The Desotamide Family of Antibiotics

Microbial natural products underpin the majority of antimicrobial compounds in clinical use and the discovery of new effective antibacterial treatments is urgently required to combat growing antimicrobial resistance. Non-ribosomal peptides are a major class of natural products to which many notable antibiotics belong. Recently, a new family of non-ribosomal peptide antibiotics were discovered—the desotamide family. The desotamide family consists of desotamide, wollamide, surugamide, ulleungmycin and noursamycin/curacomycin, which are cyclic peptides ranging in size between six and ten amino acids in length. Their biosynthesis has attracted significant attention because their highly functionalised scaffolds are cyclised by a recently identified standalone cyclase. Here, we provide a concise review of the desotamide family of antibiotics with an emphasis on their biosynthesis

A trans-acting cyclase off-loading strategy for non-ribosomal peptide synthetases

The terminal step in the biosynthesis of nonribosomal peptides is the hydrolytic release and, frequently, macrocyclization of an aminoacyl-S-thioester by an embedded thioesterase. The surugamide biosynthetic pathway is composed of two nonribosomal peptide synthetase (NRPS) assembly lines in which one produces surugamide A, which is a cyclic octapeptide, and the other produces surugamide F, a linear decapeptide. The terminal module of each system lacks an embedded thioesterase, which led us to question how the peptides are released from the assembly line (and cyclized in the case of surugamide A). We characterized a cyclase belonging to the β-lactamase superfamily in vivo, established that it is a trans-acting release factor for both compounds, and verified this functionality in vitro with a thioester mimic of linear surugamide A. Using bioinformatics, we estimate that ∼11% of filamentous Actinobacteria harbor an NRPS system lacking an embedded thioesterase and instead employ a trans-acting cyclase. This study improves the paradigmatic understanding of how nonribosomal peptides are released from the terminal peptidyl carrier protein and adds a new dimension to the synthetic biology toolkit

Freshwater shrimp (Palaemonetes australis) as a potential bioindicator of crustacean health

Palaemonetes australis is a euryhaline shrimp found in south-western Australian estuaries. To determine if P. australis is a suitable bioindicator species for monitoring the health of estuarine biota, they were exposed to measured concentrations of the polycyclic aromatic hydrocarbon, benzo[a]pyrene (B[a]P) at 0.01, 0.1 or 1 ppm for 14 days under laboratory conditions. At the end of exposure the shrimp were sacrificed for biomarker [ethoxycoumarin O-deethylase (ECOD), 8-oxo-dG concentration, and sorbitol dehydrogenase (SDH) activity] analyses. Gender did not appear to influence biomarker responses of the shrimp in this study. ECOD activity was induced in the treatment groups in a linear fashion from 3 (0.01 ppm) times to 12 (1 ppm) times the negative controls. 8-oxo-dG concentration was reduced 3 times in treatment groups below the controls suggesting impaired DNA repair pathways. There was no increase in SDH, signifying hepatopancreatic cell damage had not occurred in any treatment group. The response of P australis to B[a]P exposure indicates that this crustacean is suitable bioindicator species for both laboratory studies and field monitoring. A combination of ECOD and SDH activities and 8-oxo-dG concentration represent a suitable suite of biomarkers for environmental monitoring of the sublethal effects of organic pollution to crustaceans from an estuarine environment

A standalone β-ketoreductase acts concomitantly with biosynthesis of the antimycin scaffold

Antimycins are anticancer compounds produced by a hybrid nonribosomal peptide synthetase/polyketide synthase (NRPS/PKS) pathway. The biosynthesis of these compounds is well characterized, with the exception of the standalone β-ketoreductase enzyme AntM that is proposed to catalyze the reduction of the C8 carbonyl of the antimycin scaffold. Inactivation of antM and structural characterization suggested that rather than functioning as a post-PKS tailoring enzyme, AntM acts upon the terminal biosynthetic intermediate while it is tethered to the PKS acyl carrier protein. Mutational analysis identified two amino acid residues (Tyr185 and Phe223) that are proposed to serve as checkpoints controlling substrate access to the AntM active site. Aromatic checkpoint residues are conserved in uncharacterized standalone β-ketoreductases, indicating that they may also act concomitantly with synthesis of the scaffold. These data provide novel mechanistic insights into the functionality of standalone β-ketoreductases and will enable their reprogramming for combinatorial biosynthesis

A High Deuterium Abundance at z=0.7

Of the light elements, the primordial abundance of deuterium, (D/H)_p, provides the most sensitive diagnostic for the cosmological mass density parameter Omega_B. Recent high redshift (D/H) measurements are highly discrepant, although this may reflect observational uncertainties. The larger (D/H) values, which imply a low Omega_B and require the Universe to be dominated by non-baryonic matter (dynamical studies indicate a higher total density parameter), cause problems for galactic chemical evolution models since they have difficulty in reproducing the large decline down to the lower present-day (D/H). Conversely, low (D/H) values imply an Omega_B greater than derived from ^7Li and ^4He abundance measurements, and may require a deuterium abundance evolution that is too low to easily explain. Here we report the first measurement at intermediate redshift, where the observational difficulties are smaller, of a gas cloud with ideal characteristics for this experiment. Our analysis of the z = 0.7010 absorber toward 1718+4807 indicates (D/H) = 2.0 +/- 0.5 x 10^{-4} which is in the high range. This and other independent observations suggests there may be a cosmological inhomogeneity in (D/H)_p of at least a factor of ten.Comment: 6 pages, 1 figur

