Carotid plaque age is a feature of plaque stability inversely related to levels of plasma insulin

Background

The stability of atherosclerotic plaques determines the risk for rupture, which may lead to thrombus formation and potentially severe clinical complications such as myocardial infarction and stroke. Although the rate of plaque formation may be important for plaque stability, this process is not well understood. We took advantage of the atmospheric ¹⁴C-declination curve (a result of the atomic bomb tests in the 1950s and 1960s) to determine the average biological age of carotid plaques.

Methodology/Principal Finding

The cores of carotid plaques were dissected from 29 well-characterized, symptomatic patients with carotid stenosis and analyzed for ¹⁴C content by accelerator mass spectrometry. The average plaque age (i.e. formation time) was 9.6±3.3 years. All but two plaques had formed within 5–15 years before surgery. Plaque age was not associated with the chronological ages of the patients but was inversely related to plasma insulin levels (p = 0.0014). Most plaques were echo-lucent rather than echo-rich (2.24±0.97, range 1–5). However, plaques in the lowest tercile of plaque age (most recently formed) were characterized by further instability with a higher content of lipids and macrophages (67.8±12.4 vs. 50.4±6.2, p = 0.00005; 57.6±26.1 vs. 39.8±25.7, p<0.0005, respectively), less collagen (45.3±6.1 vs. 51.1±9.8, p<0.05), and fewer smooth muscle cells (130±31 vs. 141±21, p<0.05) than plaques in the highest tercile. Microarray analysis of plaques in the lowest tercile also showed increased activity of genes involved in immune responses and oxidative phosphorylation.

Conclusions/Significance

Our results show, for the first time, that plaque age, as judge by relative incorporation of ¹⁴C, can improve our understanding of carotid plaque stability and therefore risk for clinical complications. Our results also suggest that levels of plasma insulin might be involved in determining carotid plaque age.     

4-O-α-d-galactopyranosyl-d-galactose: Efficient synthetic routes from “polygalacturonic acid”

Enzymic hydrolysis of “polygalacturonic acid” gave a mixture of oligomers which was fractionated by ion-exchange chromatography. The resulting di- and tri-saccharides were treated, respectively, with methanol and ethylene oxide, and the resulting esters were reduced with sodium borohydride. Treatment of the products with acetic anhydride and sulfuric acid, followed by deacetylation, produced the title compound.     

Density functional theory study of structural and electronic properties of trans and cis structures of thiothixene as a nano-drug

The geometrical structure, electronic and optical properties, electronic absorption spectra, vibrational frequencies, natural charge distribution, MEP analysis and thermodynamic properties of the trans and cis structures of the drug thiothixene were investigated using density functional theory (DFT) and time-dependent DFT (TDDFT) methods with the B3LYP hybrid functional and 6–311?+?G(d,p) basis set. The results of the calculations demonstrate that the cis structure of thiothixene has appropriate quantum properties that can act as an active medicine. The relative energies of trans and cis structures of thiothixene shows that the cis structure is more stable than the trans structure, with a small energy difference. TDDFT calculations show that the cis structure of thiothixene has the best absorption properties. The calculated NLO properties show that the NLO properties of the cis structure of thiothixene are higher than the trans structure, and the fact that the chemical hardness of the cis structure is lower than that of the trans structure that indicates that the reactivity and charge transfer of the cis isomer of thiothixene is higher than that of trans thiothixene. The molecular electrostatic potential (MEP) maps of both structures of thiothixene demonstrate that the oxygen atoms of the molecule are appropriate areas for electrophilic reactions. The vibrational frequencies of the two conformations of thiothixene demonstrate that both structures of thiothixene have almost similar modes of vibrations. The calculated thermodynamic parameters show that these quantities increase with enhancing temperature due to the enhancement of molecular vibrational intensities with temperature.

