Fgf is required to regulate anterior-posterior patterning in the Xenopus lateral plate mesoderm

Given that the lateral plate mesoderm (LPM) gives rise to the cardiovascular system, identifying the cascade of signalling events that subdivides the LPM into distinct regions during development is an important question. Retinoic acid (RA) is known to be necessary for establishing the expression boundaries of important transcription factors that demarcate distinct regions along the anterior posterior axis of the LPM. Here, we demonstrate that fibroblast growth factor (Fgf) signalling is also necessary for regulating the expression domains of the same transcription factors (nkx2.5, foxf1, hand1 and sall3) by restricting the RA responsive LPM domains. When Fgf signalling is inhibited in neurula stage embryos, the more posterior LPM expression domains are lost, while the more anterior domains are extended further posterior. The domain changes are maintained throughout development as Fgf inhibition results in similar domain changes in late stage embryos. We also demonstrate that Fgf signalling is necessary for both the initiation of heart specification, and for maintaining heart specification until overt differentiation occurs. Fgf signalling is also necessary to restrict vascular patterning and create a vascular free domain in the posterior end of the LPM that correlates with the expression of hand1. Finally, we show cross talk between the RA and Fgf signalling pathways in the patterning of the LPM. We suggest that this tissue wide patterning event, active during the neurula stage, is an initial step in regional specification of the LPM, and this process is an essential early event in LPM patterning. © 2011 Elsevier Ireland Ltd

A rigorous formulation of the cosmological Newtonian limit without averaging

We prove the existence of a large class of one-parameter families of cosmological solutions to the Einstein-Euler equations that have a Newtonian limit. This class includes solutions that represent a finite, but otherwise arbitrary, number of compact fluid bodies. These solutions provide exact cosmological models that admit Newtonian limits but, are not, either implicitly or explicitly, averaged

Constraining ocean diffusivity from the 8.2 ka event

Greenland ice-core data containing the 8.2 ka event are utilized by a model-data intercomparison within the Earth system model of intermediate complexity, CLIMBER-2.3 to investigate their potential for constraining the range of uncertain ocean diffusivity properties. Within a stochastic version of the model (Bauer et al. in Paleoceanography 19:PA3014, 2004) it has been possible to mimic the pronounced cooling of the 8.2 ka event with relatively good accuracy considering the timing of the event in comparison to other modelling exercises. When statistically inferring from the 8.2 ka event on diffusivity the technical difficulty arises to establish the related likelihood numerically per realisation of the uncertain model parameters: while mainstream uncertainty analyses can assume a quasi-Gaussian shape of likelihood, with weather fluctuating around a long term mean, the 8.2 ka event as a highly nonlinear effect precludes such an a priori assumption. As a result of this study the Bayesian Analysis leads to a sharp single-mode likelihood for ocean diffusivity parameters within CLIMBER-2.3. Depending on the prior distribution this likelihood leads to a reduction of uncertainty in ocean diffusivity parameters (e. g. for flat prior uncertainty in the vertical ocean diffusivity parameter is reduced by factor 2). These results highlight the potential of paleo data to constrain uncertain system properties and strongly suggest to make further steps with more complex models and richer data sets to harvest this potential. © The Author(s) 2009

Constraining ocean diffusivity from the 8.2 ka event

Greenland ice-core data containing the 8.2 ka event are utilized by a model-data intercomparison within the Earth system model of intermediate complexity, CLIMBER-2.3 to investigate their potential for constraining the range of uncertain ocean diffusivity properties. Within a stochastic version of the model (Bauer et al. in Paleoceanography 19:PA3014, 2004) it has been possible to mimic the pronounced cooling of the 8.2 ka event with relatively good accuracy considering the timing of the event in comparison to other modelling exercises. When statistically inferring from the 8.2 ka event on diffusivity the technical difficulty arises to establish the related likelihood numerically per realisation of the uncertain model parameters: while mainstream uncertainty analyses can assume a quasi-Gaussian shape of likelihood, with weather fluctuating around a long term mean, the 8.2 ka event as a highly nonlinear effect precludes such an a priori assumption. As a result of this study the Bayesian Analysis leads to a sharp single-mode likelihood for ocean diffusivity parameters within CLIMBER-2.3. Depending on the prior distribution this likelihood leads to a reduction of uncertainty in ocean diffusivity parameters (e. g. for flat prior uncertainty in the vertical ocean diffusivity parameter is reduced by factor 2). These results highlight the potential of paleo data to constrain uncertain system properties and strongly suggest to make further steps with more complex models and richer data sets to harvest this potential. © The Author(s) 2009

Nuclear spin coherence in a quantum wire

We have observed millisecond-long coherent evolution of nuclear spins in a quantum wire at 1.2 K. Local, all-electrical manipulation of nuclear spins is achieved by dynamic nuclear polarization in the breakdown regime of the Integer Quantum Hall Effect combined with pulsed Nuclear Magnetic Resonance. The excitation thresholds for the breakdown are significantly smaller than what would be expected for our sample and the direction of the nuclear polarization can be controlled by the voltage bias. As a four-level spin system, the device is equivalent to two qubits.Comment: 5 pages, 5 figure

Development of the fisheries of the Eastern North Pacific : a natural-cultural systems perspective

