Active bacterioplankton community response to dissolved ‘free’ deoxyribonucleic acid (dDNA) in surface coastal marine waters

Seawater contains dissolved ‘free’ DNA (dDNA) that is part of a larger <0.2 μm pool of DNA (D-DNA) including viruses and uncharacterised bound DNA. Previous studies have shown that bacterioplankton readily degrade dDNA and culture-based approaches have identified several potential dDNA-utilising taxa. This study characterised the seasonal variation in D-DNA concentrations at Station L4, a coastal marine observatory in the Western English Channel, and linked changes in concentration to cognate physicochemical and biological factors. The impact of dDNA addition on active bacterioplankton communities at Station L4 was then determined using 16S rRNA high-throughput sequencing and RNA Stable Isotope Probing (RNA SIP) with 13C-labelled diatom-derived dDNA. Compared to other major bacterioplankton orders, the Rhodobacterales actively responded to dDNA additions in amended microcosms and RNA SIP identified two Rhodobacterales populations most closely associated with the genera Halocynthiibacter and Sulfitobacter that assimilated the 13C-labelled dDNA. Here we demonstrate that dDNA is a source of dissolved organic carbon for some members of the major bacterioplankton group the Marine Roseobacter Clade. This study enhances our understanding of roles of specific bacterioplankton taxa in dissolved organic matter cycling in coastal waters with potential implications for nitrogen and phosphorus regeneration processes

Gamma-Ray Telescopes (in "400 Years of Astronomical Telescopes")

The last half-century has seen dramatic developments in gamma-ray telescopes, from their initial conception and development through to their blossoming into full maturity as a potent research tool in astronomy. Gamma-ray telescopes are leading research in diverse areas such as gamma-ray bursts, blazars, Galactic transients, and the Galactic distribution of aluminum-26.Comment: 11 pages, 6 figures/ in "400 Years of Astronomical Telescopes: A Review of History, Science and Technology", ed. B.R. Brandl, R. Stuik, & J.K. Katgert-Merkeli (Exp. Astron. 26, 111-122 [2009]

Transport phenomena in electrolyte solutions: Non-equilibrium thermodynamics and statistical mechanics

The theory of transport phenomena in multicomponent electrolyte solutions is presented here through the integration of continuum mechanics, electromagnetism, and non-equilibrium thermodynamics. The governing equations of irreversible thermodynamics, including balance laws, Maxwell's equations, internal entropy production, and linear laws relating the thermodynamic forces and fluxes, are derived. Green-Kubo relations for the transport coefficients connecting electrochemical potential gradients and diffusive fluxes are obtained in terms of the flux-flux time correlations. The relationship between the derived transport coefficients and those of the Stefan-Maxwell and infinitely dilute frameworks are presented, and the connection between the transport matrix and experimentally measurable quantities is described. To exemplify application of the derived Green-Kubo relations in molecular simulations, the matrix of transport coefficients for lithium and chloride ions in dimethyl sulfoxide is computed using classical molecular dynamics and compared with experimental measurements.Comment: fixed typos, added references, addressed comment

Bayesian paternity analysis and mating patterns in a parasitic nematode, Trichostrongylus tenuis

Mating behaviour is a fundamental aspect of the evolutionary ecology of sexually reproducing species, but one that has been under-researched in parasitic nematodes. We analysed mating behaviour in the parasitic nematode Trichostrongylus tenuis by performing a paternity analysis in a population from a single red grouse host. Paternity of the 150 larval offspring of 25 mothers (sampled from one of the two host caeca) was assigned among 294 candidate fathers (sampled from both caeca). Each candidate father's probability of paternity of each offspring was estimated from 10-locus microsatellite genotypes. Seventy-six (51%) offspring were assigned a father with a probability of >0.8, and the estimated number of unsampled males was 136 (95% credible interval (CI) 77-219). The probability of a male from one caecum fathering an offspring in the other caecum was estimated as 0.024 (95% CI 0.003-0.077), indicating that the junction of the caeca is a strong barrier to dispersal. Levels of promiscuity (defined as the probability of two of an adult's offspring sharing only one parent) were high for both sexes. Variance in male reproductive success was moderately high, possibly because of a combination of random mating and high variance in post-copulatory reproductive success. These results provide the first data on individual mating behaviour among parasitic nematodes

Truncated and Helix-Constrained Peptides with High Affinity and Specificity for the cFos Coiled-Coil of AP-1

Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i-->i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, alpha-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable alpha-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJun–cFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased conformational entropy (TDS ≤ 7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by alpha-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases

Atlas of the OMERACT Heel Enthesitis MRI Scoring System (HEMRIS)

Objective: Assessment of enthesitis, a key feature in spondyloarthritis (SpA) and psoriatic arthritis (PsA), using objective and sensitive methods is pivotal in clinical trials. MRI allows detection of both soft tissue and intra-osseous changes of enthesitis. This article presents an atlas for the Outcome Measures in Rheumatology (OMERACT) Heel Enthesitis Magnetic Resonance ImagingMRI Scoring System (HEMRIS). Methods: Following a preliminary selection of potential examples of each grade, as per HEMRIS definitions, the images along with detailed definitions and reader rules were discussed at web-based, interactive meetings between the members of the OMERACT MRI in Arthritis Working Group. Results: Reference images of each grade of the MRI features to be assessed using HEMRIS, along with reader rules and recommended MRI sequences are depicted. Conclusion: The presented reference images can be used to guide scoring Achilles tendon and plantar fascia (plantar aponeurosis) enthesitis according to the OMERACT HEMRIS in clinical trials and cohorts in which MRI enthesitis is used as an outcome

Young women's use of a microbicide surrogate: The complex influence of relationship characteristics and perceived male partners' evaluations

