Activation of Aurora-A Kinase by Protein Partner Binding and Phosphorylation Are Independent and Synergistic

Protein kinases are activated by phosphorylation and by the binding of activator proteins. The interplay of these two factors is incompletely understood. We applied energetic analysis to this question and characterized the activation process of the serine/threonine kinase Aurora-A by phosphorylation and by its protein partner, targeting protein for Xenopus kinesin-like protein 2 (TPX2). We discovered that these two activators act synergistically and without a predefined order: each can individually increase the activity of Aurora-A, and the effect of both bound together is the exact sum of their individual contributions to catalysis. Unexpectedly, the unphosphorylated enzyme has catalytic activity that is increased 15-fold by the binding of TPX2 alone. The energetic contribution of phosphorylation to catalysis is 2-fold greater than that of TPX2 binding, which is independent of the phosphorylation state of the enzyme. Based on this analysis, we propose a revised, fluid model of Aurora-A activation in which the first step is a reduction in the mobility of the activation loop by either TPX2 binding or phosphorylation. Furthermore, our results suggest that unphosphorylated Aurora-A bound to the mitotic spindle by TPX2 is catalytically active and that the phosphorylation state of Aurora-A is an inaccurate surrogate for its activity. Extending this form of analysis will allow us to compare quantitatively the effects of the whole network of kinase-activating partners. Comparison with other kinases showed that kinetic characterization detects those kinases whose activation loops undergo a rearrangement upon phosphorylation and thus whose unphosphorylated state offers a distinct target for the development of Type II inhibitors

‘Nedoceratops’: An Example of a Transitional Morphology

Background: The holotype and only specimen of the chasmosaurine ceratopsid dinosaur ‘Nedoceratops hatcheri ’ has been the source of considerable taxonomic debate since its initial description. At times it has been referred to its own genus while at others it has been considered synonymous with the contemporaneous chasmosaurine Triceratops. Most recently, the debate has focused on whether the specimen represents an intermediate ontogenetic stage between typical young adult Triceratops and the proposed mature morphology, which was previously considered to represent a distinct genus, ‘Torosaurus’. Methodology/Principal Findings: The only specimen of ‘Nedoceratops hatcheri ’ was examined and the proposed diagnostic features of this taxon were compared with other chasmosaurine ceratopsids. Every suggested autapomorphy of ‘Nedoceratops ’ is found in specimens of Triceratops. In this study, Triceratops includes the adult ‘Torosaurus ’ morphology. The small parietal fenestra and elongate squamosals of Nedoceratops are consistent with a transition from a short, solid parietalsquamosal frill to an expanded, fenestrated condition. Objections to this hypothesis regarding the number of epiossifications of the frill and alternations of bone surface texture were explored through a combination of comparative osteology and osteohistology. The synonymy of the three taxa was further supported by these investigations. Conclusions/Significance: The Triceratops, ‘Torosaurus’, and ‘Nedoceratops ’ morphologies represent ontogenetic variatio

PocketMatch: A new algorithm to compare binding sites in protein structures

Background: Recognizing similarities and deriving relationships among protein molecules is a fundamental
requirement in present-day biology. Similarities can be present at various levels which can be detected through comparison of protein sequences or their structural folds. In some cases similarities obscure at these levels could be present merely in the substructures at their binding sites. Inferring functional similarities between protein molecules by comparing their binding sites is still largely exploratory and not as yet a routine protocol. One of
the main reasons for this is the limitation in the choice of appropriate analytical tools that can compare binding sites with high sensitivity. To benefit from the enormous amount of structural data that is being rapidly accumulated, it is essential to have high throughput tools that enable large scale binding site comparison.

Results: Here we present a new algorithm PocketMatch for comparison of binding sites in a frame invariant
manner. Each binding site is represented by 90 lists of sorted distances capturing shape and chemical nature of the site. The sorted arrays are then aligned using an incremental alignment method and scored to obtain PMScores for pairs of sites. A comprehensive sensitivity analysis and an extensive validation of the algorithm have been carried out. Perturbation studies where the geometry of a given site was retained but the residue types were changed randomly, indicated that chance similarities were virtually non-existent. Our analysis also demonstrates that shape information alone is insufficient to discriminate between diverse binding sites, unless
combined with chemical nature of amino acids.

