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

Functional Characteristics of a Highly Specific Integrase Encoded by an LTR-Retrotransposon

Background: The retroviral Integrase protein catalyzes the insertion of linear viral DNA into host cell DNA. Although different retroviruses have been shown to target distinctive chromosomal regions, few of them display a site-specific integration. ZAM, a retroelement from Drosophila melanogaster very similar in structure and replication cycle to mammalian retroviruses is highly site-specific. Indeed, ZAM copies target the genomic 59-CGCGCg-39 consensus-sequences. To enlighten the determinants of this high integration specificity, we investigated the functional properties of its integrase protein denoted ZAM-IN. Principal Findings: Here we show that ZAM-IN displays the property to nick DNA molecules in vitro. This endonuclease activity targets specific sequences that are present in a 388 bp fragment taken from the white locus and known to be a genomic ZAM integration site in vivo. Furthermore, ZAM-IN displays the unusual property to directly bind specific genomic DNA sequences. Two specific and independent sites are recognized within the 388 bp fragment of the white locus: the CGCGCg sequence and a closely apposed site different in sequence. Conclusion: This study strongly argues that the intrinsic properties of ZAM-IN, ie its binding properties and its endonuclease activity, play an important part in ZAM integration specificity. Its ability to select two binding sites and to nick the DNA molecule reminds the strategy used by some site-specific recombination enzymes and forms the basis for site-specifi

Conservation, Variability and the Modeling of Active Protein Kinases

The human proteome is rich with protein kinases, and this richness has made the kinase of crucial importance in initiating and maintaining cell behavior. Elucidating cell signaling networks and manipulating their components to understand and alter behavior require well designed inhibitors. These inhibitors are needed in culture to cause and study network perturbations, and the same compounds can be used as drugs to treat disease. Understanding the structural biology of protein kinases in detail, including their commonalities, differences and modes of substrate interaction, is necessary for designing high quality inhibitors that will be of true use for cell biology and disease therapy. To this end, we here report on a structural analysis of all available active-conformation protein kinases, discussing residue conservation, the novel features of such conservation, unique properties of atypical kinases and variability in the context of substrate binding. We also demonstrate how this information can be used for structure prediction. Our findings will be of use not only in understanding protein kinase function and evolution, but they highlight the flaws inherent in kinase drug design as commonly practiced and dictate an appropriate strategy for the sophisticated design of specific inhibitors for use in the laboratory and disease therapy

Feasibility of a randomised trial of a continuing medical education program in shared decision-making on the use of antibiotics for acute respiratory infections in primary care: the DECISION+ pilot trial

Abstract Background The misuse and limited effectiveness of antibiotics for acute respiratory infections (ARIs) are well documented, and current approaches targeting physicians or patients to improve appropriate use have had limited effect. Shared decision-making could be a promising strategy to improve appropriate antibiotic use for ARIs, but very little is known about its implementation processes and outcomes in clinical settings. In this matter, pilot studies have played a key role in health science research over the past years in providing information for the planning, justification, and/or refinement of larger studies. The objective of our study was to assess the feasibility and acceptability of the study design, procedures, and intervention of the DECISION+ program, a continuing medical education program in shared decision-making among family physicians and their patients on the optimal use of antibiotics for treating ARIs in primary care. Methods A pilot clustered randomised trial was conducted. Family medicine groups (FMGs) were randomly assigned, to either the DECISION+ program, which included three 3-hour workshops over a four- to six-month period, or a control group that had a delayed exposure to the program. Results Among 21 FMGs contacted, 5 (24%) agreed to participate in the pilot study. A total of 39 family physicians (18 in the two experimental and 21 in the three control FMGs) and their 544 patients consulting for an ARI were recruited. The proportion of recruited family physicians who participated in all three workshops was 46% (50% for the experimental group and 43% for the control group), and the overall mean level of satisfaction regarding the workshops was 94%. Conclusions This trial, while aiming to demonstrate the feasibility and acceptability of conducting a larger study, has identified important opportunities for improving the design of a definitive trial. This pilot trial is informative for researchers and clinicians interested in designing and/or conducting studies with FMGs regarding training of physicians in shared decision-making. Trial Registration Clinicaltrials.Gov NCT0035431

