Free cholesterol in atherosclerotic plaques: where does it come from?

PURPOSE OF REVIEW: Free cholesterol in plaques is an emerging contributing factor to lesion instability and, until recently, apoptosis of lipid-laden macrophages was considered the major source of free cholesterol. The validity of this concept is beginning to be challenged since there is recent evidence of erythrocyte membrane-derived cholesterol in plaques. Therefore, intraplaque hemorrhage may not be a passive event, as once considered as studies continue to support the relationship of intraplaque hemorrhage and necrotic core expansion. RECENT FINDINGS: The association of intraplaque hemorrhage, accumulated free cholesterol, and necrotic core expansion is beginning to unfold and recent MRI studies suggest the value of intraplaque hemorrhage as a predictor of recurrent cerebrovascular events. The amount of erythrocyte membrane-derived cholesterol is also suggested to be a measure of lesion vulnerability in acute coronary syndromes. Recent inhibitors studies of vascular permeability factors further emphasize the importance of intraplaque hemorrhage in plaque progression. Finally, DNA microarray analysis is starting to reveal key molecules involved in the accumulation of free cholesterol that are selectively induced in high-risk plaques. SUMMARY: These recent findings emphasize the importance of intraplaque hemorrhage as a contributor of free cholesterol in plaques and point to its provocative role in lesion destabilization.     

Pollen tube growth: where does the energy come from?

This review focuses on the energy metabolism during pollen maturation and tube growth and updates current knowledge. Pollen tube growth is essential for male reproductive success and extremely fast. Therefore, pollen development and tube growth are high energy-demanding processes. During the last years, various publications (including research papers and reviews) emphasize the importance of mitochondrial respiration and fermentation during male gametogenesis and pollen tube elongation. These pathways obviously contribute to satisfy the high energy demand, and there are many studies which suggest that respiration and fermentation are the only pathways to generate the needed energy. Here, we review data which show for the first time that in addition plastidial glycolysis and the balancing of the ATP/NAD(P)H ratio (by malate valves and NAD⁺ biosynthesis) contribute to satisfy the energy demand during pollen development. Although the importance of energy generation by plastids was discounted during the last years (possibly due to the controversial opinion about their existence in pollen grains and pollen tubes), the available data underline their prime role during pollen maturation and tube growth.     

Intra‐individual polymorphism in chloroplasts from NGS data: where does it come from and how to handle it?

Next‐generation sequencing allows access to a large quantity of genomic data. In plants, several studies used whole chloroplast genome sequences for inferring phylogeography or phylogeny. Even though the chloroplast is a haploid organelle, NGS plastome data identified a nonnegligible number of intra‐individual polymorphic SNPs. Such observations could have several causes such as sequencing errors, the presence of heteroplasmy or transfer of chloroplast sequences in the nuclear and mitochondrial genomes. The occurrence of allelic diversity has practical important impacts on the identification of diversity, the analysis of the chloroplast data and beyond that, significant evolutionary questions. In this study, we show that the observed intra‐individual polymorphism of chloroplast sequence data is probably the result of plastid DNA transferred into the mitochondrial and/or the nuclear genomes. We further assess nine different bioinformatics pipelines’ error rates for SNP and genotypes calling using SNPs identified in Sanger sequencing. Specific pipelines are adequate to deal with this issue, optimizing both specificity and sensitivity. Our results will allow a proper use of whole chloroplast NGS sequence and will allow a better handling of NGS chloroplast sequence diversity.     

The restoration of biodiversity: where has research been and where does it need to go?

The practice of ecological restoration is a primary option for increasing levels of biodiversity by modifying human-altered ecosystems. The scientific discipline of restoration ecology provides conceptual guidance and tests of restoration strategies, with the ultimate goal of predictive landscape restoration. I construct a conceptual model for restoration of biodiversity, based on site-level (e.g., biotic and abiotic) conditions, landscape (e.g, interpatch connectivity and patch geometry), and historical factors (e.g., species arrival order and land-use legacies). I then ask how well restoration ecology has addressed the various components of this model. During the past decade, restoration research has focused largely on how the restoration of site-level factors promotes species diversity-primarily of plants. Relatively little attention has been paid to how landscape or historical factors interplay with restoration, how restoration influences functional and genetic components of biodiversity, or how a suite of less-studied taxa might be restored. I suggest that the high level of variation seen in restoration outcomes might be explained, at least in part, by the contingencies placed on site-level restoration by landscape and historical factors and then present a number of avenues for future research to address these often ignored linkages in the biodiversity restoration model. Such work will require carefully conducted restoration experiments set across multiple sites and many years. It is my hope that by considering how space and time influence restoration, we might move restoration ecology in a direction of stronger prediction, conducted across landscapes, thus providing feasible restoration strategies that work at scales over which biodiversity conservation occurs.     

