Reshaping commensal gut microbiota in early life with amoxicillin presents with lower blood pressure
Contributors: Saroj Chakraborty
... Pediatric hypertension is recognized as an emerging global health concern. While new guidelines are developed for facilitating clinical management, the reasons for the prevalence of hypertension in children remain unknown. Genetics and environmental factors do not fully account for the growing incidence of pediatric hypertension. Because stable bacterial flora in early life are linked with health outcomes later in life, we hypothesized that reshaping of gut microbiota in early developmental stages of life affects blood pressure (BP) of pediatric subjects. To test this hypothesis, we administered amoxicillin, the most commonly prescribed pediatric antibiotic, to alter gut microbiota of young, genetically hypertensive rats (study 1) and dams during gestation and lactation to reshape microbiota of offspring (study 2). Reshaping of microbiota, with reductions in Firmicutes/Bacteriodetes ratio observed in Amoxicillin treated young rats and in dams. Amoxicillin treated rats also had lower blood pressure compared to the untreated rats. In the young rats treated with amoxicillin, the lowering effect on blood pressure persisted even after the antibiotics were discontinued. Similarly, the offspring from the dams treated with amoxicillin also showed lower systolic blood pressure compared to the control rats. Remarkably, in all cases, a decrease in BP was associated with lowering of Veillonellaceae, which are succinate-producing bacteria. Elevated plasma succinate is reported in hypertension. Accordingly, serum succinate was measured and found lower in animals treated with amoxicillin. Our results demonstrate a direct correlation between succinate-producing gut microbiota and early development of hypertension, and indicate that reshaping gut microbiota, especially by depleting succinate-producing microbiota early in life may have long-term benefits for hypertension-prone individuals.
Contributors: Young-Min Soh, Iain Finley Davidson, Stefano Zamuner, Jerome Basquin, Michael Taschner, Florian Patrick Bock, Jan-Willem Veening, Paolo De Los Rios, Jan-Michael Peters, Stephan Gruber
... Dracala spotting assay, ITC measurements, Malachite Green Assay, in vitro and in vivo crosslinking , DNA loading assay, Sequence alignment used for DCA, Single Molecule Imaging
Contributors: Won Kim, Maria Rendon, Jeanine McLean, David Trees, Magdalene So
... Fasta (quiver) and gff.gz files generated from PacBio Single Molecule, Real-Time sequencing of Neisseria elongata chromosome. Overview Excel file contains base calling accuracy and quality of sequencing reads. These data were used to determine methylated sequence motifs in Neisseria elongata (Table S5).
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Contributors: Gil Sharon
... Raw data (excluding raw sequencing and metabolomic data) used to construct figures for manuscript. Data is predominantly in csv or tsv format. qza and qzv files are QIIME2 outputs and can be viewed at https://view.qiime2.org/ . mat files are mat lab datasets. Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice Gil Sharon1,*, Nikki Jamie Cruz1, Dae-Wook Kang2,3,21, Michael J. Gandal4,5,6,7, Bo Wang1, Young-Mo Kim8, Erika M. Zink8, Cameron P. Casey8, Bryn C. Taylor9, Christianne J. Lane10, Lisa M. Bramer11, Nancy G. Isern8, David W. Hoyt8, Cecilia Noecker12, Michael J. Sweredoski1, Annie Moradian1, Elhanan Borenstein12,13,14,15,16, Janet K. Jansson8, Rob Knight17,18,19, Thomas O. Metz8, Carlos Lois1, Daniel H. Geschwind4,5,6, Rosa Krajmalnik-Brown2,3, and Sarkis K. Mazmanian1,20,* Autism spectrum disorder (ASD) manifests as alterations in complex human behaviors including social communication and stereotypies. In addition to genetic risks, the gut microbiome differs between typically-developing (TD) and ASD individuals, though it remains unclear whether the microbiome contributes to symptoms. We transplanted gut microbiota from human donors with ASD and TD controls into germ-free mice, and reveal that colonization with ASD microbiota was sufficient to induce hallmark autistic behaviors. The brains of mice colonized with ASD microbiota display alternative splicing of ASD-relevant genes. Microbiome and metabolome profiles of mice harboring human microbiota predict that specific bacterial taxa and their metabolites modulate ASD behaviors. Indeed, treatment of an ASD mouse model with candidate microbial metabolites improves behavioral abnormalities and affects neuronal excitability in the brain. We propose that the gut microbiome modulates behaviors in mice via production of neuroactive metabolites, suggesting that gut-brain connections contribute to the pathophysiology of ASD.
