Impact of advanced glycation end products (AGEs) signaling in coronary artery disease

Coronary artery disease remains the leading cause of mortality in adult diabetic population with however, a high predominance also in non-diabetic subjects. In search of common molecular mechanisms and metabolic by-products with potential pathogenic role, increased advanced glycation end products (AGEs) present a critical biomarker for CAD development in both cases. Interaction of AGEs with their transmembrane cell receptor, RAGE in endothelial and smooth muscle cells as well as in platelets, activates intracellular signaling that leads to endothelial injury, modulation of vascular smooth muscle cell function and altered platelet activity. Furthermore, tissue accumulation of AGEs affects current treatment approaches being involved in stent restenosis. The present review provides an update of AGE-induced molecular mechanisms involved in CAD pathophysiology while it discusses emerging therapeutic interventions targeting AGE reduction and AGE-RAGE signaling with beneficial clinical outcome.     

Laboratory Investigation and Phylogenetic Analysis of an Imported Middle East Respiratory Syndrome Coronavirus Case in Greece

Rapid and reliable laboratory diagnosis of persons suspected of Middle East respiratory syndrome coronavirus (MERS-CoV) infection is important for timely implementation of infection control practices and disease management. In addition, monitoring molecular changes in the virus can help elucidate chains of transmission and identify mutations that might influence virus transmission efficiency. This was illustrated by a recent laboratory investigation we conducted on an imported MERS-CoV case in Greece. Two oropharyngeal swab specimens were collected on the 1^st and 2^nd day of patient hospitalization and tested using two real-time RT-PCR (rRT-PCR) assays targeting the UpE and Orf-1a regions of the MERS-CoV genome and RT-PCR and partial sequencing of RNA-dependent RNA polymerase and nucleocapsid genes. Serum specimens were also collected and serological test were performed. Results from the first swab sample were inconclusive while the second swab was strongly positive for MERS-CoV RNA by rRT-PCR and confirmed positive by RT-PCR and partial gene sequencing. Positive serologic test results further confirmed MERS-CoV infection. Full-length nucleocapsid and spike gene coding sequences were later obtained from the positive swab sample. Phylogenetic analysis revealed that the virus was closely related to recent human-derived MERS-CoV strains obtained in Jeddah and Makkah, Saudi Arabia, in April 2014 and dromedary camels in Saudi Arabia and Qatar. These findings were consistent with the patient’s history. We also identified a unique amino acid substitution in the spike receptor binding domain that may have implications for receptor binding efficiency. Our initial inconclusive rRT-PCR results highlight the importance of collecting multiple specimens from suspect MERS-CoV cases and particularly specimens from the lower respiratory tract.     

Interannual Changes in Biomass Affect the Spatial Aggregations of Anchovy and Sardine as Evidenced by Geostatistical and Spatial Indicators

Geostatistical techniques were applied and a series of spatial indicators were calculated (occupation, aggregation, location, dispersion, spatial autocorrelation and overlap) to characterize the spatial distributions of European anchovy and sardine during summer. Two ecosystems were compared for this purpose, both located in the Mediterranean Sea: the Strait of Sicily (upwelling area) and the North Aegean Sea (continental shelf area, influenced by freshwater). Although the biomass of anchovy and sardine presented high interannual variability in both areas, the location of the centres of gravity and the main spatial patches of their populations were very similar between years. The size of the patches representing the dominant part of the abundance (80%) was mostly ecosystem- and species-specific. Occupation (area of presence) appears to be shaped by the extent of suitable habitats in each ecosystem whereas aggregation patterns (how the populations are distributed within the area of presence) were species-specific and related to levels of population biomass. In the upwelling area, both species showed consistently higher occupation values compared to the continental shelf area. Certain characteristics of the spatial distribution of sardine (e.g. spreading area, overlapping with anchovy) differed substantially between the two ecosystems. Principal component analysis of geostatistical and spatial indicators revealed that biomass was significantly related to a suite of, rather than single, spatial indicators. At the spatial scale of our study, strong correlations emerged between biomass and the first principal component axis with highly positive loadings for occupation, aggregation and patchiness, independently of species and ecosystem. Overlapping between anchovy and sardine increased with the increase of sardine biomass but decreased with the increase of anchovy. This contrasting pattern was attributed to the location of the respective major patches combined with the specific occupation patterns of the two species. The potential use of spatial indices as auxiliary stock monitoring indicators is discussed.     