Conclusions: A new algorithm has been developed to compare binding sites in accurate, efficient and
high-throughput manner. Though the representation used is conceptually simplistic, we demonstrate that along
with the new alignment strategy used, it is sufficient to enable binding comparison with high sensitivity. Novel methodology has also been presented for validating the algorithm for accuracy and sensitivity with respect to geometry and chemical nature of the site. The method is also fast and takes about 1/250th second for one comparison on a single processor. A parallel version on BlueGene has also been implemented

Anatomy and Taxonomic Status of the Chasmosaurine Ceratopsid Nedoceratops hatcheri from the Upper Cretaceous Lance Formation of Wyoming, U.S.A

Background: The validity of Nedoceratops hatcheri, a chasmosaurine ceratopsid dinosaur known from a single skull recovered in the Lance Formation of eastern Wyoming, U.S.A., has been debated for over a century. Some have argued that the taxon is an aberrant Triceratops, and most recently it was proposed that N. hatcheri represents an intermediate ontogenetic stage between ‘‘young adult’ ’ and ‘‘old adult’ ’ forms of a single taxon previously split into Triceratops and Torosaurus. Methodology/Principal Findings: The holotype skull of Nedoceratops hatcheri was reexamined in order to map reconstructed areas and compare the specimen with other ceratopsids. Although squamosal fenestrae are almost certainly not of taxonomic significance, some other features are unique to N. hatcheri. These include a nasal lacking a recognizable horn, nearly vertical postorbital horncores, and relatively small parietal fenestrae. Thus, N. hatcheri is tentatively considered valid, and closely related to Triceratops spp. The holotype of N. hatcheri probably represents an ‘‘old adult,’ ’ based upon bone surface texture and the shape of the horns and epiossifications on the frill. In this study, Torosaurus is maintained as a genus distinct from Triceratops and Nedoceratops. Synonymy of the three genera as ontogenetic stages of a single taxon would require cranial changes otherwise unknown in ceratopsids, including additions of ossifications to the frill and repeated alternation of bone surface texture between juvenile and adult morphotypes

Torosaurus Is Not Triceratops: Ontogeny in Chasmosaurine Ceratopsids as a Case Study in Dinosaur Taxonomy

Background: In horned dinosaurs, taxonomy is complicated by the fact that the cranial ornament that distinguishes species changes with age. Based on this observation, it has been proposed that the genera Triceratops and Torosaurus are in fact synonymous, with specimens identified as Torosaurus representing the adult form of Triceratops. The hypothesis of synonymy makes three testable predictions: 1) the species in question should have similar geographic and stratigraphic distributions, 2) specimens assigned to Torosaurus should be more mature than those assigned to Triceratops, and 3) intermediates should exist that combine features of Triceratops and Torosaurus. The first condition appears to be met, but it remains unclear whether the other predictions are borne out by the fossil evidence. Methodology/Principal Findings: We assessed the relative maturity of Torosaurus and Triceratops specimens by coding skulls for characters that vary with maturity, and then using a clustering analysis to arrange them into a growth series. We found that a well-defined sequence of changes exists in horned dinosaurs: development of cranial ornament occurs in juveniles, followed by fusion of the skull roof in subadults, and finally, the epoccipitals, epijugals, and rostral fuse to the skull in adults. Using this scheme, we identified mature and immature individuals of both Torosaurus and Triceratops. Furthermore, we describe the ventral depressions on the frill of Triceratops, and show that they differ in shape and position from the parietal fenestrae of Torosaurus. Thus, we conclude that these structures are not intermediates between the soli

A New Eusuchian Crocodyliform with Novel Cranial Integument and Its Significance for the Origin and Evolution of Crocodylia

Crocodyliforms were one of the most successful groups of Mesozoic tetrapods, radiating into terrestrial, semiaquatic and marine environments, while occupying numerous trophic niches, including carnivorous, insectivorous, herbivorous, and piscivorous species. Among these taxa were the enigmatic, poorly represented flat-headed crocodyliforms from the late Cretaceous of northern Africa. Here we report a new, giant crocodyliform from the early Late Cretaceous (Cenomanian) Kem Kem Formation of Morocco. Represented by a partial braincase, the taxon has an extremely long, flat skull with large jaw and craniocervical muscles. The skull roof is ridged and ornamented with a broad, rough boss surrounded by significant vascular impressions, likely forming an integumentary structure unique among crocodyliforms. Size estimates using endocranial volume indicate the specimen was very large. The taxon possesses robust laterosphenoids with laterally oriented capitate processes and isolated epipterygoids, features allying it with derived eusuchians. Phylogenetic analysis finds the taxon to be a derived eusuchian and sister taxon to Aegyptosuchus, a poorly understood, early Late Cretaceous taxon from the Bahariya formation. This clade forms the sister clade of crown-group Crocodylia, making these taxa the earliest eusuchian crocodyliforms known from Africa. These results shift phylogenetic and biogeographical hypotheses on the origin of modern crocodylians towards the circum-Tethyean region and provide important new data on eusuchian morphology and evolution

Community-based management induces rapid recovery of a high-value tropical freshwater fishery