Data for: Structural modifications of 2,3-indolobetulinic acid: design and synthesis of highly potent α-glucosidase inhibitors
Contributors: Elmira Khusnutdinova, Thi Tu Anh Le, Tra Nguyen Thanh, Anastasiya V. Petrova, Denis Babkov, Oxana Kazakova, Ha Nguyen Thi Thu, Cham Ba Thi
... A series of nineteen nitrogen-containing lupane triterpenoids was obtained by modification of C2, C3, C20 and C28 positions of betulonic acid and their α-glucosidase inhibiting activity was investigated. Being a leader compound from our previous study, 2,3-indolo-betulinic acid was used as the main template for different modifications at C-(28)-carboxyl group to obtain cyano-, methylcyanoethoxy-, propargyloxy- and carboxamide derivatives. 20-Oxo- and 29-hydroxy-20-oxo-30-nor-analogues of 2,3-indolo-betulinic acid were synthesized by ozonolysis of betulonic acid followed by Fischer indolization reaction. To compare the influence of the fused indole or the seven membered A-ring on the inhibitory activity, lupane A-azepanones with different substituents at C28 were synthesized. The structure-activity relationships revealed that the enzyme inhibition activity dramatically increased (up to 4730 times) when the carboxylic group of 2,3-indolo-betulinic acid was сonverted to the corresponding amide. Thus, the IC50 values for glycine amide and L-phenylalanine amides were 0.04 and 0.05 μM, respectively. This study also revealed that 2,3-indolo-platanic acid is 4.5 times more active than the parent triterpenoid with IC50 of 0.4 μM. Molecular modeling suggested that improved potency is due to additional polar interactions formed between C28 side chain and a sub-pocket of the α-glucosidase allosteric site.
Contributors: Jiaming Qi
... Whole-genome sequencing of Bacillus subtilis BS-6. Leading Bio-agricultural Co., Ltd.
Essential gene profiles for human pluripotent stem cells identify uncharacterized genes and substrate dependencies. Mair et al.
Contributors: Barbara Mair, Jelena Tomic, Sanna Masud, Jason Moffat
... Human pluripotent stem cells (hPSCs) provide an invaluable tool for modeling diseases and hold promise for regenerative medicine. For understanding pluripotency and lineage differentiation mechanisms, a critical first step involves systematically cataloging genes that are indispensable for hPSC maintenance and proliferation. To map genetic determinants of hPSC fitness, we performed genome-scale loss-of-function screens in an inducible Cas9 H1 hPSC line cultured on feeder cells and feeder-free to identify essential genes. Among these, we found FOXH1 and VENTX, genes that encode transcription factors previously implicated in stem cell biology, as well as an uncharacterized gene, C22orf43/DRICH1. hPSCs essential genes are substantially different from other cell lines, and gene essentiality in hPSCs is highly context-dependent with respect to different growth substrates. Our CRISPR screens establish parameters for genome-wide screens in hPSCs, which will facilitate the characterization of unappreciated regulators of hPSC biology to understand the genetic wiring of hPSC fitness and pluripotency.
CRISPR/Cas9 deletions in a conserved exon of Distal-less generates gains and losses in a recently acquired morphological novelty in flies.
Contributors: Gowri rajaratnam
... This dataset contains the aligned fasta seqeuncing files used for characterising the CRISPR/Cas9 mutations in all mutants mentioned in the paper. It also contains the processed isoform sequencing files as well as the Mass Spectometry output for the protein sequencing experiment.
The diversity, structure and function of heritable adaptive immunity sequences in the Aedes aegypti genome
Contributors: Zachary Whitfield
... Datasets associated with Whitfield, Dolan, Kunitomi et al., "The diversity, structure and function of heritable adaptive immunity sequences in the Aedes aegypti genome". See methods for description of individual files. Aag2_Contigs.fa is the fasta form of the analyzed genome with updated IDs more compatible with the uploaded bed files.
Contributors: Ervin Fodor
... See Serna Martin et al Mol Cell 70, 1101-1110, 2018 for the description of data.