Monitoring winter and summer abundance of cetaceans in the Pelagos Sanctuary (northwestern Mediterranean Sea) through aerial surveys

Systematic long-term monitoring of abundance is essential to inform conservation measures and evaluate their effectiveness. To instigate such work in the Pelagos Sanctuary in the Mediterranean, two aerial surveys were conducted in winter and summer 2009. A total of 467 (131 in winter, 336 in summer) sightings of 7 species was made. Sample sizes were sufficient to estimate abundance of fin whales in summer (148; 95% CI = 87–254) and striped dolphins in winter (19,462; 95% CI = 12 939–29 273) and in summer (38 488; 95% CI = 27 447–53 968). Numbers of animals within the Sanctuary are significantly higher in summer, when human activities and thus potential population level impacts are highest. Comparisons with data from past shipboard surveys suggest an appreciable decrease in fin whales within the Sanctuary area and an appreciable increase in striped dolphins. Aerial surveys proved to be more efficient than ship surveys, allowing more robust estimates, with smaller CIs and CVs. These results provide essential baseline data for this marine protected area and continued regular surveys will allow the effectiveness of the MPA in terms of cetacean conservation to be evaluated and inform future management measures. The collected data may also be crucial in assessing whether ship strikes, one of the main causes of death for fin whales in the Mediterranean, are affecting the Mediterranean population.     

Fibrinogen alters mouse brain endothelial cell layer integrity affecting vascular endothelial cadherin

Many inflammatory diseases are associated with elevated blood concentration of fibrinogen (Fg) leading to vascular dysfunction. We showed that pathologically high (4 mg/ml) content of Fg disrupts integrity of endothelial cell (EC) layer and causes macromolecular leakage affecting tight junction proteins. However, role of adherence junction proteins, particularly vascular endothelial cadherin (VE-cadherin) and matrix metalloproteinase-9 (MMP-9) in this process is not clear. We tested the hypothesis that at high levels Fg affects integrity of mouse brain endothelial cell (MBEC) monolayer through activation of MMP-9 and downregulation of VE-cadherin expression and in part its translocation to the cytosol.The effect of Fg on cultured MBEC layer integrity was assessed by measuring transendothelial electrical resistance. Cellular expression and translocation of VE-cadherin were assessed by Western blot and immunohistochemical analyses, (respectively). Our results suggest that high content of Fg decreased VE-cadherin expression at protein and mRNA levels. Fg induced translocation of VE-cadherin to cytosol, which led to disruption of cell-to-cell interaction and cell to subendothelial matrix attachment. Fg-induced alterations in cell layer integrity and their attachment were diminished during inhibition of MMP-9 activity.Thus Fg compromises EC layer integrity causing downregulation and translocation of VE-cadherin and through MMP-9 activation. These results suggest that increased level of Fg could play a significant role in vascular dysfunction and remodeling.     

Understanding the origins of time-dependent inhibition by polypeptide deformylase inhibitors

The continual bacterial adaptation to antibiotics creates an ongoing medical need for the development of novel therapeutics. Polypeptide deformylase (PDF) is a highly conserved bacterial enzyme, which is essential for viability. It has previously been shown that PDF inhibitors represent a promising new area for the development of antimicrobial agents, and that many of the best PDF inhibitors demonstrate slow, time-dependent binding. To improve our understanding of the mechanistic origin of this time-dependent inhibition, we examined in detail the kinetics of PDF catalysis and inhibition by several different PDF inhibitors. Varying pH and solvent isotope led to clear changes in time-dependent inhibition parameters, as did inclusion of NaCl, which binds to the active site metal of PDF. Quantitative analysis of these results demonstrated that the observed time dependence arises from slow binding of the inhibitors to the active site metal. However, we also found several metal binding inhibitors that exhibited rapid, non-time-dependent onset of inhibition. By a combination of structural and chemical modification studies, we show that metal binding is only slow when the rest of the inhibitor makes optimal hydrogen bonds within the subsites of PDF. Both of these interactions between the inhibitor and enzyme were found to be necessary to observe time-dependent inhibition, as elimination of either leads to its loss.     

Time trends in testicular cancer in Croatia 1983-2007: rapid increases in incidence, no declines in mortality

Testicular cancer, although a rare malignancy, represents the most common cancer in young male populations of Western origin. While increasing incidence trends of testicular cancer have been reported, mortality is declining in many high-resource settings. Using national data from the Croatian National Cancer Registry for the period 1983-2007, time trends were analysed by joinpoint regression and Age-Period-Cohort models. The present study is the first to analyse the testicular cancer trends in the Croatian population. Over the 25-year period, a mean number of 89 incident cases and 13 deaths were reported annually. The observed mean annual increases in age-standardised rates were 7.0% for incidence and 1.6% for mortality, with no abrupt linear changes (joinpoints) identified. The incidence rates of testicular cancer incidence have been steeply increasing in successive cohorts born since the mid-1930s. The rapid rise in testicular cancer incidence in the Croatian population appears to be one of the highest rates of increase recorded in Europe and worldwide. The lack of decline in the mortality rates over time, while based on relatively few deaths, highlights a need for improvements in diagnostics and management of therapy in Croatia in order to improve the survival and quality-of-life of testicular cancer patients.     