Tropical wetlands are highly threatened socio-ecological systems, where local communities rely heavily on aquatic animal protein, such as fish, to meet food security. Here, we quantify how a ‘win-win’ community-based resource management program induced stock recovery of the world’s largest scaled freshwater fish (Arapaima gigas), providing both food and income. We analyzed stock assessment data over eight years and examined the effects of protected areas, community-based management, and landscape and limnological variables across 83 oxbow lakes monitored along a ~500-km section of the Juruá River of Western Brazilian Amazonia. Patterns of community management explained 71.8% of the variation in arapaima population sizes. Annual population counts showed that protected lakes on average contained 304.8 (±332.5) arapaimas, compared to only 9.2 (±9.8) in open-access lakes. Protected lakes have become analogous to a high-interest savings account, ensuring an average annual revenue of US$10,601 per community and US$1046.6 per household, greatly improving socioeconomic welfare. Arapaima management is a superb window of opportunity in harmonizing the co-delivery of sustainable resource management and poverty alleviation. We show that arapaima management deserves greater attention from policy makers across Amazonian countries, and highlight the need to include local stakeholders in conservation planning of Amazonian floodplains

New Horned Dinosaurs from Utah Provide Evidence for Intracontinental Dinosaur Endemism

Background:\ud During much of the Late Cretaceous, a shallow, epeiric sea divided North America into eastern and western landmasses. The western landmass, known as Laramidia, although diminutive in size, witnessed a major evolutionary radiation of dinosaurs. Other than hadrosaurs (duck-billed dinosaurs), the most common dinosaurs were ceratopsids (large-bodied horned dinosaurs), currently known only from Laramidia and Asia. Remarkably, previous studies have postulated the occurrence of latitudinally arrayed dinosaur “provinces,” or “biomes,” on Laramidia. Yet this hypothesis has been challenged on multiple fronts and has remained poorly tested.\ud \ud Methodology/Principal Findings:\ud Here we describe two new, co-occurring ceratopsids from the Upper Cretaceous Kaiparowits Formation of Utah that provide the strongest support to date for the dinosaur provincialism hypothesis. Both pertain to the clade of ceratopsids known as Chasmosaurinae, dramatically increasing representation of this group from the southern portion of the Western Interior Basin of North America. Utahceratops gettyi gen. et sp. nov.—characterized by short, rounded, laterally projecting supraorbital horncores and an elongate frill with a deep median embayment—is recovered as the sister taxon to Pentaceratops sternbergii from the late Campanian of New Mexico. Kosmoceratops richardsoni gen. et sp. nov.—characterized by elongate, laterally projecting supraorbital horncores and a short, broad frill adorned with ten well developed hooks—has the most ornate skull of any known dinosaur and is closely allied to Chasmosaurus irvinensis from the late Campanian of Alberta.\ud \ud Conclusions/Significance:\ud Considered in unison, the phylogenetic, stratigraphic, and biogeographic evidence documents distinct, co-occurring chasmosaurine taxa north and south on the diminutive landmass of Laramidia. The famous Triceratops and all other, more nested chasmosaurines are postulated as descendants of forms previously restricted to the southern portion of Laramidia. Results further suggest the presence of latitudinally arrayed evolutionary centers of endemism within chasmosaurine ceratopsids during the late Campanian, the first documented occurrence of intracontinental endemism within dinosaurs

The nucleoporin ALADIN regulates Aurora A localization to ensure robust mitotic spindle formation

The formation of the mitotic spindle is a complex process that requires massive cellular reorganization. Regulation by mitotic kinases controls this entire process. One of these mitotic controllers is Aurora A kinase, which is itself highly regulated. In this study, we show that the nuclear pore protein ALADIN is a novel spatial regulator of Aurora A. Without ALADIN, Aurora A spreads from centrosomes onto spindle microtubules, which affects the distribution of a subset of microtubule regulators and slows spindle assembly and chromosome alignment. ALADIN interacts with inactive Aurora A and is recruited to the spindle pole after Aurora A inhibition. Of interest, mutations in ALADIN cause triple A syndrome. We find that some of the mitotic phenotypes that we observe after ALADIN depletion also occur in cells from triple A syndrome patients, which raises the possibility that mitotic errors may underlie part of the etiology of this syndrome

Gravitational waves from single neutron stars: an advanced detector era survey

With the doors beginning to swing open on the new gravitational wave astronomy, this review provides an up-to-date survey of the most important physical mechanisms that could lead to emission of potentially detectable gravitational radiation from isolated and accreting neutron stars. In particular we discuss the gravitational wave-driven instability and asteroseismology formalism of the f- and r-modes, the different ways that a neutron star could form and sustain a non-axisymmetric quadrupolar "mountain" deformation, the excitation of oscillations during magnetar flares and the possible gravitational wave signature of pulsar glitches. We focus on progress made in the recent years in each topic, make a fresh assessment of the gravitational wave detectability of each mechanism and, finally, highlight key problems and desiderata for future work.Comment: 39 pages, 12 figures, 2 tables. Chapter of the book "Physics and Astrophysics of Neutron Stars", NewCompStar COST Action 1304. Minor corrections to match published versio