Constraining the magnetic field on white dwarf surfaces; Zeeman effects and fine structure constant variation

ABSTRACT White dwarf (WD) atmospheres are subjected to gravitational potentials around 105 times larger than occur on Earth. They provide a unique environment in which to search for any possible variation in fundamental physics in the presence of strong gravitational fields. However, a sufficiently strong magnetic field will alter absorption line profiles and introduce additional uncertainties in measurements of the fine structure constant. Estimating the magnetic field strength is thus essential in this context. Here, we model the absorption profiles of a large number of atomic transitions in the WD photosphere, including first-order Zeeman effects in the line profiles, varying the magnetic field as a free parameter. We apply the method to a high signal-to-noise, high-resolution, far-ultraviolet Hubble Space Telescope/Space Telescope Imaging Spectrograph spectrum of the WD G191−B2B. The method yields a sensitive upper limit on its magnetic field of B &amp;lt; 2300 G at the 3σ level. Using this upper limit, we find that the potential impact of quadratic Zeeman shifts on measurements of the fine structure constant in G191−B2B is 4 orders of magnitude below laboratory wavelength uncertainties.</jats:p

Mindlessness Revisited: Sequential Request Techniques Foster Compliance by Draining Self-control Resources

The present research extends previous findings suggesting that sequential request techniques, such as the Foot-in-the-Door (FITD) or Door-in-the-Face (DITF) technique, are primarily effective under conditions conducive of mindlessness. We forward that this mindlessness may be the product of the influence technique itself. More specifically, based on the notion of self-control as a limited resource, we hypothesize that actively responding to the initial request-phase of a FITD-compliance gaining procedure drains the target of his/her self-regulatory resources, thus creating the mindlessness so often observed in social influence settings. This resource depletion opens the door for compliance with the target request. The results were in line with these expectations. More specifically, we observed that active responding to an initial request of a FITD technique reduced the availability of self-regulatory resources. This state of resource depletion mediated the effect of the technique on behavioral compliance. In addition, the results of this study ruled out the alternate explanation that the effects were attributable to mood or a general tendency for acquiescence

Chronic inhibition, self-control and eating behavior: test of a 'resource depletion' model

The current research tested the hypothesis that individuals engaged in long-term efforts to limit food intake (e.g., individuals with high eating restraint) would have reduced capacity to regulate eating when self-control resources are limited. In the current research, body mass index (BMI) was used as a proxy for eating restraint based on the assumption that individuals with high BMI would have elevated levels of chronic eating restraint. A preliminary study (Study 1) aimed to provide evidence for the assumed relationship between eating restraint and BMI. Participants (N = 72) categorized into high or normal-range BMI groups completed the eating restraint scale. Consistent with the hypothesis, results revealed significantly higher scores on the weight fluctuation and concern for dieting subscales of the restraint scale among participants in the high BMI group compared to the normal-range BMI group. The main study (Study 2) aimed to test the hypothesized interactive effect of BMI and diminished self-control resources on eating behavior. Participants (N = 83) classified as having high or normal-range BMI were randomly allocated to receive a challenging counting task that depleted self-control resources (ego-depletion condition) or a non-depleting control task (no depletion condition). Participants then engaged in a second task in which required tasting and rating tempting cookies and candies. Amount of food consumed during the taste-and-rate task constituted the behavioral dependent measure. Regression analyses revealed a significant interaction effect of these variables on amount of food eaten in the taste-and-rate task. Individuals with high BMI had reduced capacity to regulate eating under conditions of self-control resource depletion as predicted. The interactive effects of BMI and self-control resource depletion on eating behavior were independent of trait self-control. Results extend knowledge of the role of self-control in regulating eating behavior and provide support for a limited-resource model of self-control. © 2013 Hagger et al

Gender specific factors associated with having stopped smoking among in-school adolescents in Ukraine: results from the Global Youth Tobacco Survey 2005

<p>Abstract</p> <p>Background</p> <p>The prevalence of cigarette smoking in Ukraine is different between genders and is among the highest in the world. There is need to identify gender-specific factors that are associated with having stopped smoking among adolescents.</p> <p>Findings</p> <p>We used data from the Ukraine Global Youth Tobacco Survey 2005. We carried out a backward stepwise logistic regression analysis with having stopped smoking as the outcome.</p> <p>Altogether, 2800 adolescents reported having ever smoked cigarettes. Overall 64.1% (63.4% male, and 65.5% female) adolescents reported having stopped smoking. Male adolescents who stated that smoking decreases body weight were 25% more likely, while female adolescents were 9% less likely to stop smoking. While male adolescents who received support on how to stop smoking from a family member were 7% less likely, female adolescents were 60% more likely to stop smoking. Furthermore, while male adolescents who received a lecture on the harmful effects of smoking were 10% less likely, female adolescents were 9% more likely to stop smoking. Finally both male and female adolescents who were sure or most probably that they would not smoke a cigarette offered to them by their best friends were more likely, and those adolescents who were sure that smoking is harmful to health were less likely to stop smoking.</p> <p>Conclusions</p> <p>Our study has identified some factors that are associated with having quit smoking that are gender-specific. We believe public health programs targeting adolescent smoking should consider these factors in their design and implementation of gender sensitive interventions.</p