A Customized Light Sheet Microscope to Measure Spatio-Temporal Protein Dynamics in Small Model Organisms

We describe a customizable and cost-effective light sheet microscopy (LSM) platform for rapid three-dimensional imaging of protein dynamics in small model organisms. The system is designed for high acquisition speeds and enables extended time-lapse in vivo experiments when using fluorescently labeled specimens. We demonstrate the capability of the setup to monitor gene expression and protein localization during ageing and upon starvation stress in longitudinal studies in individual or small groups of adult Caenorhabditis elegans nematodes. The system is equipped to readily perform fluorescence recovery after photobleaching (FRAP), which allows monitoring protein recovery and distribution under low photobleaching conditions. Our imaging platform is designed to easily switch between light sheet microscopy and optical projection tomography (OPT) modalities. The setup permits monitoring of spatio-temporal expression and localization of ageing biomarkers of subcellular size and can be conveniently adapted to image a wide range of small model organisms and tissue samples.     

Towards a mechanistic understanding of reciprocal drug–microbiome interactions

Broad‐spectrum antibiotics target multiple gram‐positive and gram‐negative bacteria, and can collaterally damage the gut microbiota. Yet, our knowledge of the extent of damage, the antibiotic activity spectra, and the resistance mechanisms of gut microbes is sparse. This limits our ability to mitigate microbiome‐facilitated spread of antibiotic resistance. In addition to antibiotics, non‐antibiotic drugs affect the human microbiome, as shown by metagenomics as well as in vitro studies. Microbiome–drug interactions are bidirectional, as microbes can also modulate drugs. Chemical modifications of antibiotics mostly function as antimicrobial resistance mechanisms, while metabolism of non‐antibiotics can also change the drugs’ pharmacodynamic, pharmacokinetic, and toxic properties. Recent studies have started to unravel the extensive capacity of gut microbes to metabolize drugs, the mechanisms, and the relevance of such events for drug treatment. These findings raise the question whether and to which degree these reciprocal drug–microbiome interactions will differ across individuals, and how to take them into account in drug discovery and precision medicine. This review describes recent developments in the field and discusses future study areas that will benefit from systems biology approaches to better understand the mechanistic role of the human gut microbiota in drug actions.     

Effects of two different half-squat training programs on fatigue during repeated cycling sprints in soccer players

This study compared the effects of two different half-squat training programs on the repeated-sprint ability of soccer players during the preseason. Twenty male professional soccer players were divided into 2 groups: One group (S-group) performed 4 sets of 5 repetitions with 90% of their 1-repetition maximum (1RM), and the other group (H-group) performed 4 sets of 12 repetitions with 70% of 1RM, 3 times per week for 6 weeks, in addition to their common preseason training program. Repeated-sprint ability was assessed before and after training by 10 × 6-second cycle ergometer sprints separated by 24 seconds of passive recovery. Maximal half-squat strength increased significantly in both groups (p < 0.01), but this increase was significantly greater in the S-group compared with the H-group (17.3 ± 1.9 vs. 11.0 ± 1.9%, p < 0.05). Lean leg volume (LLV) increased only in the H-group. Total work over the 10 sprints improved in both groups after training, but this increase was significantly greater in the second half (8.9 ± 2.6%) compared with the first half of the sprint test (3.2 ± 1.7%) only in the S-group. Mean power output (MPO) expressed per liter of LLV was better maintained during the last 6 sprints posttraining only in the S-group, whereas there was no change in MPO per LLV in the H-group over the 10 sprints. These results suggest that resistance training with high loads is superior to a moderate-load program, because it increases strength without a change in muscle mass and also results in a greater improvement in repeated sprint ability. Therefore, resistance training with high loads may be preferable when the aim is to improve maximal strength and fatigue during sprinting in professional soccer players.