Identification of hydroxyapatite spherules provides new insight into subretinal pigment epithelial deposit formation in the aging eye.

Accumulation of protein- and lipid-containing deposits external to the retinal pigment epithelium (RPE) is common in the aging eye, and has long been viewed as the hallmark of age-related macular degeneration (AMD). The cause for the accumulation and retention of molecules in the sub-RPE space, however, remains an enigma. Here, we present fluorescence microscopy and X-ray diffraction evidence for the formation of small (0.5-20 μm in diameter), hollow, hydroxyapatite (HAP) spherules in Bruch's membrane in human eyes. These spherules are distinct in form, placement, and staining from the well-known calcification of the elastin layer of the aging Bruch's membrane. Secondary ion mass spectrometry (SIMS) imaging confirmed the presence of calcium phosphate in the spherules and identified cholesterol enrichment in their core. Using HAP-selective fluorescent dyes, we show that all types of sub-RPE deposits in the macula, as well as in the periphery, contain numerous HAP spherules. Immunohistochemical labeling for proteins characteristic of sub-RPE deposits, such as complement factor H, vitronectin, and amyloid beta, revealed that HAP spherules were coated with these proteins. HAP spherules were also found outside the sub-RPE deposits, ready to bind proteins at the RPE/choroid interface. Based on these results, we propose a novel mechanism for the growth, and possibly even the formation, of sub-RPE deposits, namely, that the deposit growth and formation begin with the deposition of insoluble HAP shells around naturally occurring, cholesterol-containing extracellular lipid droplets at the RPE/choroid interface; proteins and lipids then attach to these shells, initiating or supporting the growth of sub-RPE deposits

Species-level functional profiling of metagenomes and metatranscriptomes.

Functional profiles of microbial communities are typically generated using comprehensive metagenomic or metatranscriptomic sequence read searches, which are time-consuming, prone to spurious mapping, and often limited to community-level quantification. We developed HUMAnN2, a tiered search strategy that enables fast, accurate, and species-resolved functional profiling of host-associated and environmental communities. HUMAnN2 identifies a community's known species, aligns reads to their pangenomes, performs translated search on unclassified reads, and finally quantifies gene families and pathways. Relative to pure translated search, HUMAnN2 is faster and produces more accurate gene family profiles. We applied HUMAnN2 to study clinal variation in marine metabolism, ecological contribution patterns among human microbiome pathways, variation in species' genomic versus transcriptional contributions, and strain profiling. Further, we introduce 'contributional diversity' to explain patterns of ecological assembly across different microbial community types

Biopsy confirmation of metastatic sites in breast cancer patients:clinical impact and future perspectives

Determination of hormone receptor (estrogen receptor and progesterone receptor) and human epidermal growth factor receptor 2 status in the primary tumor is clinically relevant to define breast cancer subtypes, clinical outcome,and the choice of therapy. Retrospective and prospective studies suggest that there is substantial discordance in receptor status between primary and recurrent breast cancer. Despite this evidence and current recommendations,the acquisition of tissue from metastatic deposits is not routine practice. As a consequence, therapeutic decisions for treatment in the metastatic setting are based on the features of the primary tumor. Reasons for this attitude include the invasiveness of the procedure and the unreliable outcome of biopsy, in particular for biopsies of lesions at complex visceral sites. Improvements in interventional radiology techniques mean that most metastatic sites are now accessible by minimally invasive methods, including surgery. In our opinion, since biopsies are diagnostic and changes in biological features between the primary and secondary tumors can occur, the routine biopsy of metastatic disease needs to be performed. In this review, we discuss the rationale for biopsy of suspected breast cancer metastases, review issues and caveats surrounding discordance of biomarker status between primary and metastatic tumors, and provide insights for deciding when to perform biopsy of suspected metastases and which one (s) to biopsy. We also speculate on the future translational implications for biopsy of suspected metastatic lesions in the context of clinical trials and the establishment of bio-banks of biopsy material taken from metastatic sites. We believe that such bio-banks will be important for exploring mechanisms of metastasis. In the future,advances in targeted therapy will depend on the availability of metastatic tissue

Development and formative evaluation of the e-Health implementation toolkit

<b>Background</b> The use of Information and Communication Technology (ICT) or e-Health is seen as essential for a modern, cost-effective health service. However, there are well documented problems with implementation of e-Health initiatives, despite the existence of a great deal of research into how best to implement e-Health (an example of the gap between research and practice). This paper reports on the development and formative evaluation of an e-Health Implementation Toolkit (e-HIT) which aims to summarise and synthesise new and existing research on implementation of e-Health initiatives, and present it to senior managers in a user-friendly format.<p></p> <b>Results</b> The content of the e-HIT was derived by combining data from a systematic review of reviews of barriers and facilitators to implementation of e-Health initiatives with qualitative data derived from interviews of "implementers", that is people who had been charged with implementing an e-Health initiative. These data were summarised, synthesised and combined with the constructs from the Normalisation Process Model. The software for the toolkit was developed by a commercial company (RocketScience). Formative evaluation was undertaken by obtaining user feedback. There are three components to the toolkit - a section on background and instructions for use aimed at novice users; the toolkit itself; and the report generated by completing the toolkit. It is available to download from http://www.ucl.ac.uk/pcph/research/ehealth/documents/e-HIT.xls<p></p> <b>Conclusions</b> The e-HIT shows potential as a tool for enhancing future e-Health implementations. Further work is needed to make it fully web-enabled, and to determine its predictive potential for future implementations

