Examples of Global and Regional Laws and Policies Relevant to Addressing the Potential Impacts of Climate Change and Ocean Acidification

Laws and policies relevant to the potential impacts of climate change and ocean acidification on marine species and coastal communities appear at the global and regional level, as well as the national level (see Annex 6)

Functional and Morphological Correlates of Connexin50 Expressed in Xenopus laevis Oocytes

Electrophysiological and morphological methods were used to study connexin50 (Cx50) expressed in Xenopus laevis oocytes. Oocytes expressing Cx50 exhibited a new population of intramembrane particles (9.0 nm in diameter) in the plasma membrane. The particles represented hemichannels (connexin hexamers) because (a) their cross-sectional area could accommodate 24 ± 3 helices, (b) when their density reached 300–400/μm2, they formed complete channels (dodecamers) in single oocytes, and assembled into plaques, and (c) their appearance in the plasma membrane was associated with a whole-cell current, which was activated at low external Ca2+ concentration ([Ca2+]o), and was blocked by octanol and by intracellular acidification. The Cx50 hemichannel density was directly proportional to the magnitude of the Cx50 Ca2+-sensitive current. Measurements of hemichannel density and the Ca2+-sensitive current in the same oocytes suggested that at physiological [Ca2+]o (1–2 mM), hemichannels rarely open. In the cytoplasm, hemichannels were present in ∼0.1-μm diameter “coated” and in larger 0.2–0.5-μm diameter vesicles. The smaller coated vesicles contained endogenous plasma membrane proteins of the oocyte intermingled with 5–40 Cx50 hemichannels, and were observed to fuse with the plasma membrane. The larger vesicles, which contained Cx50 hemichannels, gap junction channels, and endogenous membrane proteins, originated from invaginations of the plasma membrane, as their lumen was labeled with the extracellular marker peroxidase. The insertion rate of hemichannels into the plasma membrane (80,000/s), suggested that an average of 4,000 small coated vesicles were inserted every second. However, insertion of hemichannels occurred at a constant plasma membrane area, indicating that insertion by vesicle exocytosis (60–500 μm2 membranes/s) was balanced by plasma membrane endocytosis. These exocytotic and endocytotic rates suggest that the entire plasma membrane of the oocyte is replaced in ∼24 h

On the satisfaction of backbone-carbonyl lone pairs of electrons in protein structures

Protein structures are stabilized by a variety of noncovalent interactions (NCIs), including the hydrophobic effect, hydrogen bonds, electrostatic forces and van der Waals’ interactions. Our knowledge of the contributions of NCIs, and the interplay between them remains incomplete. This has implications for computational modeling of NCIs, and our ability to understand and predict protein structure, stability, and function. One consideration is the satisfaction of the full potential for NCIs made by backbone atoms. Most commonly, backbone‐carbonyl oxygen atoms located within α‐helices and β‐sheets are depicted as making a single hydrogen bond. However, there are two lone pairs of electrons to be satisfied for each of these atoms. To explore this, we used operational geometric definitions to generate an inventory of NCIs for backbone‐carbonyl oxygen atoms from a set of high‐resolution protein structures and associated molecular‐dynamics simulations in water. We included more‐recently appreciated, but weaker NCIs in our analysis, such as n→π* interactions, Cα‐H bonds and methyl‐H bonds. The data demonstrate balanced, dynamic systems for all proteins, with most backbone‐carbonyl oxygen atoms being satisfied by two NCIs most of the time. Combinations of NCIs made may correlate with secondary structure type, though in subtly different ways from traditional models of α‐ and β‐structure. In addition, we find examples of under‐ and over‐satisfied carbonyl‐oxygen atoms, and we identify both sequence‐dependent and sequence‐independent secondary‐structural motifs in which these reside. Our analysis provides a more‐detailed understanding of these contributors to protein structure and stability, which will be of use in protein modeling, engineering and design

Majority Rule

This article provides a survey of existing studies of majority rule, outlines misconceptions of majority rule, and highlights underexplored fields of research. It argues that the reasons why the minority complies with majority decisions have been underexplored

Diagnostic value of anti-cyclic citrullinated peptide antibodies in Greek patients with rheumatoid arthritis

