcus sp., as well as the increase of one sequence variant identified as Chryseobacterium sp., a bacterium commensal to zebrafish. More importantly, we found that cannabidiol oil did not affect the overall richness and diversity of the exposed fish microbiomes. These results suggest that passive exposure to cannabidiol oil is unlikely to impact aquatic organisms in significant ways.

Cloning and heterologous expression of a novel subgroup of class IV polyhydroxyalkanoate synthase genes from the genus Bacillus.

Many microorganisms harbor genes necessary to synthesize biodegradable plastics known as polyhydroxyalkanoates (PHAs). We surveyed a genomic database and discovered a new cluster of class IV PHA synthase genes (phaRC). These genes are different in sequence and operon structure from any previously reported PHA synthase. The newly discovered PhaRC synthase was demonstrated to produce PHAs in recombinant Escherichia coli.

Ethanolamine Catabolism in Pseudomonas aeruginosa PAO1 Is Regulated by the Enhancer-Binding Protein EatR (PA4021) and the Alternative Sigma Factor RpoN.

UNLABELLED: Although genes encoding enzymes and proteins related to ethanolamine catabolism are widely distributed in the genomes of Pseudomonas spp., ethanolamine catabolism has received little attention among this metabolically versatile group of bacteria. In an attempt to shed light on this subject, this study focused on defining the key regulatory factors that govern the expression of the central ethanolamine catabolic pathway in Pseudomonas aeruginosa PAO1. This pathway is encoded by the PA4022-eat-eutBC operon and consists of a transport protein (Eat), an ethanolamine-ammonia lyase (EutBC), and an acetaldehyde dehydrogenase (PA4022). EutBC is an essential enzyme in ethanolamine catabolism because it hydrolyzes this amino alcohol into ammonia and acetaldehyde. The acetaldehyde intermediate is then converted into acetate in a reaction catalyzed by acetaldehyde dehydrogenase. Using a combination of growth analyses and ß-galactosidase fusions, the enhancer-binding protein PA4021 and the sigma factor RpoN were shown to be positive regulators of the PA4022-eat-eutBC operon in P. aeruginosa PAO1. PA4021 and RpoN were required for growth on ethanolamine, and both of these regulatory proteins were essential for induction of the PA4022-eat-eutBC operon. Unexpectedly, the results indicate that acetaldehyde (and not ethanolamine) serves as the inducer molecule that is sensed by PA4021 and leads to the transcriptional activation of the PA4022-eat-eutBC operon. Due to its regulatory role in ethanolamine catabolism, PA4021 was given the name EatR. Both EatR and its target genes are conserved in several other Pseudomonas spp., suggesting that these bacteria share a mechanism for regulating ethanolamine catabolism. IMPORTANCE: The results of this study provide a basis for understanding ethanolamine catabolism and its regulation in Pseudomonas aeruginosa PAO1. Interestingly, expression of the ethanolamine-catabolic genes in this bacterium was found to be under the control of a positive-feedback regulatory loop in a manner dependent on the transcriptional regulator PA4021, the sigma factor RpoN, and the metabolite acetaldehyde. Previously characterized regulators of ethanolamine catabolism are known to sense and respond directly to ethanolamine. In contrast, PA4021 (EatR) appears to monitor the intracellular levels of free acetaldehyde and responds through transcriptional activation of the ethanolamine-catabolic genes. This regulatory mechanism is unique and represents an alternative strategy used by bacteria to govern the acquisition of ethanolamine from their surroundings.

Towards a characterization of the structural determinants of specificity in the macrocyclizing thioesterase for deoxyerythronolide B biosynthesis.

Type I polyketide synthases (PKSs) are giant multidomain proteins that synthesize many therapeutics and other natural products. The synthesis proceeds by a thiotemplate mechanism whereby intermediates are covalently attached to the PKS. The release of the final polyketide is catalyzed by the terminal thioesterase (TE) domain through hydrolysis, transesterification, or macrocyclization. The PKS 6-deoxyerythronolide B synthase (DEBS) produces the 14-membered macrolide core of the clinically important antibiotic erythromycin. The TE domain of DEBS (DEBS TE) has well-established, empirically-defined specificities for hydrolysis or macrocyclization of native and modified substrates. We present efforts towards understanding the structural basis for the specificity of the thioesterase reaction in DEBS TE using a set of novel diphenyl alkylphosphonates, which mimic substrates that are specifically cyclized or hydrolyzed by DEBS TE. We have determined structures of a new construct of DEBS TE alone at 1.7Å, and DEBS TE bound with a simple allylphosphonate at 2.1Å resolution. Other, more complex diphenyl alkylphosphonates inhibit DEBS TE, but we were unable to visualize these faithful cyclization analogs in complex with DEBS TE. This work represents a first step towards using DEBS TE complexed with sophisticated substrate analogs to decipher the specificity determinants in this important reaction.