This is the post-print version of the article. The official published version can be found at the link below.Currently in clinical trials, vaginal microbicides are proposed as a female-initiated method of sexually transmitted infection prevention. Much of microbicide acceptability research has been conducted outside of the United States and frequently without consideration of the social interaction between sex partners, ignoring the complex gender and power structures often inherent in young women’s (heterosexual) relationships. Accordingly, the purpose of this study was to build on existing microbicide research by exploring the role of male partners and relationship characteristics on young women’s use of a microbicide surrogate, an inert vaginal moisturizer (VM), in a large city in the United States. Individual semi-structured interviews were conducted with 40 young women (18–23 years old; 85% African American; 47.5% mothers) following use of the VM during coital events for a 4 week period. Overall, the results indicated that relationship dynamics and perceptions of male partners influenced VM evaluation. These two factors suggest that relationship context will need to be considered in the promotion of vaginal microbicides. The findings offer insights into how future acceptability and use of microbicides will be influenced by gendered power dynamics. The results also underscore the importance of incorporating men into microbicide promotion efforts while encouraging a dialogue that focuses attention on power inequities that can exist in heterosexual relationships. Detailed understanding of these issues is essential for successful microbicide acceptability, social marketing, education, and use.This study was funded by a grant from National Institutes of Health (NIHU19AI 31494) as well as research awards to the first author: Friends of the Kinsey Institute Research Grant Award, Indiana University’s School of HPER Graduate Student Grant-in-Aid of Research Award, William L. Yarber Sexual Health Fellowship, and the Indiana University Graduate and Professional Student Organization Research Grant

MFGE8 does not influence chorio-retinal homeostasis or choroidal neovascularization in vivo

Purpose: Milk fat globule-epidermal growth factor-factor VIII (MFGE8) is necessary for diurnal outer segment phagocytosis and promotes VEGF-dependent neovascularization. The prevalence of two single nucleotide polymorphisms (SNP) in MFGE8 was studied in two exsudative or “wet” Age-related Macular Degeneration (AMD) groups and two corresponding control groups. We studied the effect of MFGE8 deficiency on retinal homeostasis with age and on choroidal neovascularization (CNV) in mice. Methods: The distribution of the SNP (rs4945 and rs1878326) of MFGE8 was analyzed in two groups of patients with “wet” AMD and their age-matched controls from Germany and France. MFGE8-expressing cells were identified in Mfge8+/− mice expressing ß-galactosidase. Aged Mfge8+/− and Mfge8−/− mice were studied by funduscopy, histology, electron microscopy, scanning electron microscopy of vascular corrosion casts of the choroid, and after laser-induced CNV. Results: rs1878326 was associated with AMD in the French and German group. The Mfge8 promoter is highly active in photoreceptors but not in retinal pigment epithelium cells. Mfge8−/− mice did not differ from controls in terms of fundus appearance, photoreceptor cell layers, choroidal architecture or laser-induced CNV. In contrast, the Bruch's membrane (BM) was slightly but significantly thicker in Mfge8−/− mice as compared to controls. Conclusions: Despite a reproducible minor increase of rs1878326 in AMD patients and a very modest increase in BM in Mfge8−/− mice, our data suggests that MFGE8 dysfunction does not play a critical role in the pathogenesis of AMD

Intragenic DNA methylation: implications of this epigenetic mechanism for cancer research

Epigenetics is the study of all mechanisms that regulate gene transcription and genome stability that are maintained throughout the cell division, but do not include the DNA sequence itself. The best-studied epigenetic mechanism to date is DNA methylation, where methyl groups are added to the cytosine base within cytosine–guanine dinucleotides (CpG sites). CpGs are frequently clustered in high density (CpG islands (CGIs)) at the promoter of over half of all genes. Current knowledge of transcriptional regulation by DNA methylation centres on its role at the promoter where unmethylated CGIs are present at most actively transcribed genes, whereas hypermethylation of the promoter results in gene repression. Over the last 5 years, research has gradually incorporated a broader understanding that methylation patterns across the gene (so-called intragenic or gene body methylation) may have a role in transcriptional regulation and efficiency. Numerous genome-wide DNA methylation profiling studies now support this notion, although whether DNA methylation patterns are a cause or consequence of other regulatory mechanisms is not yet clear. This review will examine the evidence for the function of intragenic methylation in gene transcription, and discuss the significance of this in carcinogenesis and for the future use of therapies targeted against DNA methylation

Diversity of Tanaidacea (Crustacea: Peracarida) in the World's Oceans – How Far Have We Come?

Tanaidaceans are small peracarid crustaceans which occur in all marine habitats, over the full range of depths, and rarely into fresh waters. Yet they have no obligate dispersive phase in their life-cycle. Populations are thus inevitably isolated, and allopatric speciation and high regional diversity are inevitable; cosmopolitan distributions are considered to be unlikely or non-existent. Options for passive dispersion are discussed. Tanaidaceans appear to have first evolved in shallow waters, the region of greatest diversification of the Apseudomorpha and some tanaidomorph families, while in deeper waters the apseudomorphs have subsequently evolved two or three distinct phyletic lines. The Neotanaidomorpha has evolved separately and diversified globally in deep waters, and the Tanaidomorpha has undergone the greatest evolution, diversification and adaptation, to the point where some of the deep-water taxa are recolonizing shallow waters. Analysis of their geographic distribution shows some level of regional isolation, but suffers from inclusion of polyphyletic taxa and a general lack of data, particularly for deep waters. It is concluded that the diversity of the tanaidomorphs in deeper waters and in certain ocean regions remains to be discovered; that the smaller taxa are largely understudied; and that numerous cryptic species remain to be distinguished. Thus the number of species currently recognized is likely to be an order of magnitude too low, and globally the Tanaidacea potentially rival the Amphipoda and Isopoda in diversity