Cannabigerol: a bibliometric overview and review of research on an important phytocannabinoid

Phytochemistry Reviews - Cannabigerol (CBG) is one of the major phytocannabinoids present in Cannabis sativa L. but is presumed to be an artefact or degradation product of cannabigerolic acid...     

Teleosts as models for human vertebral stability and deformity

Vertebral development is a dynamic and complicated process, and defects can be caused by a variety of influences. Spinal curvature with no known cause (idiopathic scoliosis) affects 2-3% of the human population. In order to understand the etiology and pathogenesis of complex human skeletal defects such as idiopathic scoliosis, multiple models must be used to study all of the factors affecting vertebral stability and deformity. Although fish and humans have many of the same types of offenses to vertebral integrity, they have been overlooked as a resource for study. The most common morphological deformity reported for fish are those that occur during the development of the spinal system, and as with humans, curvature is a common morphological consequence. Here we review spinal curvature in teleosts and suggest that they are an unexploited resource for understanding the basic elements of vertebral stability, deformity, development and genetics. Fish can be a value to vertebral research because they are tractable, have a diversity of non-induced vertebral deformities, and substantial genomic resources. Current animal models lack non-induced deformities and the experimental tractability necessary for genetic studies. The fact that fish are free of an appendicular skeleton should allow for analysis of basic spinal integrity without the biomechanical constraints observed in quadrupedal and bipedal models. To illustrate the point we review human idiopathic scoliosis and the potential contribution teleosts can make for the identification of causes, risk factors, and treatment options.     

Organellar proteomics of human platelet dense granules reveals that 14-3-3zeta is a granule protein related to atherosclerosis

Dense granules, a type of platelet secretory organelle, are known to accumulate high concentrations of small molecules such as calcium, adenine nucleotides, serotonin, pyrophosphate, and polyphosphate. Protein composition of these granules has been obscure, however. In this paper, we use proteomics techniques to describe, for the first time, the soluble protein composition of platelet dense granules. We have isolated highly enriched human platelet dense granule fractions that have been analyzed using two proteomics methods. Using this approach, we have identified 40 proteins, and most of them, such as actin-associated proteins, glycolytic enzymes, and regulatory proteins, have not previously been related to the organelle. We have focused our efforts on studying 14-3-3zeta, a member of a conserved family of proteins that interact with hundreds of different proteins. We have demonstrated that 14-3-3zeta is localized mostly on dense granules and that it is secreted after platelet activation. As some proteins secreted from activated platelets could promote the development of atherosclerosis and thrombosis, we have studied the expression of 14-3-3zeta in sections of human abdominal aorta of patients with aneurysm, identifying it at the atherosclerotic plaques. Together, our results reveal new details of the composition of the platelet dense granule and suggest an extracellular function for 14-3-3zeta associated with atherosclerosis.     

Spontaneous altruism by chimpanzees and young children

People often act on behalf of others. They do so without immediate personal gain, at cost to themselves, and even toward unfamiliar individuals. Many researchers have claimed that such altruism emanates from a species-unique psychology not found in humans' closest living evolutionary relatives, such as the chimpanzee. In favor of this view, the few experimental studies on altruism in chimpanzees have produced mostly negative results. In contrast, we report experimental evidence that chimpanzees perform basic forms of helping in the absence of rewards spontaneously and repeatedly toward humans and conspecifics. In two comparative studies, semi–free ranging chimpanzees helped an unfamiliar human to the same degree as did human infants, irrespective of being rewarded (experiment 1) or whether the helping was costly (experiment 2). In a third study, chimpanzees helped an unrelated conspecific gain access to food in a novel situation that required subjects to use a newly acquired skill on behalf of another individual. These results indicate that chimpanzees share crucial aspects of altruism with humans, suggesting that the roots of human altruism may go deeper than previous experimental evidence suggested.     

Computational approach for identification and characterization of GPI-anchored peptides in proteomics experiments

Genes that encode glycosylphosphatidylinositol anchored proteins (GPI-APs) constitute an estimated 1-2% of eukaryote genomes. Current computational methods for the prediction of GPI-APs are sensitive and specific; however, the analysis of the processing site (omega- or omega-site) of GPI-APs is still challenging. Only 10% of the proteins that are annotated as GPI-APs have the omega-site experimentally verified. We describe an integrated computational and experimental proteomics approach for the identification and characterization of GPI-APs that provides the means to identify GPI-APs and the derived GPI-anchored peptides in LC-MS/MS data sets. The method takes advantage of sequence features of GPI-APs and the known core structure of the GPI-anchor. The first stage of the analysis encompasses LC-MS/MS based protein identification. The second stage involves prediction of the processing sites of the identified GPI-APs and prediction of the corresponding terminal tryptic peptides. The third stage calculates possible GPI structures on the peptides from stage two. The fourth stage calculates the scores by comparing the theoretical spectra of the predicted GPI-peptides against the observed MS/MS spectra. Automated identification of C-terminal GPI-peptides from porcine membrane dipeptidase, folate receptor and CD59 in complex LC-MS/MS data sets demonstrates the sensitivity and specificity of this integrated computational and experimental approach.     