Atom--Molecule Coherence in a Bose-Einstein Condensate

Coherent coupling between atoms and molecules in a Bose-Einstein condensate (BEC) has been observed. Oscillations between atomic and molecular states were excited by sudden changes in the magnetic field near a Feshbach resonance and persisted for many periods of the oscillation. The oscillation frequency was measured over a large range of magnetic fields and is in excellent quantitative agreement with the energy difference between the colliding atom threshold energy and the energy of the bound molecular state. This agreement indicates that we have created a quantum superposition of atoms and diatomic molecules, which are chemically different species.Comment: 7 pages, 6 figure

Neo-Aristotelian Naturalism and the Evolutionary Objection: Rethinking the Relevance of Empirical Science

Neo-Aristotelian metaethical naturalism is a modern attempt at naturalizing ethics using ideas from Aristotle’s teleological metaphysics. Proponents of this view argue that moral virtue in human beings is an instance of natural goodness, a kind of goodness supposedly also found in the realm of non-human living things. Many critics question whether neo-Aristotelian naturalism is tenable in light of modern evolutionary biology. Two influential lines of objection have appealed to an evolutionary understanding of human nature and natural teleology to argue against this view. In this paper, I offer a reconstruction of these two seemingly different lines of objection as raising instances of the same dilemma, giving neo-Aristotelians a choice between contradicting our considered moral judgment and abandoning metaethical naturalism. I argue that resolving the dilemma requires showing a particular kind of continuity between the norms of moral virtue and norms that are necessary for understanding non-human living things. I also argue that in order to show such a continuity, neo-Aristotelians need to revise the relationship they adopt with empirical science and acknowledge that the latter is relevant to assessing their central commitments regarding living things. Finally, I argue that to move this debate forward, both neo-Aristotelians and their critics should pay attention to recent work on the concept of organism in evolutionary and developmental biology

State of the California current 2012-13: No such thing as an “average” year

This report reviews the state of the California Current System (CCS) between winter 2012 and spring 2013, and includes observations from Washington State to Baja California. During 2012, large-scale climate modes indicated the CCS remained in a cool, productive phase present since 2007. The upwelling season was delayed north of 42°N, but regions to the south, especially 33° to 36°N, experienced average to above average upwelling that persisted throughout the summer. Contrary to the indication of high production suggested by the climate indices, chlorophyll observed from surveys and remote sensing was below average along much of the coast. As well, some members of the forage assemblages along the coast experienced low abundances in 2012 surveys. Specifically, the concentrations of all lifestages observed directly or from egg densities of Pacific sardine, Sardinops sagax, and northern anchovy, Engraulis mordax, were less than previous years’ survey estimates. However, 2013 surveys and observations indicate an increase in abundance of northern anchovy. During winter 2011/2012, the increased presence of northern copepod species off northern California was consistent with stronger southward transport. Krill and small-fraction zooplankton abundances, where examined, were generally above average. North of 42°N, salps returned to typical abundances in 2012 after greater observed concentrations in 2010 and 2011. In contrast, salp abundance off central and southern California increased after a period of southward transport during winter 2011/2012. Reproductive success of piscivorous Brandt’s cormorant, Phalacrocorax penicillatus, was reduced while planktivorous Cassin’s auklet, Ptychoramphus aleuticus was elevated. Differences between the productivity of these two seabirds may be related to the available forage assemblage observed in the surveys. California sea lion pups from San Miguel Island were undernourished resulting in a pup mortality event perhaps in response to changes in forage availability. Limited biological data were available for spring 2013, but strong winter upwelling coastwide indicated an early spring transition, with the strong upwelling persisting into early summer

Seasonal changes in patterns of gene expression in avian song control brain regions.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Photoperiod and hormonal cues drive dramatic seasonal changes in structure and function of the avian song control system. Little is known, however, about the patterns of gene expression associated with seasonal changes. Here we address this issue by altering the hormonal and photoperiodic conditions in seasonally-breeding Gambel's white-crowned sparrows and extracting RNA from the telencephalic song control nuclei HVC and RA across multiple time points that capture different stages of growth and regression. We chose HVC and RA because while both nuclei change in volume across seasons, the cellular mechanisms underlying these changes differ. We thus hypothesized that different genes would be expressed between HVC and RA. We tested this by using the extracted RNA to perform a cDNA microarray hybridization developed by the SoNG initiative. We then validated these results using qRT-PCR. We found that 363 genes varied by more than 1.5 fold (>log(2) 0.585) in expression in HVC and/or RA. Supporting our hypothesis, only 59 of these 363 genes were found to vary in both nuclei, while 132 gene expression changes were HVC specific and 172 were RA specific. We then assigned many of these genes to functional categories relevant to the different mechanisms underlying seasonal change in HVC and RA, including neurogenesis, apoptosis, cell growth, dendrite arborization and axonal growth, angiogenesis, endocrinology, growth factors, and electrophysiology. This revealed categorical differences in the kinds of genes regulated in HVC and RA. These results show that different molecular programs underlie seasonal changes in HVC and RA, and that gene expression is time specific across different reproductive conditions. Our results provide insights into the complex molecular pathways that underlie adult neural plasticity

Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability