The Hybrid Antibiotic Thiomarinol A Overcomes Intrinsic Resistance in Using a Privileged Dithiolopyrrolone Moiety.

An impermeable outer membrane and multidrug efflux pumps work in concert to provide Gram-negative bacteria with intrinsic resistance against many antibiotics. These resistance mechanisms reduce the intracellular concentrations of antibiotics and render them ineffective. The natural product thiomarinol A combines holothin, a dithiolopyrrolone antibiotic, with marinolic acid A, a close analogue of mupirocin.

Enzymatic Synthesis of Diverse Heterocycles by a Noncanonical Nonribosomal Peptide Synthetase.

Nonribosomal peptide synthetases (NRPSs) are typically multimodular enzymes that assemble amino acids or carboxylic acids into complex natural products. Here, we characterize a monomodular NRPS, PvfC, encoded by the () gene cluster that is essential for virulence and signaling in different bacterial species. PvfC exhibits a unique adenylation-thiolation-reductase (ATR) domain architecture that is understudied in bacteria.

Pseudomonas Virulence Factor Pathway Synthesizes Autoinducers That Regulate the Secretome of a Pathogen.

Cell-to-cell communication via chemical signals is an essential mechanism that pathogenic bacteria use to coordinate group behaviors and promote virulence. The () gene cluster is distributed in more than 500 strains of proteobacteria including both plant and human pathogens. The cluster has been implicated in the production of signaling molecules important for virulence; however, the regulatory impact of these signaling molecules on virulence had not been elucidated.

In Vitro Reconstitution Reveals a Central Role for the N-Oxygenase PvfB in (Dihydro)pyrazine-N-oxide and Valdiazen Biosynthesis.

The Pseudomonas virulence factor (pvf) operon is essential for the biosynthesis of two very different natural product scaffolds: the (dihydro)pyrazine-N-oxides and the diazeniumdiolate, valdiazen. PvfB is a member of the non-heme diiron N-oxygenase enzyme family that commonly convert anilines to their nitroaromatic counterparts. In contrast, we show that PvfB catalyzes N-oxygenation of the α-amine of valine, first to the hydroxylamine and then the nitroso, while linked to the carrier protein of PvfC.

Specificity of Nonribosomal Peptide Synthetases in the Biosynthesis of the .

The () biosynthetic operon has been implicated in bacterial virulence and signaling. We identified 308 bacterial strains containing homologues that likely produce signaling molecules with distinct structures and biological activities. Several homologues of the nonribosomal peptide synthetase (NRPS), PvfC, were biochemically characterized and shown to activate l-Val or l-Leu.

Management of post-myocardial infarction ventricular septal defects: A critical assessment.

Background: Post-myocardial infarction (MI) ventricular septal defects (PIVSD) are an uncommon but life-threatening complication of acute MI. Although surgical closure has been the standard of care, mortality, and recurrence of VSD remain high even after emergent surgery. Transcatheter VSD closure (TCC) devices have become an alternative or adjunct to surgical closure.

Discovery of (Dihydro)pyrazine N-Oxides via Genome Mining in Pseudomonas.

Overexpression of the Pseudomonas virulence factor ( pvf) biosynthetic operon led to the identification of a family of pyrazine N-oxides (PNOs), including a novel dihydropyrazine N,N'-dioxide (dPNO) metabolite. The nonribosomal peptide synthetase responsible for production of (d)PNOs was characterized, and a biosynthetic pathway for (d)PNOs was proposed. This work highlights the unique chemistry catalyzed by pvf-encoded enzymes and sets the stage for bioactivity studies of the metabolites produced by the virulence pathway.

The neutron imaging diagnostic at NIF (invited).

A neutron imaging diagnostic has recently been commissioned at the National Ignition Facility (NIF). This new system is an important diagnostic tool for inertial fusion studies at the NIF for measuring the size and shape of the burning DT plasma during the ignition stage of Inertial Confinement Fusion (ICF) implosions. The imaging technique utilizes a pinhole neutron aperture, placed between the neutron source and a neutron detector.

Neutron spectrometry--an essential tool for diagnosing implosions at the National Ignition Facility (invited).

DT neutron yield (Y(n)), ion temperature (T(i)), and down-scatter ratio (dsr) determined from measured neutron spectra are essential metrics for diagnosing the performance of inertial confinement fusion (ICF) implosions at the National Ignition Facility (NIF). A suite of neutron-time-of-flight (nTOF) spectrometers and a magnetic recoil spectrometer (MRS) have been implemented in different locations around the NIF target chamber, providing good implosion coverage and the complementarity required for reliable measurements of Y(n), T(i), and dsr. From the measured dsr value, an areal density (ρR) is determined through the relationship ρR(tot) (g∕cm(2)) = (20.

Modeling the National Ignition Facility neutron imaging system.

Numerical modeling of the neutron imaging system for the National Ignition Facility (NIF), forward from calculated target neutron emission to a camera image, will guide both the reduction of data and the future development of the system. Located 28 m from target chamber center, the system can produce two images at different neutron energies by gating on neutron arrival time. The brighter image, using neutrons near 14 MeV, reflects the size and symmetry of the implosion "hot spot.

Clinical observations, biochemical data, and postmortem and histopathologic findings in young dairy calves fed zeolite clinoptilolite binder combined with milk replacer.

Objective: To identify any adverse effects on health or performance in young dairy calves fed clinoptilolite mixed with milk replacer.

Animals: 26 male Holstein calves (1 to 7 days old).

Procedures: Twice daily for 28 days, calves were fed milk replacer with no clinoptilolite (control group; n=8), 0.

A spatially resolved ion temperature diagnostic for the National Ignition Facility.

The concepts and initial development efforts for a spatially resolved ion temperature diagnostic are described. The diagnostic is intended for Inertial Confinement Fusion experiments at the National Ignition Facility and is an integration of neutron aperture imaging and ion temperature techniques. The neutron imaging technique is extended by recording tomographic projections of the radiation-to-light converter on a streak camera.

The National Ignition Facility neutron imaging system.

The National Ignition Facility (NIF) is scheduled to begin deuterium-tritium (DT) shots possibly in the next several years. One of the important diagnostics in understanding capsule behavior and to guide changes in Hohlraum illumination, capsule design, and geometry will be neutron imaging of both the primary 14 MeV neutrons and the lower-energy downscattered neutrons in the 6-13 MeV range. The neutron imaging system (NIS) described here, which we are currently building for use on NIF, uses a precisely aligned set of apertures near the target to form the neutron images on a segmented scintillator.

RNA silencing-mediated resistance to a crinivirus (Closteroviridae) in cultivated sweet potato (Ipomoea batatas L.) and development of sweet potato virus disease following co-infection with a potyvirus.

Sweet potato chlorotic stunt virus (SPCSV; genus Crinivirus, family Closteroviridae) is one of the most important pathogens of sweet potato (Ipomoea batatas L.). It can reduce yields by 50% by itself and cause various synergistic disease complexes when co-infecting with other viruses, including sweet potato feathery mottle virus (SPFMV; genus Potyvirus, family Potyviridae).

Development of teaser bulls under field conditions.

A teaser bull is a term describing a bull whose reproductive system has been surgically altered to render him sterile. The purpose of such bulls is to aid in detection of cows in estrus to facilitate when to artificially inseminate. The bull is sterilized by either vasectomy or caudal epididymectomy.

A comparison of two combinations of xylazine-ketamine administered intramuscularly to alpacas and of reversal with tolazoline.

Objective: To evaluate the anesthetic and cardiorespiratory effects of two doses of intramuscular (IM) xylazine/ketamine in alpacas, and to determine if tolazoline would reduce the anesthetic recovery time.

Study Design: Prospective randomized crossover study.

Animals: Six castrated male alpacas.

Shock temperature measurement using neutron resonance spectroscopy.

We report a direct measurement of temperature in a shocked metal using Doppler broadening of neutron resonances. The 21.1-eV resonance in 182W was used to measure the temperature in molybdenum shocked to approximately 63 GPa.

A comparison of two intramuscular doses of xylazine-ketamine combination and tolazoline reversal in llamas.

Objective: To evaluate the anesthetic and cardiorespiratory effects of two doses of intramuscular xylazine/ketamine in llamas, and to determine if an intramuscular injection of tolazoline would shorten the anesthesia recovery time.

Study Design: Prospective randomized study.

Animals: Six castrated male llamas.

Influence of estradiol, progesterone, and nutrition on concentrations of gonadotropins and GnRH receptors, and abundance of mRNA for GnRH receptors and gonadotropin subunits in pituitary glands of beef cows.

Nutritionally induced anovulatory cows (n = 28) were used to determine the effect of steroids on regulation of synthesis and secretion of gonadotropins. Anovulatory cows were ovariectomized and received intravaginal inserts containing estradiol (E2), progesterone (P4), E2 and P4 (E2P4), or a sham intravaginal insert (C) for 7 d. Concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were quantified in serum and E2 and P4 were quantified in plasma.

Influence of exogenous gonadotropin-releasing hormone on ovarian function in beef cows after short- and long-term nutritionally induced anovulation.

The effect of pulsatile infusion of gonadotropin-releasing hormone (GnRH) on follicular function was evaluated in nutritionally induced anovulatory beef cows. After 4 (short; n = 12) or 18 wk (long; n = 12) of anovulation, cows were randomly assigned within anovulatory group to either 2 microg of GnRH treatment or saline (control; i.v.

Seasonal effects on estrous behavior and time of ovulation in nonlactating beef cows.

Estrous behavior and time of ovulation relative to the onset of estrus were determined in mature Angus x Hereford cows (n = 17 to 21 each season) during summer, winter, and spring for 2 yr. Estrous behavior was evaluated during the first of two consecutive estrous periods, and time of ovulation was determined during the second estrus. Concentrations of progesterone were quantified in twice weekly blood samples to ensure all cows had normal estrous cycles.

Expression patterns of retinoid X receptors, retinaldehyde dehydrogenase, and peroxisome proliferator activated receptor gamma in bovine preattachment embryos.

In cattle, administration of retinol at the time of superovulation has been indirectly associated with enhanced developmental potential of the embryo. Vitamin A and its metabolites influence several developmental processes by interacting with 2 different types of nuclear receptors, retinoic acid receptors and retinoid X receptors (RXRs). Given the limited information available concerning the RXR-mediated retinoid signaling system, particularly in species other than rodents, this study was performed to gain insight into the potential role of retinoid signaling during preattachment embryo development in the cow.

Expression of retinol-binding protein messenger RNA and retinoic acid receptors in preattachment bovine embryos.

In cattle, retinoic acid (RA) has been indirectly associated with developmental potential of the embryo. RA is transported by retinol-binding protein (RBP) and actions of RA are mediated by several subtypes of nuclear retinoic acid receptors (RAR). Bovine embryos, produced in vitro from oocytes harvested from ovaries collected at a local abattoir, were frozen in liquid nitrogen at the oocyte, 2-, 4-, 8-, 16 to 20-cell, morula, blastocyst, and hatched blastocyst stages.