How Much Longer Will it Take? A Ten-year Review of the Implementation of United Nations General Assembly Resolutions 61/105, 64/72 and 66/68 on the Management of Bottom Fisheries in Areas Beyond National Jurisdiction

The United Nations General Assembly (UNGA) in 2002 adopted the first in a series of resolutions regarding the conservation of biodiversity in the deep sea. Prompted by seriousconcerns raised by scientists, non-governmental organizations (NGOs) and numerous States,these resolutions progressively committed States to act both individually and through regional fishery management organizations (RFMOs) to either manage bottom fisheries in areas beyond national jurisdiction to prevent significant adverse impacts on deep-sea species, ecosystems and biodiversity or else prohibit bottom fishing from taking place.Ten years have passed since the adoption of resolution 61/105 in 2006, calling on States to take a set of specific actions to manage bottom fisheries in areas beyond national jurisdiction to protect vulnerable marine ecosystems (VMEs) from the adverse impacts of bottom fishing and ensure the sustainability of deep-sea fish stocks. Despite the considerable progress by some RFMOs, there remain significant gaps in the implementation of key elements and commitments in the resolutions. The Deep Sea Conservation Coalition (DSCC) has prepared this report to assist the UNGA in its review in 2016 and to address the following question: How effectively have the resolutions been implemented

Unfinished Business: a Review of the Implementation of the Provisions of United Nations General Assembly Resolutions 61/105 and 64/72, Related to the Management of Bottom Fisheries in Areas Beyond National Jurisdiction

In 2006 the General Assembly adopted resolution 61/105, based on a compromise proposal offered by deep-sea fishing nations, which committed States and regional fisheries management organisations [RFMOs] to take specific measures to protect vulnerable marine ecosystems [VMEs] from the adverse impacts of bottom fisheries in the high seas and to ensure the longterm sustainability of deep-sea fish stocks. These measures included conducting impact assessments to determine whether significant adverse impacts[SAIs] to VMEs would occur, managing fisheries to prevent SAIs on VMEs, and closing areas of the high seas to bottom fishing where VMEs are known or likely to occur, unless regulations are in place to prevent SAIs and to manage sustainably deep-sea fish stocks. Based on a review in 2009 of the actions taken by States and RFMOS, the UNGA adoptedresolution 64/72 that reaffirmed resolution 61/105 and strengthened the call for action through committing States, inter alia, to ensure that vessels do not engage in bottom fishing until impact assessments have been carried out and to not authorise bottom fishing activities until the measures in resolutions 64/72 and 61/105 have been adopted andimplemented

Drug design and synthesis of first in class PDZ1 targeting NHERF1 inhibitors as anticancer agents

Targeted approaches aiming at modulating NHERF1 activity, rather than its overall expression, would be preferred to preserve the normal functions of this versatile protein. We focused our attention on the NHERF1/PDZ1 domain that governs its membrane recruitment/displacement through a transient phosphorylation switch. We herein report the design and synthesis of novel NHERF1 PDZ1 domain inhibitors. These compounds have potential therapeutic value when used in combination with antagonists of β-catenin to augment apoptotic death of colorectal cancer cells refractory to currently available Wnt/β-catenin-targeted agents

Folding mechanisms steer the amyloid fibril formation propensity of highly homologous proteins

Significant advances in the understanding of the molecular determinants of fibrillogenesis can be expected from comparative studies of the aggregation propensities of proteins with highly homologous structures but different folding pathways. Here, we fully characterize, by means of stopped-flow, T-jump, CD and DSC experiments, the unfolding mechanisms of three highly homologous proteins, zinc binding Ros87 and Ml153-149 and zinc-lacking Ml452-151. The results indicate that the three proteins significantly differ in terms of stability and (un)folding mechanisms. Particularly, Ros87 and Ml153-149 appear to be much more stable to guanidine denaturation and are characterized by folding mechanisms including the presence of an intermediate. On the other hand, metal lacking Ml452-151 folds according to a classic two-state model. Successively, we have monitored the capabilities of Ros87, Ml452-151 and Ml153-149 to form amyloid fibrils under native conditions. Particularly, we show, by CD, fluorescence, DLS, TEM and SEM experiments, that after 168 hours, amyloid formation of Ros87 has started, while Ml153-149 has formed only amorphous aggregates and Ml452-151 is still monomeric in solution. This study shows how metal binding can influence protein folding pathways and thereby control conformational accessibility to aggregation-prone states, which in turn changes aggregation kinetics, shedding light on the role of metal ions in the development of protein deposition diseases