The eastern margin of the Eastern North Pacific Ocean was classified into physiographic regions based on a suite of physical characteristics. Information on cultural and biological characteristics of this area was meshed with this classification. The result was a classification of the Eastern North Pacific into natural-cultural systems whose boundaries coincide with those of physiographic regions. Development of commercial fisheries was examined in three selected natural-cultural systems over a span of 88 years in order to identify developmental patterns unique to each and similar in all systems. Life history patterns of selected species were also examined within the context of characteristics of natural and cultural systems of the Eastern North Pacific. Species life history patterns have developed within, and therefore may tend to correlate with, general patterns in physical environment as they occur in different areas in the Eastern North Pacific. Yet life history patterns are also affected by cultural factors like exploitation and habitat destruction. Like life history patterns, fisheries also have developed differently in each natural-cultural system in the Eastern North Pacific due to differences in many interacting physical, cultural, and biological characteristics. Differences in fishery development between systems include management and exploitation techniques and technology, but also include characteristics of catch such as taxonomic composition and trophic composition, and distance from shore from which the majority of the catch came. Yet there were also similarities in patterns of fishery development between different natural-cultural systems. A `fishing up' process occurred in each natural-cultural system examined, along with declines in catch of most species that maintained a high value. Shifts in trophic structure of the catch occurred, with movement toward proportionally greater landing weights of species of lower trophic groups. Implications of such generalized patterns of exploitation and of fishery development for species life histories and for fish communities are discussed, and several management measures are suggested

Diagnostic, prognostic and predictive relevance of molecular markers in gliomas

The advances of genome-wide ‘discovery platforms’ and the increasing affordability of the analysis of significant sample sizes have led to the identification of novel mutations in brain tumours that became diagnostically and prognostically relevant. The development of mutation-specific antibodies has facilitated the introduction of these convenient biomarkers into most neuropathology laboratories and has changed our approach to brain tumour diagnostics. However, tissue diagnosis will remain an essential first step for the correct stratification for subsequent molecular tests, and the combined interpretation of the molecular and tissue diagnosis ideally remains with the neuropathologist. This overview will help our understanding of the pathobiology of common intrinsic brain tumours in adults and help guiding which molecular tests can supplement and refine the tissue diagnosis of the most common adult intrinsic brain tumours. This article will discuss the relevance of 1p/19q codeletions, IDH1/2 mutations, BRAF V600E and BRAF fusion mutations, more recently discovered mutations in ATRX, H3F3A, TERT, CIC and FUBP1, for diagnosis, prognostication and predictive testing. In a tumour-specific topic, the role of mitogen-activated protein kinase pathway mutations in the pathogenesis of pilocytic astrocytomas will be covered

INI1 mutations in meningiomas at a potential hotspot in exon 9

Rhabdoid tumours have been shown to carry somatic mutations in the INI1 (SMARCB1/hSNF5) gene. A considerable fraction of these tumours exhibit allelic losses on chromosome 22. Allelic loss on 22q also is characteristic for meningiomas, however most of these alterations are considered to be associated with mutations of the NF2 gene. We examined a series of 126 meningiomas for alterations in the INI1 gene. Four identical somatic mutations in exon 9 were detected resulting in an exchange of Arg to His in position 377 of INI1. Our observations were reproduced both by using DNA from a new round of extraction and by employing overlapping primers. This mutational hotspot therefore appears to be an important target in the formation of a fraction of meningiomas. In addition, 4 novel polymorphisms of INI1 were characterized. Our data indicate that the INI1 is a second tumour suppressor gene on chromosome 22 that may be important for the genesis of meningiomas. © 2001 Cancer Research Campaign http://www.bjcancer.co

Understanding early organogenesis using a simplified in situ hybridization protocol in Xenopus

Organogenesis is the study of how organs are specified and then acquire their specific shape and functions during development. The Xenopuslaevis embryo is very useful for studying organogenesis because their large size makes them very suitable for identifying organs at the earliest steps in organogenesis. At this time, the primary method used for identifying a specific organ or primordium is whole mount in situ hybridization with labeled antisense RNA probes specific to a gene that is expressed in the organ of interest. In addition, it is relatively easy to manipulate genes or signaling pathways in Xenopus and in situ hybridization allows one to then assay for changes in the presence or morphology of a target organ. Whole mount in situ hybridization is a multi-day protocol with many steps involved. Here we provide a simplified protocol with reduced numbers of steps and reagents used that works well for routine assays. In situ hybridization robots have greatly facilitated the process and we detail how and when we utilize that technology in the process. Once an in situ hybridization is complete, capturing the best image of the result can be frustrating. We provide advice on how to optimize imaging of in situ hybridization results. Although the protocol describes assessing organogenesis in Xenopus laevis, the same basic protocol can almost certainly be adapted to Xenopus tropicalis and other model systems

Dynamical elastic bodies in Newtonian gravity

Well-posedness for the initial value problem for a self-gravitating elastic body with free boundary in Newtonian gravity is proved. In the material frame, the Euler-Lagrange equation becomes, assuming suitable constitutive properties for the elastic material, a fully non-linear elliptic-hyperbolic system with boundary conditions of Neumann type. For systems of this type, the initial data must satisfy compatibility conditions in order to achieve regular solutions. Given a relaxed reference configuration and a sufficiently small Newton's constant, a neigborhood of initial data satisfying the compatibility conditions is constructed