Integrated assessment of oyster reef ecosystem services: Macrofauna utilization of restored oyster reefs

Within the Harris Creek Oyster Sanctuary in the Maryland portion of Chesapeake Bay, we evaluated relationships between basic oyster reef characteristics and the abundance and biomass of macrofauna. The eight sites selected for these studies included five restored oyster reef sites and three sites suitable for restoration that had not been restored. These sites encompassed a range of oyster biomass density and were spread throughout the sanctuary area. At each site one month prior to each of four sampling periods, divers filled four wire mesh baskets (0.1m2 surface area x 15 cm depth) with material from the site and embedded them so that the surface was flush with the surrounding substratum. In spring, early summer, late summer and fall of 2015, divers collected baskets and returned them to the laboratory where all macrofauna ≥1 mm were collected from each sample and their identity, abundance and biomass were determined. In addition to the abundance and biomass of oysters, we also assessed the amount of surface as the volume of live oysters along with that of any oyster shells whose surface was at least 50% oxic based on coloration (i.e. black shell was presumed to have been buried below the surface in anoxic conditions). Positive relationships were identified for all three reef characteristics and the three major macrofaunal groups examined. In the majority of seasons, the relationship between both biomass and abundance of the hooked mussel, Ischadium recurvum, as a power function of oyster tissue biomass density, oyster abundance per square meter and surface shell volume. The relationship between oyster reef characteristics and the biomass and abundance of the mud crab, Eurypanopeus depressus, and of the naked goby, Gobiosoma bosc, were always positive but were more variable than that for I. recurvum. These data demonstrate that relationships can be found between oyster reef characteristics and macrofauna abundance and biomass. They further demonstrate that, in many cases, simple measures of reef characteristics such as oyster abundance and shell volume can provide predictions of macrofauna abundance and biomass that are comparable to more labor intensive measures such as oyster tissue biomass

Challenges in developing a cross-serotype rhinovirus vaccine

A great burden of disease is attributable to human rhinovirus (HRV) infections which are the major cause of the common cold, exacerbations of both asthma and chronic obstructive pulmonary disease (COPD), and are associated with asthma development. Despite this there is currently no vaccine for HRV. The first vaccine studies showed some promise in terms of serotype-specific protection against cold symptoms, but antigenic heterogeneity amongst the >150 HRVs has been regarded as a major barrier to effective vaccine development and has resulted in little progress over 50 years. Here we review those vaccine studies conducted to date, discuss the difficulties posed by antigenic heterogeneity and describe some recent advances in generating cross-reactive antibodies and T cell responses using peptide immunogens

Coagulation Factor Xa Induces Proinflammatory Responses in Cardiac Fibroblasts via Activation of Protease-Activated Receptor-1

Coagulation factor (F) Xa induces proinflammatory responses through activation of protease-activated receptors (PARs). However, the effect of FXa on cardiac fibroblasts (CFs) and the contribution of PARs in FXa-induced cellular signalling in CF has not been fully characterised. To answer these questions, human and rat CFs were incubated with FXa (or TRAP-14, PAR-1 agonist). Gene expression of pro-fibrotic and proinflammatory markers was determined by qRT-PCR after 4 and 24 h. Gene silencing of F2R (PAR-1) and F2RL1 (PAR-2) was achieved using siRNA. MCP-1 protein levels were measured by ELISA of FXa-conditioned media at 24 h. Cell proliferation was assessed after 24 h of incubation with FXa ± SCH79797 (PAR-1 antagonist). In rat CFs, FXa induced upregulation of Ccl2 (MCP-1; >30-fold at 4 h in atrial and ventricular CF) and Il6 (IL-6; ±7-fold at 4 h in ventricular CF). Increased MCP-1 protein levels were detected in FXa-conditioned media at 24 h. In human CF, FXa upregulated the gene expression of CCL2 (>3-fold) and IL6 (>4-fold) at 4 h. Silencing of F2R (PAR-1 gene), but not F2RL1 (PAR-2 gene), downregulated this effect. Selective activation of PAR-1 by TRAP-14 increased CCL2 and IL6 gene expression; this was prevented by F2R (PAR-1 gene) knockdown. Moreover, SCH79797 decreased FXa-induced proliferation after 24 h. In conclusion, our study shows that FXa induces overexpression of proinflammatory genes in human CFs via PAR-1, which was found to be the most abundant PARs isoform in this cell type

Verification of the Crooks fluctuation theorem and recovery of RNA folding free energies