Multiple-contrast X-ray micro-CT visualization of colon malformations and tumours in situ in living mice

The development of new therapeutic approaches against colorectal cancer requires preclinical studies in mice. In vivo imaging could greatly facilitate these trials, but the small size of the animals is a major limitation for the direct visualization of intestinal tissue. Here we report a method of in vivo imaging of the mouse intestine based on X-ray micro-computed tomography using multiple contrast agents. This method was validated in the model of non-cancerous polyp-like heteroplasia that spontaneously develops in the caecum area of Cdx2+/- mutant mice and in the model of colon adenocarcinoma induced by administration of the chemical carcinogen azoxymethane. As a simple and non-invasive method, multiple-contrast X-ray micro-computed tomography is appropriate for pre-clinical studies of intestinal diseases in living mice.     

Immune activation suppresses initiation of lytic Epstein-Barr virus infection

Primary infection with Epstein-Barr virus (EBV) is asymptomatic in children with immature immune systems but may manifest as infectious mononucleosis, a vigorous immune activation, in adolescents or adults with mature immune systems. Infectious mononucleosis and chronic immune activation are linked to increased risk for EBV-associated lymphoma. Here we show that EBV initiates progressive lytic infection by expression of BZLF-1 and the late lytic genes gp85 and gp350/220 in cord blood mononuclear cells (CBMC) but not in peripheral blood mononuclear cells (PBMC) from EBV-naive adults after EBV infection ex vivo. Lower levels of proinflammatory cytokines in CBMC, used to model a state of minimal immune activation and immature immunity, than in PBMC were associated with lytic EBV infection. Triggering the innate immunity specifically via Toll-like receptor-9 of B cells substantially suppressed BZLF-1 mRNA expression in acute EBV infection ex vivo and in anti-IgG-stimulated chronically latently EBV-infected Akata Burkitt lymphoma cells. This was mediated in part by IL-12 and IFN-gamma. These results identify immune activation as critical factor for the suppression of initiation of lytic EBV infection. We hypothesize that immune activation contributes to EBV-associated lymphomagenesis by suppressing lytic EBV and in turn promotes latent EBV with transformation potential.     

Experimental Evolution of an RNA Virus in Wild Birds: Evidence for Host-Dependent Impacts on Population Structure and Competitive Fitness

Within hosts, RNA viruses form populations that are genetically and phenotypically complex. Heterogeneity in RNA virus genomes arises due to error-prone replication and is reduced by stochastic and selective mechanisms that are incompletely understood. Defining how natural selection shapes RNA virus populations is critical because it can inform treatment paradigms and enhance control efforts. We allowed West Nile virus (WNV) to replicate in wild-caught American crows, house sparrows and American robins to assess how natural selection shapes RNA virus populations in ecologically relevant hosts that differ in susceptibility to virus-induced mortality. After five sequential passages in each bird species, we examined the phenotype and population diversity of WNV through fitness competition assays and next generation sequencing. We demonstrate that fitness gains occur in a species-specific manner, with the greatest replicative fitness gains in robin-passaged WNV and the least in WNV passaged in crows. Sequencing data revealed that intrahost WNV populations were strongly influenced by purifying selection and the overall complexity of the viral populations was similar among passaged hosts. However, the selective pressures that control WNV populations seem to be bird species-dependent. Specifically, crow-passaged WNV populations contained the most unique mutations (~1.7× more than sparrows, ~3.4× more than robins) and defective genomes (~1.4× greater than sparrows, ~2.7× greater than robins), but the lowest average mutation frequency (about equal to sparrows, ~2.6× lower than robins). Therefore, our data suggest that WNV replication in the most disease-susceptible bird species is positively associated with virus mutational tolerance, likely via complementation, and negatively associated with the strength of selection. These differences in genetic composition most likely have distinct phenotypic consequences for the virus populations. Taken together, these results reveal important insights into how different hosts may contribute to the emergence of RNA viruses.     

Current status of clinically available bioresorbable scaffolds in percutaneous coronary interventions

Drug-eluting stents (DES) are widely used as first choice devices in percutaneous coronary interventions. However, certain concerns are associated with the use of DES, i.e. delayed arterial healing with a subsequent risk of neo-atherosclerosis, late stent thrombosis and hypersensitivity reactions to the DES polymer. Bioresorbable vascular scaffolds are the next step in percutaneous coronary interventions introducing the concept of supporting the natural healing process following initial intervention without leaving any foreign body materials resulting in late adverse events. The first-generation devices have shown encouraging results in multiple studies of selected patients up to the point of full bioresorption, supporting the introduction in regular patient care. During its introduction in daily clinical practice outside the previously selected patient groups, a careful approach should be followed in which outcome is continuously monitored.