Alpha, beta, or gamma: where does all the diversity go?

Global taxonomic richness is affected by variation in three components: within-community, or alpha, diversity, between-community, or beta, diversity; and between-region, or gamma, diversity. A data set consisting of 505 faunal lists distributed among 40 stratigraphic intervals and six environmental zones was used to investigate how variation of alpha and beta diversity influenced global diversity through the Paleozoic, and especially during the Ordovician radiations. As first shown by Bambach (1977), alpha diversity increased by 50 to 70 percent in offshore marine environments during the Ordovician and then remained essentially constant of the remainder of the Paleozoic. The increase is insufficient, however, to account for the 300 percent rise observed in global generic diversity. It is shown that beta diversity among level, soft-bottom communities also increased significantly during the early Paleozoic. This change is related to enhanced habitat selection, and presumably increased overall specialization, among diversifying taxa during the Ordovician radiations. Combined with alpha diversity, the measured change in beta diversity still accounts for only about half of the increase in global diversity. Other sources of increase are probably not related to variation in gamma diversity but rather to appearance and/or expansion of organic reefs, hardground communities, bryozoan thickets, and crinoid gardens during the Ordovician.     

Treatment options in end-stage heart failure: where to go from here?

Chronic heart failure is a major healthcare problem associated with high morbidity and mortality. Despite significant progress in treatment strategies, the prognosis of heart failure patients remains poor. The golden standard treatment for heart failure is heart transplantation after failure of medical therapy, surgery and/or cardiac resynchronisation therapy. In order to improve patients' outcome and quality of life, new emerging treatment modalities are currently being investigated, including mechanical cardiac support devices, of which the left ventricular assist device is the most promising treatment option. Structured care for heart failure patients according to the most recent international heart failure guidelines may further contribute to optimal decision-making. This article will review the conventional and novel treatment modalities of heart failure.     

Research in the exercise sciences: where do we go from here?

The goal of this article is to provide a perspective on how research involving the acute and chronic effects of exercise (referred to as "exercise sciences") on the structure and function of organs systems will evolve in the next century. Within the last 30 years, exercise-related research has rapidly transitioned from an organ to a subcellular/molecular focus. Thus future research will continue to be heavily influenced by molecular biology tools, fueled by both emerging technologies (e.g., "gene-chip microarrays") designed to dissect gene function on a macro scale as well as by the completion of the human genome project in which the approximately 80,000 genes comprising humans will be completely sequenced. These successes will drive the emerging fields of functional genomics (the dissecting of a gene's identity and function) and proteomics (the study of the properties of proteins). Funding levels at the National Institutes of Health will likely increase in order to expand these emerging fields as well as provide avenues for translating fundamental knowledge into solving the complexities of a number of degenerative diseases influenced heavily by activity/inactivity factors such as cardiopulmonary disease, diabetes, obesity, and the debilitating disorders associated with aging. Thus there are many challenges facing future exercise scientists who must harness the new technologies and take an aggressive stance in bringing this important field to the forefront.     

Who is where in the Plastisphere,and why does it matter?

To fully understand how plastic is affecting the ocean, we need to understand how marine life interacts directly with it. Besides their ecological relevance, microbes can affect the distribution, degradation and transfer of plastics to the rest of the marine food web. From amplicon sequencing and scanning electron microscopy, we know that a diverse array of microorganisms rapidly associate with plastic marine debris in the form of biofouling and biofilms, also known as the “Plastisphere.” However, observation of multiple microbial interactions in situ, at small spatial scales in the Plastisphere, has been a challenge. In this issue of Molecular Ecology Resources, Schlundt et al. apply the combination labelling and spectral imaging – fluorescence in situ hybridization to study microbial communities on plastic marine debris. The images demonstrate the colocalization of abundant bacterial groups on plastic marine debris at a relatively high taxonomic and spatial resolution while also visualizing biofouling of eukaryotes, such as diatoms and bryozoans. This modern imaging technology provides new possibilities to address questions regarding the ecology of marine microbes on plastic marine debris and describe more specific impacts of plastic pollution in the marine food webs.     