Selection and characterization of a promoter for expression of single-copy recombinant genes in Gram-positive bacteria

BACKGROUND: In the past ten years there has been a growing interest in engineering Gram-positive bacteria for biotechnological applications, including vaccine delivery and production of recombinant proteins. Usually, bacteria are manipulated using plasmid expression vectors. The major limitation of this approach is due to the fact that recombinant plasmids are often lost from the bacterial culture upon removal of antibiotic selection. We have developed a genetic system based on suicide vectors on conjugative transposons allowing stable integration of recombinant DNA into the chromosome of transformable and non-transformable Gram-positive bacteria. RESULTS: The aim of this work was to select a strong chromosomal promoter from Streptococcus gordonii to improve this genetic system making it suitable for expression of single-copy recombinant genes. To achieve this task, a promoterless gene encoding a chloramphenicol acetyltransferase (cat), was randomly integrated into the S. gordonii chromosome and transformants were selected for chloramphenicol resistance. Three out of eighteen chloramphenicol resistant transformants selected exhibited 100% stability of the phenotype and only one of them, GP215, carried the cat gene integrated as a single copy. A DNA fragment of 600 base pairs exhibiting promoter activity was isolated from GP215 and sequenced. The 5' end of its corresponding mRNA was determined by primer extention analysis and the putative -10 and a -35 regions were identified. To study the possibility of using this promoter (PP) for single copy heterologous gene expression, we created transcriptional fusions of PP with genes encoding surface recombinant proteins in a vector capable of integrating into the conjugative transposon Tn916. Surface recombinant proteins whose expression was controlled by the PP promoter were detected in Tn916-containing strains of S. gordonii and Bacillus subtilis after single copy chromosomal integration of the recombinant insertion vectors into the resident Tn916. The surface recombinant protein synthesized under the control of PP was also detected in Enterococcus faecalis after conjugal transfer of a recombinant Tn916 containing the transcriptional fusion. CONCLUSION: We isolated and characterized a S. gordonii chromosomal promoter. We demonstrated that this promoter can be used to direct expression of heterologous genes in different Gram-positive bacteria, when integrated in a single copy into the chromosome

Freezing transition of the vortex liquid in anisotropic superconductors

We study the solid-liquid transition of a model of pancake vortices in laminar superconductors using a density functional theory of freezing. The physical properties of the system along the melting line are discussed in detail. We show that there is a very good agreement with experimental data in the shape and position of the first order transition in the phase diagram and in the magnitude and temperature dependence of the magnetic induction jump at the transition. We analyze the validity of the Lindemann melting criterion and the Hansen-Verlet freezing criterion. Both criteria are shown to be good to predict the phase diagram in the region where a first order phase transition is experimentally observed.Comment: 9 pages, 10 figure

Templated folding of intrinsically disordered proteins

Much of our current knowledge of biological chemistry is founded in the structure-function relationship, whereby sequence determines structure that determines function. Thus, the discovery that a large fraction of the proteome is intrinsically disordered, while being functional, has revolutionized our understanding of proteins and raised new and interesting questions. Many intrinsically disordered proteins (IDPs) have been determined to undergo a disorder-to-order transition when recognizing their physiological partners, suggesting that their mechanisms of folding are intrinsically different from those observed in globular proteins. However, IDPs also follow some of the classic paradigms established for globular proteins, pointing to important similarities in their behavior. In this review, we compare and contrast the folding mechanisms of globular proteins with the emerging features of binding-induced folding of intrinsically disordered proteins. Specifically, whereas disorder-to-order transitions of intrinsically disordered proteins appear to follow rules of globular protein folding, such as the cooperative nature of the reaction, their folding pathways are remarkably more malleable, due to the heterogeneous nature of their folding nuclei, as probed by analysis of linear free-energy relationship plots. These insights have led to a new model for the disorder-to-order transition in IDPs termed “templated folding,” whereby the binding partner dictates distinct structural transitions en route to product, while ensuring a cooperative folding