Chemically Intractable No More: In Vivo Incorporation of "Click"-Ready Fatty Acids into Poly-[(R)-3-hydroxyalkanoates] in Escherichia coli.

Poly-[(R)-3-hydroxyalkanoate] biopolymers, or PHAs, are biocompatible and biodegradable polyesters that can be produced by diverse microbial strains. PHA polymers have found widespread uses in applications ranging from sustainable replacements of nonbiodegradable bulk-commodity plastics to biomaterials. However, further expansion into other markets and industries has generally been limited by the inability to chemically modify these polymers. Recently, our lab engineered E. coli LSBJ, a microbial strain able to produce PHA copolymers with controlled unit compositions from simple and accessible fatty acid feedstocks. We envisioned meaningfully broadening the application spectrum of these materials via production of chemically tractable PHA biopolymers containing "click"-ready chemical functionalities. With a myriad of applications in mind, in this study we demonstrate the synthesis and biopolymerization of a panel of ω-azido fatty acids and take the first exploratory steps toward demonstrating their conjugation via a strain-promoted azide-alkyne cycloaddition (SPAAC) reaction. The convenience of accessing these materials will open the door to new applications for functionalized PHA polymers.

Non-canonical regioisomerizations and a 'Diels-Alderase' are likely essential in the biosynthesis of spiculoic acid A.

The regiochemistry of dehydration and cyclization steps of the linear biosynthetic precursor of the polyketide natural product Spiculoic acid A (1) were examined. Herein we describe the synthesis of polyene-containing aldehyde 21, a counterpart to the metabolite's putative polyketide intermediate and demonstrate its inability to undergo facile IMDA chemistry. These results suggest the involvement of a non-canonical regioisomerization in the biosynthesis of 1, and that the IMDA reaction is likely enzyme-catalyzed.

6-Deoxyerythronolide B synthase thioesterase-catalyzed macrocyclization is highly stereoselective.

Macrocyclic polyketide natural products are an indispensable source of therapeutic agents. The final stage of their biosynthesis, macrocyclization, is catalyzed regio- and stereoselectively by a thioesterase. A panel of substrates were synthesized to test their specificity for macrocyclization by the erythromycin polyketide synthase TE (DEBS TE) in vitro. It was shown that DEBS TE is highly stereospecific, successfully macrocyclizing a 14-member ring substrate with an R configured O-nucleophile, and highly regioselective, generating exclusively the 14-member lactone over the 12-member lactone.

Síndrome de epstein primer caso en la literatura nacional / Syndrome of epstein first case in of literature national

Presentamos el primer caso descrito en la literatura nacional de Síndrome de Epstein; el cual está caracterizado por la presencia de trombocitopatía de plaquetas gigantes, glomerulonefritis proliferativa (con hallazgos idénticos a la microscopia electrónica al Sindrome de Aiport) y sordera neurosensorial

Granulomatosis de wegner: presentación de un caso / Wegner's granulomatosis: report of a atypical case

La granulomatosis de Wegener es una patología infrecuente caracterizada por vasculitis necrotizante de vías aéreas superiores e inferiores y glomerulonefritis. El diagnóstico se realiza por la combinación de criterios clínicos, la biopsia del tejido afecto y la presencia de anticuerpos contra componentes extranucleares de neutrófilos. El pronóstico ha mejorado sustancialmente desde la introducción de la ciclofosfamida al tratamiento. Presentamos un caso atípico cuya clínica fue un síndrome febril prolongado, tos e insuficiencia renal rápidamente progresiva, sin lesión de vías respiratorias superiores

Hemoglobinopatía y riñón, estudio retrospectivo de la evaluación renal en 61 pacientes con hemoglobinopatías / Hemoglobinophathies and kidney, retrospective study of the renal evaluation in 61 patients with hemoglobinopathies

Se hizo un estudio de 61 historias en 93 pacientes controlados por enfermedades dreparocítica. Los pacientes presentan pérdida de la capacidad de concentración urinaria, densidad menor de 1010 (32%) y Osmolaridad urinaria menor de 400 mOsm/kgr de agua (100%), tanto en pacientes homocigotos como en las variantes de Hemoglobina SC, SF y ST. No se evidenció ningún caso de insuficiencia Renal Crónica pero sí de insuficiencia Renal Aguda (I.R.A.) en 10 pacientes, de los cuales 9 eran pacientes en estado terminal y uno presentaba Hepatitis B más I.R.A. La excreción urinaria de Potasio en 24 horas estaba disminuida en 9 (75%) de 12 mediciones efectuadas. La excreción de Sodio urinario en 24 horas fue normal en 12 de las 13 mediciones. Los electrolitos séricos fueron normales en 51 pacientes (85%). Estaban alterados, K: 8 pacientes, Na: 2 pacientes, Cl: 4 pacientes (todos estos valores presentes en los pacientes antes mencionados con I.R.A.)