Utility of antiPax5 in the diagnosis of lymphoproliferative disorders and neoplasia in mice

CD45R/B220 antigen (B220) is a common mouse panB-cell marker used for paraffin-embedded tissues. However, antiB220 has limited specificity in diagnostic pathology because the B220 antigen is expressed on subsets of cytotoxic T lymphocytes and natural killer cells, on plasmacytic dendritic cells, and on T lymphocytes of mice with the lymphoproliferative disorder associated with Fas (lymphoproliferative mutant mouse, B6.MRL-Fas(lpr/J)) or Fas ligand (generalized lymphoproliferative disease mutant mouse, C3H/ HeJ-Fasl(gld/J) or B6Smn.C3-Fasl(gld/J)). In addition, mouse B lymphocytes vary in the amount of B220 expressed, and some subsets of mouse B lymphocytes do not express B220 at all. In comparison, Pax5 expression (detected by immunohistochemistry using antiPax5) offers greater specificity and sensitivity because of its earlier expression during B-cell differentiation, its ability to detect all committed B cells, and its restriction to the B-cell lineage. Here we describe the use of an antibody to human Pax5 in diagnostic pathology with formalin-fixed, paraffin-embedded mouse tissue.     

CD marker expression profiles of human embryonic stem cells and their neural derivatives,determined using flow-cytometric analysis,reveal a novel CD marker for exclusion of pluripotent stem cells

Human embryonic stem cells (hESCs) are pluripotent cells that can differentiate into neural cell lineages. These neural populations are usually heterogeneous and can contain undifferentiated pluripotent cells that are capable of producing teratomas in cell grafts. The characterization of surface protein profiles of hESCs and their neural derivatives is important to determine the specific markers that can be used to exclude undifferentiated cells from neural populations. In this study, we analyzed the cluster of differentiation (CD) marker expression profiles of seven undifferentiated hESC lines using flow-cytometric analysis and compared their profiles to those of neural derivatives. Stem cell and progenitor marker CD133 and epithelial adhesion molecule marker CD326 were more highly expressed in undifferentiated hESCs, whereas neural marker CD56 (NCAM) and neural precursor marker (chemokine receptor) CD184 were more highly expressed in hESC-derived neural cells. CD326 expression levels were consistently higher in all nondifferentiated hESC lines than in neural cell derivatives. In addition, CD326-positive hESCs produced teratomas in SCID mouse testes, whereas CD362-negative neural populations did not. Thus, CD326 may be useful as a novel marker of undifferentiated hESCs to exclude undifferentiated hESCs from differentiated neural cell populations prior to transplantation.     

Disheveled Hair and Ear (Dhe), a Spontaneous Mouse Lmna Mutation Modeling Human Laminopathies

Background

Investigations of naturally-occurring mutations in animal models provide important insights and valuable disease models. Lamins A and C, along with lamin B, are type V intermediate filament proteins which constitute the proteinaceous boundary of the nucleus. LMNA mutations in humans cause a wide range of phenotypes, collectively termed laminopathies. To identify the mutation and investigate the phenotype of a spontaneous, semi-dominant mutation that we have named Disheveled hair and ear (Dhe), which causes a sparse coat and small external ears in heterozygotes and lethality in homozygotes by postnatal day 10.

Findings

Genetic mapping identified a point mutation in the Lmna gene, causing a single amino acid change, L52R, in the coiled coil rod domain of lamin A and C proteins. Cranial sutures in Dhe/+ mice failed to close. Gene expression for collagen types I and III in sutures was deficient. Skulls were small and disproportionate. Skeletons of Dhe/+ mice were hypomineralized and total body fat was deficient in males. In homozygotes, skin and oral mucosae were dysplastic and ulcerated. Nuclear morphometry of cultured cells revealed gene dose-dependent blebbing and wrinkling.

Conclusion

Dhe mice should provide a useful new model for investigations of the pathogenesis of laminopathies.     

Adapting to Regional Enforcement: Fishing Down the Governance Index

Background

Illegal, Unreported and Unregulated (IUU) fishing is a problem for marine resource managers, leading to depletion of fish stocks and negative impacts on marine ecosystems. These problems are particularly evident in regions with weak governance. Countries responsible for sustainable natural resource management in the Southern Ocean have actively worked to reduce IUU fishing in the region over a period of 15 years, leading to a sequence of three distinct peaks of IUU fishing.

Methodology/Principal Findings

We reviewed existing public records relating to IUU fishing in the Southern Ocean between 1995–2009 and related this information to the governance capacity of flag states responsible for IUU vessels. IUU operators used a number of methods to adapt to enforcement actions, resulting in reduced risks of detection, apprehension and sanctioning. They changed fishing locations, vessel names and flag states, and ports for offloading IUU catches. There was a significant decrease in the proportion of IUU vessels flagged to CCAMLR countries, and a significant decrease in the average governance index of flag states. Despite a decreasing trend of IUU fishing, further actions are hampered by the regional scope of CCAMLR and the governance capacity of responsible states.

Conclusions/Significance

This is the first study of long-term change in the modus operandi of IUU fishing operators, illustrating that IUU operators can adapt to enforcement actions and that such dynamics may lead to new problems elsewhere, where countries have a limited capacity. This outsourcing of problems may have similarities to natural resource extraction in other sectors and in other regions. IUU fishing is the result of a number of factors, and effectively addressing this major challenge to sustainable marine resource extraction will likely require a stronger focus on governance. Highly mobile resource extractors with substantial funds are able to adapt to changing regulations by exploiting countries and regions with limited capacity.