The description of nonequilibrium processes in nano-sized objects, where the typical energies involved are a few times, is increasingly becoming central to disciplines as diverse as condensed-matter physics, materials science, and biophysics. Major recent developments towards a unified treatment of arbitrarily large fluctuations in small systems are described by fluctuation theorems that relate the probabilities of a system absorbing from or releasing to the bath a given amount of energy in a nonequilibrium process. Here we experimentally verify the Crooks Fluctuation Theorem (CFT) under weak and strong nonequilibrium conditions by using optical tweezers to measure the irreversible mechanical work during the unfolding and refolding of a small RNA hairpin and an RNA three-helix junction. We also show that the CFT provides a powerful way to obtain folding free energies in biomolecules by determining the crossing between the unfolding and refolding irreversible work distributions. The method makes it possible to obtain folding free energies in nonequilibrium processes that dissipate up to of the average total work exerted, thereby paving the way for reconstructing free energy landscapes along reaction coordinates in nonequilibrium single-molecule experiments.Comment: PDF file, 19 pages. Supplementary information available online at www.nature.co

Design, synthesis, and analysis of conformationally constrained nucleic acids

In this review I discuss straightforward and general methods to modify nucleic acid structure with disulfide cross-links. A motivating factor in developing this chemistry was the notion that disulfide bonds would be excellent tools to probe the structure, dynamics, thermodynamics, folding, and function of DNA and RNA, much in the way that cystine cross-links have been used to study proteins. The chemistry described has been used to synthesize disulfide cross-linked hairpins and duplexes, higher order structures like triplexes, nonground-state conformations, and tRNAs. Since the cross-links form quantitatively by mild air oxidation and do not perturb either secondary or tertiary structure, this modification should prove quite useful for the study of nucleic acids. © 1998 John Wiley & Sons, Inc. Biopoly 48: 83–96, 1998Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37876/1/8_ftp.pd

Executive functions deficits impair extinction of generalization of fear of movement‐related pain

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Background Generalization of fear of movement‐related pain across novel but similar movements can lead to fear responses to movements that are actually not associated with pain. The peak‐shift effect describes a phenomenon whereby particular novel movements elicit even greater fear responses than the original pain‐provoking movement (CS+), because they represent a more extreme version of the CS+. There is great variance in the propensity to generalize as well as the speed of extinction learning when these novel movements are not followed by pain. It can be argued that this variance may be associated with executive function capacity, as individuals may be unable to intentionally inhibit fear responses. This study examined whether executive function capacity contributes to generalization and extinction of generalization as well as peak‐shift of conditioned fear of movement‐related pain and expectancy. Methods Healthy participants performed a proprioceptive fear conditioning task. Executive function tests assessing updating, switching, and inhibition were used to predict changes in (extinction of) fear of movement‐related pain and pain expectancy generalization. Results Low inhibitory capacity was associated with slower extinction of generalized fear of movement‐related pain and pain expectancy. Evidence was found in favor of an area‐shift, rather than a peak‐shift effect, which implies that the peak conditioned fear response extended to, but did not shift to a novel stimulus. Conclusions Participants with low inhibitory capacity may have difficulties withholding fear responses, leading to a slower decrease of generalized fear over time. The findings may be relevant to inform treatments. Significance Low inhibitory capacity is not associated with slower generalization, but extinction of fear generalization. Fear elicited by a novel safe movement, situated outside the CS+/− continuum on the CS+ side, can be as strong as to the original stimulus predicting the pain‐onset

Long-Term Benefits from Early Antiretroviral Therapy Initiation in HIV Infection

BACKGROUND: For people with HIV and CD4+ counts >500 cells/mm3, early initiation of antiretroviral therapy (ART) reduces serious AIDS and serious non-AIDS (SNA) risk compared with deferral of treatment until CD4+ counts are 500 cells/mm3, excess risk of AIDS and SNA associated with delaying treatment initiation was diminished after ART initiation, but persistent excess risk remained. (Funded by the National Institute of Allergy and Infectious Diseases and others.)

Comparisons between Chemical Mapping and Binding to Isoenergetic Oligonucleotide Microarrays Reveal Unexpected Patterns of Binding to the Bacillus subtilis RNase P RNA Specificity Domain†

ABSTRACT: Microarrays with isoenergetic pentamer and hexamer 20-O-methyl oligonucleotide probes with LNA (locked nucleic acid) and 2,6-diaminopurine substitutions were used to probe the binding sites on theRNase P RNA specificity domain of Bacillus subtilis. Unexpected binding patterns were revealed. Because of their enhanced binding free energies, isoenergetic probes can break short duplexes, merge adjacent loops, and/or induce refolding. This suggests new approaches to the rational design of short oligonucleotide therapeutics but limits the utility of microarrays for providing constraints for RNA structure determination. The microarray results are compared to results from chemical mapping experiments, which do provide constraints. Results from both types of experiments indicate that the RNase P RNA folds similarly in 1MNaþ and 10 mMMg2þ. Binding of RNA to RNA is important for many natural func-tions, includingproteinsynthesis (1,2), translationregulation (3,4), gene silencing (5, 6), metabolic regulation (7), RNAmodification (8, 9), etc. (10-13). Binding of oligonucleotides toRNAs is impor-tant for therapeutic approaches, such as siRNA, ribozymes, and antisense therapy (14, 15).Much remains to bediscovered, however, of the rules for predicting binding sites andpotential therapeutics