Project description:With its 2.5 Mb DNA genome packed in amphora-shaped particles of bacterium-like dimension (1.2 µm in length, 0.5 µm in diameter), the Acanthamoeba-infecting Pandoravirus salinus remained the most spectacular and intriguing virus since its description in 2013. Following its isolation from shallow marine sediment off the coast of central Chile, that of its relative Pandoravirus dulcis from a fresh water pond near Melbourne, Australia, suggested that they were the first representatives of an emerging worldwide-distributed family of giant viruses. This was further suggested when P. inopinatum discovered in Germany, was sequenced in 2015. We now report the isolation and genome sequencing of three new strains (P. quercus, P.neocaledonia, P. macleodensis) from France, New Caledonia, and Australia. Using a combination of transcriptomic, proteomic, and bioinformatic analyses, we found that these six viruses share enough distinctive features to justify their classification in a new family, the Pandoraviridae, distinct from that of other large DNA viruses.
Project description:Pancreatic ductal adenocarcinoma (PDA) cells have a distinct dependence on de novo ornithine synthesis from glutamine via ornithine aminotransferase (OAT), which supports polyamine synthesis and is required for tumor growth. This directional OAT activity is normally largely restricted to infancy and contrasts with the reliance of most adult normal tissues and other cancer types on arginase (ARG) to generate arginine-derived ornithine, the substrate for polyamine synthesis. This dependence associates with arginine depletion in PDA tumor microenvironment, and is driven by mutant KRAS, which induces the expression of OAT and polyamine synthesis enzymes, including the rate-limiting enzyme ornithine decarboxylase-1 (ODC1). Loss of OAT, but not ARG2, largely mimics loss of ODC1, altering the transcriptional profiles in PDA cells, which in turn correlate with alterations in open chromatin states.
Project description:We describe a unique phenotype, blastulation failure, in three primary infertile males with oligoasthenoteratozoospermia (OAT) who underwent intracytoplasmic sperm injection (ICSI), resulting in multiple good-quality cleavage embryos that repeatedly failed to achieve blastulation or implantation. Single-cell analysis revealed that the arrested embryos had complex spermatozoa-derived chromosomal abnormalities, major embryonic genome activation failure, and overactivation of stress and apoptosis pathways at the transcriptional level. We further identified mutations in the meiosis-specific kinetochore factor MEIKIN gene in these males, causing OAT and chromosomal chaos in the spermatozoa. This study is the first to establish a connection between the genetic etiology of OAT and a novel embryo development arrest phenotype, indicating potenial risks of ICSI for OAT patients and providing a new explanation for recurrent implantation failure.
Project description:The goal was to measure the postprandial effect of an oat bran meal on gene expression in leukocytes from healthy subjects and to investigate the postprandial glucose, insulin and triglyceride responses. Linear mixed models were used for the array data to study the simultaneous dependency on many factors and functional categories of genes whose expression were correlated with oat bran intake were determined.
Project description:probiotics and prebiotics to maternal diets is related to decreased incidence of diarrhea and greater weight gain during lactation. Our objective was to determine the impact of adding whole ground oat as a prebiotic alone or in combination with postbiotic yeast culture (YC) (Saccharomyces cerevisiae) to sow gestation and lactation rations on milk composition, piglet growth, and incidence of post weaning diarrhea (PWD). Diets: control (CON), CON + yeast culture (YC) [5g/kg], CON + oat (15% inclusion rate) (Oat) or CON+ YC [5g/kg] + Oat (15%) were fed during the last 30 days of gestation and throughout lactation (18-21 days). Shotgun proteome analysis of day 4 and 7 postpartum milk samples found 36 differentially abundant proteins (P-adj <0.1) in both Oat and YC supplemented sows relative to CON. Notable was increased expression of antimicrobial proteins, lactoferrin and chitinase. IgG in milk of Oat supplemented sows was lower than YC supplemented sows (p<0.05) but had greater E. coli-antigen reactivity. Piglet weights at birth were similar. At weaning YC + Oat piglets weighed less and gained less weight (p<0.05) postweaning than CON. The incidence of PWD was lowest in the YC and Oat groups compared to CON and YC+ Oat groups. These data suggest that Oat or YC culture supplementation alters milk immune and antimicrobial associated proteins that can impact piglets but may have negative effects on piglet growth when given in combination.