Centralized Modularity of N-Linked Glycosylation Pathways in Mammalian Cells

Glycosylation is a highly complex process to produce a diverse repertoire of cellular glycans that are attached to proteins and lipids. Glycans are involved in fundamental biological processes, including protein folding and clearance, cell proliferation and apoptosis, development, immune responses, and pathogenesis. One of the major types of glycans, N-linked glycans, is formed by sequential attachments of monosaccharides to proteins by a limited number of enzymes. Many of these enzymes can accept multiple N-linked glycans as substrates, thereby generating a large number of glycan intermediates and their intermingled pathways. Motivated by the quantitative methods developed in complex network research, we investigated the large-scale organization of such N-linked glycosylation pathways in mammalian cells. The N-linked glycosylation pathways are extremely modular, and are composed of cohesive topological modules that directly branch from a common upstream pathway of glycan synthesis. This unique structural property allows the glycan production between modules to be controlled by the upstream region. Although the enzymes act on multiple glycan substrates, indicating cross-talk between modules, the impact of the cross-talk on the module-specific enhancement of glycan synthesis may be confined within a moderate range by transcription-level control. The findings of the present study provide experimentally-testable predictions for glycosylation processes, and may be applicable to therapeutic glycoprotein engineering

Geographic patterns of genetic variation in a broadly distributed marine vertebrate: new insights into loggerhead turtle stock structure from expanded mitochondrial DNA sequences

Previous genetic studies have demonstrated that natal homing shapes the stock structure of marine turtle nesting populations. However, widespread sharing of common haplotypes based on short segments of the mitochondrial control region often limits resolution of the demographic connectivity of populations. Recent studies employing longer control region sequences to resolve haplotype sharing have focused on regional assessments of genetic structure and phylogeography. Here we synthesize available control region sequences for loggerhead turtles from the Mediterranean Sea, Atlantic, and western Indian Ocean basins. These data represent six of the nine globally significant regional management units (RMUs) for the species and include novel sequence data from Brazil, Cape Verde, South Africa and Oman. Genetic tests of differentiation among 42 rookeries represented by short sequences (380 bp haplotypes from 3,486 samples) and 40 rookeries represented by long sequences (~800 bp haplotypes from 3,434 samples) supported the distinction of the six RMUs analyzed as well as recognition of at least 18 demographically independent management units (MUs) with respect to female natal homing. A total of 59 haplotypes were resolved. These haplotypes belonged to two highly divergent global lineages, with haplogroup I represented primarily by CC-A1, CC-A4, and CC-A11 variants and haplogroup II represented by CC-A2 and derived variants. Geographic distribution patterns of haplogroup II haplotypes and the nested position of CC-A11.6 from Oman among the Atlantic haplotypes invoke recent colonization of the Indian Ocean from the Atlantic for both global lineages. The haplotypes we confirmed for western Indian Ocean RMUs allow reinterpretation of previous mixed stock analysis and further suggest that contemporary migratory connectivity between the Indian and Atlantic Oceans occurs on a broader scale than previously hypothesized. This study represents a valuable model for conducting comprehensive international cooperative data management and research in marine ecology

On the number of purkinje cells in the human cerebellum: Unbiased estimates obtained by using the “fractionator”

Stereological estimates of the numbers of Purkinje cell nucleoli in human cerebellar cortex have been obtained from systematic random samples of tissue by using the fractionator. The estimates are unbiased by fixation, section thickness, or sampling errors and are independent of any assumptions about cell shape, size, or spatial orientation. Twelve brains from aged subjects of both sexes were examined. The average complement of nucleoli in four female brains (age range 71–93 years) amounted to 14.8 millions (with an observed coefficient of variation between subjects of 29%). For three male brains (76–91 years), the corresponding estimates were 15.7 millions (10%). No significant sex differences were found for these small samples. Five brains of unknown sex and age yielded values of 15.8 millions (18%). For the twelve brains examined, the total number of Purkinje cell nucleoli per cerebellum was found to be 15.4 millions (19%). Estimated numbers showed a significant positive correlation with cerebellar weights. The number of nucleoli in an individual cerebellum was obtained with high precision in as short a time as 4 hours

Isolation And Characterization Of Tetranucleotide Microsatellites From The Leatherback Turtle (Dermochelys Coriacea)

The leatherback turtle (Dermochelys coriacea) is a globally endangered marine species. Numerous questions regarding life history and demographics that are of conservation interest remain and many of these can be addressed through the use of highly polymorphic nuclear markers. We describe primers and polymerase chain reaction conditions to amplify 19 tetranucleotide microsatellite loci from the leatherback turtle. The primers were tested on samples from 22 females that nested at Archie Carr National Wildlife Refuge, Melbourne Beach, Florida, USA. The primers developed in this study yielded an average of 9.4 alleles per locus (range of 5-19) and an average observed heterozygosity of 0.84 (range 0.36-1.00). These markers should prove useful in supplementing existing markers for individual and population level analyses. © Springer Science+Business Media B.V. 2011

Crowning glory: public law, power and the monarchy

‘New public law’ has a keen interest in the deployment of power and the shifting nature of the public and private. In this article, we argue that the historical legacy of the Crown has hindered the ability of public lawyers to respond to changes in modes of governance in the UK. The constitutional law textbook tradition has played a key role in limiting critiques of the Crown because of the obfuscation that surrounds the legal and political status of the Monarch. However, instead of discounting the significance of the monarchy, we use it as a resource for exploring governing power, the blurring of boundaries and constitutional renewal. Our starting point is the life, death and, most importantly, the funeral of Diana, Princess of Wales. The latter event exposed the political relevance of the ‘personal’ in a most dramatic way, generating claims about the ‘feminisation of the government’ and ‘emotions augmenting democracy’. We follow through on these claims in order to focus on the effects of adopting private, intimate-sphere norms in the public sphere, in particular public-sphere decision making. While aware of the risks associated with this ‘transformation’ of democracy, we conclude that the increasing centrality of the intimate merits onsideration in new public law’s search for progressive tools of modern governance

Tetranucleotide Microsatellite Loci From The Endangered Green Turtle (Chelonia Mydas)

We describe isolation and characterization of 20 polymorphic tetranucleotide loci from the green turtle (Chelonia mydas). We identified an average of 12.5 alleles per locus based on screening of 31 individuals foraging in the Indian River Lagoon, Florida, USA. Observed heterozygosity ranged from 0.53 to 1.00, with a mean of 0.85. This microsatellite suite has a combined non-exclusion probability of identity of 2.45 × 10-28. These markers will complement those already available for green turtles in individual-based as well as population level genetic analyses. © 2012 Springer Science+Business Media B.V