Background: Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been of diagnostic value in Northern European Caucasian patients with rheumatoid arthritis ( RA). In these populations, anti-CCP antibodies are associated with the HLA-DRB1 shared epitope. We assessed the diagnostic value of anti-CCP antibodies in Greek patients with RA where the HLA shared epitope was reported in a minority of patients. Methods: Using an enzyme-linked immunosorbent assay ( ELISA) (CCP2) kit, we tested anti-CCP antibodies in serum samples from 155 Greek patients with RA, 178 patients with other rheumatic diseases, and 100 blood donors. We also determined rheumatoid factor (RF) and compared it to anti-CCP antibodies for area under the curve (AUC), sensitivity, specificity and likelihood ratios. Results: Sensitivity of anti-CCP2 antibodies and RF for RA was 63.2% and 59.1%, and specificity was 95.0% and 91.2%, respectively. When considered simultaneously, the AUC for anti-CCP antibodies was 0.90 with 95% CI of 0.87 to 0.93 and the AUC for RF was 0.71 with 95% CI of 0.64 to 0.77. The presence of both antibodies increased specificity to 98.2%. Anti-CCP antibodies were positive in 34.9% of RF-negative RA patients. Anti-CCP antibodies showed a correlation with the radiographic joint damage. Anti-CCP-positive RA patients had increased the swollen joint count and serum CRP concentration compared to anti-CCP-negative RA patients (Mann-Whitney U test, p = 0.01, and p < 0.001, respectively). However, no correlation was found between anti-CCP antibodies and DAS28 score ( r = 0.13, p = 0.12). Conclusion: In Greek patients with RA, anti-CCP2 antibodies exhibit a better diagnostic value than RF and a correlation with radiological joint damage and therefore are useful in everyday rheumatology practice

[11C]-DPA-713 and [18F]-DPA-714 as New PET Tracers for TSPO: A Comparison with [11C]-(R)-PK11195 in a Rat Model of Herpes Encephalitis

Background: Activation of microglia cells plays an important role in neurological diseases. Positron emission tomography (PET) with [C-11]-(R)-PK11195 has already been used to visualize activated microglia cells in neurological diseases. However, [C-11]-(R)-PK11195 may not possess the required sensitivity to visualize mild neuroinflammation. In this study, we evaluated the PET tracers [C-11]-DPA-713 and [F-18]-DPA-714 as agents for imaging of activated microglia in a rat model of herpes encephalitis. Materials and Methods: Rats were intranasally inoculated with HSV-1. On day 6 or 7 after inoculation, small animal PET studies were performed to compare [C-11]-(R)-PK11195, [C-11]-DPA-713, and [F-18]-DPA-714. Results: Uptake of [C-11]-DPA-713 in infected brain areas was comparable to that of [C-11]-(R)-PK11195, but [C-11]-DPA-713 showed lower non-specific binding. Non-specific uptake of [F-18]-DPA-714 was lower than that of [C-11]-(R)-PK11195. In the infected brain, total [F-18]-DPA-714 uptake was lower than that of [C-11]-(R)-PK11195, with comparable specific uptake. Conclusions: [C-11]-DPA-713 may be more suitable for visualizing mild inflammation than [C-11]-(R)-PK11195. In addition, the fact that [F-18]-DPA-714 is an agonist PET tracer opens new possibilities to evaluate different aspects of neuroinflammation. Therefore, both tracers warrant further investigation in animal models and in a clinical setting

The Subsystems Approach to Genome Annotation and its Use in the Project to Annotate 1000 Genomes

The release of the 1000(th) complete microbial genome will occur in the next two to three years. In anticipation of this milestone, the Fellowship for Interpretation of Genomes (FIG) launched the Project to Annotate 1000 Genomes. The project is built around the principle that the key to improved accuracy in high-throughput annotation technology is to have experts annotate single subsystems over the complete collection of genomes, rather than having an annotation expert attempt to annotate all of the genes in a single genome. Using the subsystems approach, all of the genes implementing the subsystem are analyzed by an expert in that subsystem. An annotation environment was created where populated subsystems are curated and projected to new genomes. A portable notion of a populated subsystem was defined, and tools developed for exchanging and curating these objects. Tools were also developed to resolve conflicts between populated subsystems. The SEED is the first annotation environment that supports this model of annotation. Here, we describe the subsystem approach, and offer the first release of our growing library of populated subsystems. The initial release of data includes 180 177 distinct proteins with 2133 distinct functional roles. This data comes from 173 subsystems and 383 different organisms