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Graphical abstract Trans/Cis isomerization of thiothixene drug

     

New developments in ancient genomics

Ancient DNA research is on the crest of a 'third wave' of progress due to the introduction of a new generation of DNA sequencing technologies. Here we review the advantages and disadvantages of the four new DNA sequencers that are becoming available to researchers. These machines now allow the recovery of orders of magnitude more DNA sequence data, albeit as short sequence reads. Hence, the potential reassembly of complete ancient genomes seems imminent, and when used to screen libraries of ancient sequences, these methods are cost effective. This new wealth of data is also likely to herald investigations into the functional properties of extinct genes and gene complexes and will improve our understanding of the biological basis of extinct phenotypes.     

Ultrasonic monitoring of early-stage biofilm growth on polymeric surfaces

Biofilm growth on polymeric surfaces was monitored using ultrasonic frequency-domain reflectometry (UFDR). The materials utilized for this study included nonporous polycarbonate (PC) sheets, polyamide (PA) nanofiltration composite membranes and porous polyvinylidene fluoride (PVDF) microfiltration membranes (nominal pore size: 0.65 microm). Coupons of each material were placed in a biologically active annular reactor for up to 300 days, and subjected to a constant shear field (0.12 N m(-2)), which induced sessile microbial growth from acetate amended municipal tap water. Acoustic monitoring was non-destructively executed by traversing coupons in a constant temperature water bath using a spherically focused 20-MHz immersion transducer. This semi-automated system was configured to obtain reflections from 50 regions (c.a. 120x10(3) microm2) distributed evenly near the centerline of each coupon. The resulting reflected power distributions were compared with standard biochemical and microscopic assays that described surface associated biofilms. When compared to clean (virgin) conditions, biofilms growing on coupons induced consistent attenuations in reflection amplitude, which caused statistically significant shifts in reflected power (p<0.01). Using exocellular polysaccharides as a surrogate measure of total biofilm mass, UFDR was able to detect biofilms developing on any of the materials tested at surface-averaged masses < or = 150 microg cm(-2). Above these threshold levels, increasing amounts of exocellular polysaccharides correlated with significant decreases in total reflected power (TRP). The distribution of biomass on the coupon surfaces determined by acoustic spectra was consistent with that observed using environmental scanning electron microscopy (ESEM). These results suggest that UFDR may be used as a non-destructive tool to monitor biofouling in a wide variety of applications.     

A Sunken Ship of the Desert at the River Danube in Tulln,Austria

Rescue excavations recovered a skeleton that resurrect the contemporary dramatic history of Austria in the 17^th century as troops besieged Vienna in the second Osmanic-Habsburg war. Unique for Central Europe is the evidence of a completely preserved camel skeleton uncovered in a large refuse pit. The male individual of slender stature indicates a few but characteristic pathological changes revealing not a beast of burden but probably a valuable riding animal. Anatomical and morphometrical analyses suggest a hybrid confirmed by the ancient DNA analyses resulting in the presence of a dromedary in the maternal and a Bactrian camel in the paternal line.     

Microbial trans‐glutaminase enhances the physical and mechanical properties of depigmented wool

This study investigates the effects of enzymatic treatment with microbial trans‐glutaminase (m‐TGase) on the physical and mechanical properties of the depigmented wool yarns. Coarse pigmented wool yarns were treated with iron (II) followed by depigmentation with both oxidative and oxidative‐reductive chemicals. The depigmented wool yarns were then treated with m‐TGase to reduce the negative effects of the harsh chemicals. Diverse features of the wool yarns, including: tensile strength, elongation, color, diameter, moisture content, alkali solubility, and weight reduction, were measured before and after bleaching and enzymatic treatments. The treatment with the oxidative and reductive agents led to reduced tensile strength and elongation, and increased lightness, alkali solubility, and moisture content of the yarns. In contrast, the enzymatic treatment by m‐TGases cross‐linked the proteins of wool fibers via reaction between glutamine and lysine isodipeptide remediated the wool yarns. This improved the tensile strength and elongation and decreased the alkali solubility and moisture content. Fourier transform infrared spectroscopy (FTIR) was used to follow the chemical changes in wool fibres during depigmentation and enzymatic treatments.     