Where do you come from,where do you go? Directional migration rates in landscape genetics

Identifying landscape elements that influence gene flow and migration in wild species is the current main topic of landscape genetics. Most landscape genetic studies infer gene flow and migration from genetic distances among populations or individuals and statistically relate these measurements to landscape composition and configuration. This approach assumes symmetrical gene flow between pairs of populations. Such an assumption, however, will often be violated, especially in source–sink systems. Source populations provide more emigrants than they receive immigrants, and sink populations get many immigrants, but release few emigrants. Source–sink dynamics cannot be explored using common landscape genetic approaches relying on genetic distances. In this issue of Molecular Ecology, Andreasen et al. ( 2012 ) apply an alternative approach allowing them to infer asymmetrical migration. They use a Bayesian assignment test among objectively defined populations of mountain lions (Puma concolor) in western USA to estimate recent and directional migration rates. The study shows that an area with a high amount of wildlife refuges and low hunting pressure harbours a source population for mountain lion dispersal, while areas with high hunting pressures form sink populations; a result helpful in making informed decisions in conservation management.     

Zebra mussels in Italy: where do they come from?

The zebra mussel Dreissena polymorpha is widely present in Italy, but Italian populations of this bivalve have never been genetically characterized. The mitochondrial Cytochrome Oxidase subunit I gene fragments have been used to determine the genetic structures of 3 populations from Lake Garda (n = 30), the first Italian basin colonized by this species, as well as 2 populations from Lake Constance, Germany (n = 14). A Neighbor-Joining tree and a Maximum Likelihood analysis were performed with 4 new Italian (LG1-LG4) and 3 German (LC1-LC3) haplotypes, also considering all the available Dreissena sequences from GenBank in order to estimate phylogeographic relationships. Almost all Italian haplotypes clustered with German and mid-European samples providing evidences of a mixed origin for Italian mussels. We speculate about Lake Garda colonization, for which the hypothesized "German origin" has been partially confirmed as well as the necessity of more efficient control strategies at least to minimize new colonizations.     

No Nogo: now where to go?

Nogo-A, a reticulon protein expressed by oligodendrocytes, contributes to the axonal growth inhibitory action of central myelin in growth cone collapse and neurite outgrowth in vitro assays, and antibody and inhibitor studies have implicated a role for Nogo in regeneration in the adult CNS in vivo. Three independent labs have now produced Nogo knockout mice with, quite unexpectedly, three different regeneration phenotypes.     

Sexual selection in hermaphrodites: where did our ideas come from?

Interpretations of hermaphroditism have been influenced by theold idea that organisms can be arranged in a series from lowerto higher, with human beings at the top, leading toward theangels and God (the scala naturae). The consequent notion thathermaphroditism is a primitive condition is still with us. Suchissues need to be addressed empirically, in a phylogenetic context.Darwin's theory of sexual selection provided the key to understandingsex switches, but it was not invoked until 1969 when it wasconjoined with ideas about relative size influenced by the workof Bernhard Rensch. In principle the problem could have beensolved a century earlier, and genetics was misleading ratherthan helpful. What really helped was an appreciation of Darwin'snonteleological way of thinking.     

Human infectious diseases in the genomics era: where do we go from here?

Ripudaman K Bains is the editor of the Genome Biology special issue content on the ‘genomics of infectious diseases’, and introduces the collection in this editorial.     

Glioma development: where did it all go wrong?

Investigating the family tree of a tumor to identify its cellular origins is a daunting task. Liu et al. (2011) now use an elegant lineage tracing technique (MADM) to visualize glioma from its earliest stages. They show that mutations originally induced in neural stem cells lie dormant and only trigger malignant transformation following differentiation into oligodendrocyte precursor cells.     

Synaptonemal complex formation: where does it start?

The synaptonemal complex is a prominent, evolutionarily conserved feature of meiotic prophase. The assembly of this structure is closely linked to meiotic recombination. A recent study in budding yeast reveals an unexpected role in centromere pairing for a protein component of the synaptonemal complex, Zip1. These findings have implications for synaptonemal complex formation.