Acylprolinamides: a new class of peptide deformylase inhibitors with in vivo antibacterial activity

A new class of PDF inhibitor with potent, broad spectrum antibacterial activity is described. Optimization of blood stability and potency provided compounds with improved pharmacokinetics that were suitable for in vivo experiments. Compound 5c, which has robust antibacterial activity, demonstrated efficacy in two respiratory tract infection models.     

Establishment of tree seedlings in the understory of restoration plantations: natural regeneration and enrichment plantings

Little is known about the potential of restoration plantations to provide appropriate understory conditions to support the establishment of seeds arriving from neighboring native forests. In this article, we investigated how seedling establishment is affected in the understory of restoration sites of different ages and assessed some of the potential environmental factors controlling this ecological process. We first compared the density and richness of native tree seedlings among 10‐, 22‐, and 55‐year‐old restoration plantations within the Atlantic Forest region of southeastern Brazil. Then, we undertook a seed addition experiment in each study site, during the wet season, and compared seedling emergence, survival, and biomass on local versus old‐growth forest soil (transferred from a reference ecosystem), in order to test whether local substrate could hamper seedling establishment. As expected, the oldest restoration site had higher density and richness of spontaneously regenerating seedlings. However, seedling establishment was less successful both in the oldest restoration planting and using substrate transferred from a reference ecosystem, where emergence and survival were lower, but surviving seedlings grew better. We attribute these results to lower light availability for seedlings in the understory of the oldest site and speculate that higher incidence of pathogens on old‐growth forest soil may have increased seedling mortality. We conclude that the understory of young restoration plantations provides suitable microsite conditions at the early establishment phases for the spontaneous regeneration or enrichment planting of native trees.     

Population Size Estimation of Men Who Have Sex with Men in Tbilisi,Georgia; Multiple Methods and Triangulation of Findings

Introduction

An accurate estimation of the population size of men who have sex with men (MSM) is critical to the success of HIV program planning and to monitoring of the response to epidemic as a whole, but is quite often missing. In this study, our aim was to estimate the population size of MSM in Tbilisi, Georgia and compare it with other estimates in the region.

Methods

In the absence of a gold standard for estimating the population size of MSM, this study reports a range of methods, including network scale-up, mobile/web apps multiplier, service and unique object multiplier, network-based capture-recapture, Handcock RDS-based and Wisdom of Crowds methods. To apply all these methods, two surveys were conducted: first, a household survey among 1,015 adults from the general population, and second, a respondent driven sample of 210 MSM. We also conducted a literature review of MSM size estimation in Eastern European and Central Asian countries.

Results

The median population size of MSM generated from all previously mentioned methods was estimated to be 5,100 (95% Confidence Interval (CI): 3,243 ~ 9,088). This corresponds to 1.42% (95%CI: 0.9% ~ 2.53%) of the adult male population in Tbilisi.

Conclusion

Our size estimates of the MSM population (1.42% (95%CI: 0.9% ~ 2.53%) of the adult male population in Tbilisi) fall within ranges reported in other Eastern European and Central Asian countries. These estimates can provide valuable information for country level HIV prevention program planning and evaluation. Furthermore, we believe, that our results will narrow the gap in data availability on the estimates of the population size of MSM in the region.     

A DFT investigation of a bulky biomimetic model catalyzing the 5′-outer ring deiodination of thyroxine

This paper illustrates the outcomes of a density functional theory investigation aimed at unraveling mechanistic aspects of the 5′-outer ring deiodination process of thyroxine (T4) assisted by the sterically protected organoselenol compound BpqSeH. BpqSeH, which was previously synthesized and tested for its deiodinase activity, is able to afford the active hormone 3,5,3′-tetraiodothyronine (T3) by selective outer-ring deiodination of T4, and to protect the SeH moiety inside the nano-sized molecular cavity from further reactivity, allowing its isolation and characterization. Calculations were also performed including an imidazole ring that, mimicking a His residue in the active site of the original enzyme, plays an crucial role in deprotonating the selenol moiety. Both the suggested enol/keto tautomerization and the previously proven formation of an intermediate whose main characteristic is the presence of a Se?I?C halogen bond, were examined along the pathway leading to 5′-outer ring deiodination. The calculated potential energy surface showed that neither the pathway encompassing enol/keto tautomerism nor the formation of a halogen bond paving the way to C–I bond breaking and chalcogen-I bond forming is viable. The exergonic formation of the final selenenyl iodide product confirms the stabilization effect of the molecular cavity.

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Graphical Abstract Computed free energy profile describing the 5′-outer deiodination of thyroxine assisted by the steric hindered organoselenol BpqSH compound. The molecular electrostatic potential map reoported for the INT1 intermediate shows the non-covalent Se-I interaction, due to the attraction between charges of opposite sign, that weakens the C-I bond and prepares the formation of the new Se-I bond.

     

Comparison of commercial and in-house Real-time PCR assays for quantification of Epstein-Barr virus (EBV) DNA in plasma

Background  

Epstein-Barr virus (EBV) DNA load monitoring is known to be useful for the diagnosis and monitoring of EBV-associated diseases. The aim of this study is to compare the performance of two real-time PCR assays for EBV DNA: a commercial kit as the Q-EBV Real-Time System (Q-EBV PCR, Amplimedical, Turin, Italy) and an in-house assay (EBV RQ-PCR).