Therapeutic Effect of Transplanted Human Wharton’s Jelly Stem Cell-Derived Oligodendrocyte Progenitor Cells (hWJ-MSC-derived OPCs) in an Animal Model of Multiple Sclerosis

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS). A potential new therapeutic approach for MS is cell transplantation which may promote remyelination. We transplanted human Wharton’s jelly stem cell-derived oligodendrocyte progenitor cells (hWJ-MSC-derived OPCs) into the brain ventricles of mice induced with experimental autoimmune encephalomyelitis (EAE), the animal model of MS. We studied the effect of the transplanted OPCs on the functional and pathological manifestations of the disease. Transplanted hWJ-MSC-derived OPCs significantly reduced the clinical signs of EAE. Histological examinations showed that remyelination was significantly increased after transplantation. These results suggest that hWJ-MSC-derived OPCs promote the regeneration of myelin sheaths in the brain.     

Diet and cancer prevention: Dietary compounds,dietary MicroRNAs,and dietary exosomes

Cancer is one of main health public problems worldwide. Several factors are involved in beginning and development of cancer. Genetic and internal/external environmental factors can be as important agents that effect on emerging and development of several cancers. Diet and nutrition may be as one of important factors in prevention or treatment of various cancers. A large number studies indicated that suitable dietary patterns may help to cancer prevention or could inhibit development of tumor in cancer patients. Moreover, a large numbers studies indicated that a variety of dietary compounds such as curcumin, green tea, folat, selenium, and soy isoflavones show a wide range anti‐cancer properties. It has been showed that these compounds via targeting a sequence of cellular and molecular pathways could be used as suitable options for cancer chemoprevention and cancer therapy. Recently, dietary microRNAs and exosomes have been emerged as attractive players in cancer prevention and cancer therapy. These molecules could change behavior of cancer cells via targeting various cellular and molecular pathways involved in cancer pathogenesis. Hence, the utilization of dietary compounds which are associated with powerful molecules such as microRNAs and exosomes and put them in dietary patterns could contribute to prevention or treatment of various cancers. Here, we summarized various studies that assessed effect of dietary patterns on cancer prevention shortly. Moreover, we highlighted the utilization of dietary compounds, dietary microRNAs, and dietary exosomes and their cellular and molecular pathways in cancer chemoprevention.     

Conformational Flexibility Determines Selectivity and Antibacterial, Antiplasmodial, and Anticancer Potency of Cationic ��-Helical Peptides

We used a combination of fluorescence, circular dichroism (CD), and NMR spectroscopies in conjunction with size exclusion chromatography to help rationalize the relative antibacterial, antiplasmodial, and cytotoxic activities of a series of proline-free and proline-containing model antimicrobial peptides (AMPs) in terms of their structural properties. When compared with proline-free analogs, proline-containing peptides had greater activity against Gram-negative bacteria, two mammalian cancer cell lines, and intraerythrocytic Plasmodium falciparum, which they were capable of killing without causing hemolysis. In contrast, incorporation of proline did not have a consistent effect on peptide activity against Mycobacterium tuberculosis. In membrane-mimicking environments, structures with high α-helix content were adopted by both proline-free and proline-containing peptides. In solution, AMPs generally adopted disordered structures unless their sequences comprised more hydrophobic amino acids or until coordinating phosphate ions were added. Proline-containing peptides resisted ordering induced by either method. The roles of the angle subtended by positively charged amino acids and the positioning of the proline residues were also investigated. Careful positioning of proline residues in AMP sequences is required to enable the peptide to resist ordering and maintain optimal antibacterial activity, whereas varying the angle subtended by positively charged amino acids can attenuate hemolytic potential albeit with a modest reduction in potency. Maintaining conformational flexibility improves AMP potency and selectivity toward bacterial, plasmodial, and cancerous cells while enabling the targeting of intracellular pathogens.