The Explosion Mechanism of Core-Collapse Supernovae and Its Observational Signatures

The death of massive stars is shrouded in many mysteries. One of them is the mechanism that overturns the collapse of the degenerate iron core into an explosion, a process that determines the supernova explosion energy, properties of the surviving compact remnant, and the nucleosynthetic yields. The number of core-collapse supernova observations has been growing with an accelerating pace thanks to modern time-domain astronomical surveys and new tests of the explosion mechanism are becoming possible. We review predictions of parameterized supernova explosion models and compare them with explosion properties inferred from observed light curves, spectra, and neutron star masses.Comment: Reviews in Frontiers of Modern Astrophysics; From Space Debris to Cosmology, edited by Kab\'ath, Petr; Jones, David; Skarka, Marek. ISBN: 978-3-030-38509-5. Cham: Springer International Publishing, 2020, pp. 189-21

Experimental measurement of specific impulse distribution and transient deformation of plates subjected to near-field explosive blasts

The shock wave generated from a high explosive detonation can cause significant damage to any objects that it encounters, particularly those objects located close to the source of the explosion. Understanding blast wave development and accurately quantifying its effect on structural systems remains a considerable challenge to the scientific community. This paper presents a comprehensive experimental study into the loading acting on, and subsequent deformation of, targets subjected to near-field explosive detonations. Two experimental test series were conducted at the University of Sheffield (UoS), UK, and the University of Cape Town (UCT), South Africa, where blast load distributions using Hopkinson pressure bars and dynamic target deflections using digital image correlation were measured respectively. It is shown through conservation of momentum and Hopkinson-Cranz scaling that initial plate velocity profiles are directly proportional to the imparted impulse distribution, and that spatial variations in loading as a result of surface instabilities in the expanding detonation product cloud are significant enough to influence the transient displacement profile of a blast loaded plate

Effects of endocrine disrupting chemicals on expression of phospholipid hydroperoxide glutathione peroxidase mRNA in rat testes

Phospholipid hydroperoxide glutathione peroxidase (PHGPx), an antioxidative selenoprotein, is modulated by estrogen in the testis and oviduct. To examine whether potential endocrine disrupting chemicals (EDCs) affect the microenvironment of the testes, the expression patterns of PHGPx mRNA and histological changes were analyzed in 5-week-old Sprague-Dawley male rats exposed to several EDCs such as an androgenic compound [testosterone (50, 200, and 1,000 µg/kg)], anti-androgenic compounds [flutamide (1, 5, and 25 mg/kg), ketoconazole (0.2 and 1 mg/kg), and diethylhexyl phthalate (10, 50, and 250 mg/kg)], and estrogenic compounds [nonylphenol (10, 50, 100, and 250 mg/kg), octylphenol (10, 50, and 250 mg/kg), and diethylstilbestrol (10, 20, and 40 µg/kg)] daily for 3 weeks via oral administration. Mild proliferation of germ cells and hyperplasia of interstitial cells were observed in the testes of the flutamide-treated group and deletion of the germinal epithelium and sloughing of germ cells were observed in testes of the diethylstilbestrol-treated group. Treatment with testosterone was shown to slightly decrease PHGPx mRNA levels in testes by the reverse transcriptionpolymerase chain reaction. However, anti-androgenic compounds (flutamide, ketoconazole, and diethylhexyl phthalate) and estrogenic compounds (nonylphenol, octylphenol, and diethylstilbestrol) significantly upregulated PHGPx mRNA in the testes (p < 0.05). These findings indicate that the EDCs might have a detrimental effect on spermatogenesis via abnormal enhancement of PHGPx expression in testes and that PHGPx is useful as a biomarker for toxicity screening of estrogenic or antiandrogenic EDCs in testes