Tough Love: The Dramatic Birth and Looming Demise of UNCLOS Property Law (and What Is to Be Done about It)

The 1982 United Nations Convention on the Law of the Sea (“UNCLOS”) represents the culmination of thousands of years of international relations, conflict, and now nearly universal adherence to an enduring order for ocean space that is the most significant achievement for international law since the UN Charter. UNCLOS establishes international property law erga omnes that, by legal and political necessity, required a bargained consensus to be effective. This bargain, in essence, provided coastal States with extended but limited jurisdictions, while ensuring that the seabed and its mineral resources beyond were the “common heritage of mankind” that would peaceably and sustainably benefit all. Yet whether UNCLOS in fact and in law is now living up to this bidding is in doubt. The critical task of delineating a true outer limit to the continental shelf is now a matter of implementing the delicate balance between applied science and supervised unilateral claims embodied in Article 76. The attempt to ‘legalize’ scientific criteria still retains legal vagueness and ambiguities as well as the uncertainties inherent in any nascent scientific endeavor. Further, the administrative and financial support established to assist in working through these challenges has brought its own bureaucratic obstacles. This has led to a near-perfect storm for small island developing States, which rely most heavily on marine resources for their culture and survival yet also face the most complex dilemmas in Article 76—all the while having generally the least capacity available to prepare their submissions. The challenges facing the seabed come not from implementation of a legal process, but from substantive overlap and even conflict between Part XI and other international law. Part XI seems to provide clear grounds to refute the assertion of international patent rights for seabed organisms. This could set the stage for a fragmentation of international intellectual property rights under TRIPS and the UNCLOS seabed regime. And the expansion of bottom trawl fishing that directly impacts and exploits coral and the seabed is excused under high seas fishing freedoms, but could also be viewed as infringing on the basic tenets of the seabed “common heritage” and thus could invoke individual State responsibility or the regulatory jurisdiction of Part XI. At each juncture, as this paper suggests, the necessity of consensus for international property law can also become an effective and constructive tool for encouraging countries to work together on managing the implementation, development, and proliferation of the law of the sea

Stem Cell-Specific Mechanisms Ensure Genomic Fidelity within HSCs and upon Aging of HSCs

SummaryWhether aged hematopoietic stem and progenitor cells (HSPCs) have impaired DNA damage repair is controversial. Using a combination of DNA mutation indicator assays, we observe a 2- to 3-fold increase in the number of DNA mutations in the hematopoietic system upon aging. Young and aged hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) do not show an increase in mutation upon irradiation-induced DNA damage repair, and young and aged HSPCs respond very similarly to DNA damage with respect to cell-cycle checkpoint activation and apoptosis. Both young and aged HSPCs show impaired activation of the DNA-damage-induced G1-S checkpoint. Induction of chronic DNA double-strand breaks by zinc-finger nucleases suggests that HSPCs undergo apoptosis rather than faulty repair. These data reveal a protective mechanism in both the young and aged hematopoietic system against accumulation of mutations in response to DNA damage

Functional Genomics of Chlorine-induced Acute Lung Injury in Mice

Acute lung injury can be induced indirectly (e.g., sepsis) or directly (e.g., chlorine inhalation). Because treatment is still limited to supportive measures, mortality remains high (∼74,500 deaths/yr). In the past, accidental (railroad derailments) and intentional (Iraq terrorism) chlorine exposures have led to deaths and hospitalizations from acute lung injury. To better understand the molecular events controlling chlorine-induced acute lung injury, we have developed a functional genomics approach using inbred mice strains. Various mouse strains were exposed to chlorine (45 ppm × 24 h) and survival was monitored. The most divergent strains varied by more than threefold in mean survival time, supporting the likelihood of an underlying genetic basis of susceptibility. These divergent strains are excellent models for additional genetic analysis to identify critical candidate genes controlling chlorine-induced acute lung injury. Gene-targeted mice then could be used to test the functional significance of susceptibility candidate genes, which could be valuable in revealing novel insights into the biology of acute lung injury

Functional Genomic Assessment of Phosgene-Induced Acute Lung Injury in Mice

In this study, a genetically diverse panel of 43 mouse strains was exposed to phosgene and genome-wide association mapping performed using a high-density single nucleotide polymorphism (SNP) assembly. Transcriptomic analysis was also used to improve the genetic resolution in the identification of genetic determinants of phosgene-induced acute lung injury (ALI). We prioritized the identified genes based on whether the encoded protein was previously associated with lung injury or contained a nonsynonymous SNP within a functional domain. Candidates were selected that contained a promoter SNP that could alter a putative transcription factor binding site and had variable expression by transcriptomic analyses. The latter two criteria also required that ≥10% of mice carried the minor allele and that this allele could account for ≥10% of the phenotypic difference noted between the strains at the phenotypic extremes. This integrative, functional approach revealed 14 candidate genes that included Atp1a1, Alox5, Galnt11, Hrh1, Mbd4, Phactr2, Plxnd1, Ptprt, Reln, and Zfand4, which had significant SNP associations, and Itga9, Man1a2, Mapk14, and Vwf, which had suggestive SNP associations. Of the genes with significant SNP associations, Atp1a1, Alox5, Plxnd1, Ptprt, and Zfand4 could be associated with ALI in several ways. Using a competitive electrophoretic mobility shift analysis, Atp1a1 promoter (rs215053185) oligonucleotide containing the minor G allele formed a major distinct faster-migrating complex. In addition, a gene with a suggestive SNP association, Itga9, is linked to transforming growth factor β1 signaling, which previously has been associated with the susceptibility to ALI in mice

Epistatic Gene-Based Interaction Analyses for Glaucoma in eMERGE and NEIGHBOR Consortium

10.1371/journal.pgen.1006186PLoS Genetics129e100618