Abnormal arterial-venous fusions and fate specification in mouse embryos lacking blood flow.

The functions of blood flow in the morphogenesis of mammalian arteries and veins are not well understood. We examined the development of the dorsal aorta (DA) and the cardinal vein (CV) in Ncx1 -/- mutants, which lack blood flow due to a deficiency in a sodium calcium ion exchanger expressed specifically in the heart. The mutant DA and CV were abnormally connected. The endothelium of the Ncx1 -/- mutant DA lacked normal expression of the arterial markers ephrin-B2 and Connexin-40. Notch1 activation, known to promote arterial specification, was decreased in mutant DA endothelial cells (ECs), which ectopically expressed the venous marker Coup-TFII. These findings suggest that flow has essential functions in the DA by promoting arterial and suppressing venous marker expression. In contrast, flow plays a lesser role in the CV, because expression of arterial-venous markers in CV ECs was not as dramatically affected in Ncx1 -/- mutants. We propose a molecular mechanism by which blood flow mediates DA and CV morphogenesis, by regulating arterial-venous specification of DA ECs to ensure proper separation of the developing DA and CV

As you like it in Gothenburg 1920 Wilhelm Stenhammar’s incidental music in interaction with play, place and pastoral concerns

As you like it in Gothenburg 1920: Wilhelm Stenhammar’s incidental music in interaction with play, place and pastoral concerns This article focuses on Wilhelm Stenhammar’s incidental music to the 1920 production of Shakespeare’s play As you like it at the Lorensbergsteatern in Gothenburg. It examines how the music relates to seminal ideas in the play, to the particular Lorensberg production, and to contemporary society. It suggests ways in which interconnected notions of place and pastoral values, grounded in understandings of the historicity of particular landscapes, might inform aesthetic expressions as well as highlight the contemporary relevance of the production, and argues that the musical voice is central to this insight. Furthermore, the article examines Stenhammar’s music in its context of being at the temporal cross-road between historical and modern values, aesthetics and ideologies, particularly those contained in pastoral values or landscape ideologies. While negotiating these concerns, Stenhammar’s music, this article suggests, embraces both particularly local issues and issues that reach out to wider contexts and times

Rare Presentation of Rosai-Dorfman Disease in Soft Tissue: Diagnostic Findings and Surgical Treatment.

Introduction and Importance. Rosai-Dorfman disease (RDD) is a rare, benign type II histiocytosis characterized by the infiltration of S100+ histiocytes and emperipolesis. The disease may present in the lymph nodes (nodal RDD), in extranodal sites, or in both nodal and extranodal sites. Among those patients who present exclusively in extranodal sites, only a minority of cases present in the soft tissue. Case Presentation. An 18-year-old female presented to orthopedic oncology clinic with a chief complaint of a mass located in her lower back. The patient underwent excision of the lumbosacral mass. Pathologic review demonstrated emperipolesis of lymphocytes and plasma cells within enlarged, eosinophilic histiocytes in a background of lymphoplasmacytic infiltration and collagenous stroma. Immunohistochemical staining demonstrated S100+ and CD163+ histiocytes, consistent with diagnosis of soft tissue RDD. Clinical Discussion. Histologically, RDD is generally characterized by emperipolesis-the presence of intact lymphocytes within the histiocyte cytoplasm-and a mixed infiltrate of S100+ histiocytes, mononuclear cells, plasma cells, and lymphocytes. Although soft tissue RDD may histologically resemble nodal RDD, soft tissue RDD also demonstrates some notable histologic differences including the lack of nodal architecture, the presence of increased fibrosis and collagen deposition, and generally fewer RDD cells. Conclusion. This case presentation demonstrates one few reports of isolated soft tissue RDD within the lumbosacral region without associated lymphadenopathy or skin changes and highlights the heterogeneity that still exists in the treatment paradigm of extranodal RDD

Measuring degree-degree association in networks

The Pearson correlation coefficient is commonly used for quantifying the global level of degree-degree association in complex networks. Here, we use a probabilistic representation of the underlying network structure for assessing the applicability of different association measures to heavy-tailed degree distributions. Theoretical arguments together with our numerical study indicate that Pearson's coefficient often depends on the size of networks with equal association structure, impeding a systematic comparison of real-world networks. In contrast, Kendall-Gibbons' $\tau_{b}$ is a considerably more robust measure of the degree-degree association

Middle Ordovician carbonate facies development, conodont biostratigraphy and faunal diversity patterns at the Lynna River, northwestern Russia

The Ordovician Period has emerged as a highly dynamic time in Earth history. Comprehensive work on chrono, chemo-and biostratigraphy has resulted in an overall wellconstrained systemic framework, but several local successions around the globe still await detailed analysis in many respects. Herein we perform a highresolution analysis of abiotic and biotic signals in the Lynna River section, a key locality in northwestern Russia. As this section has been pivotal in documenting the temporal evolution of the Great Ordovician Biodiversification Event on Baltica, the macroscopic and microscopic characteristics of the local succession reveal important paleoenvironmental information that ties into the global development during the Middle Ordovician. The results add particularly to the understanding of the characteristics and largescale sedimentary ‘behavior’ of the Baltoscandian paleobasin. Microfacies vary consistently with the macroscopic appearance of the rocks, with intervals characterized by competent limestone being associated with coarser carbonate textures and intervals dominated by marly beds associated with finer textures. Along with carbonate textures, fossil grain assemblages vary in a rhythmic (~cyclic) manner. The local rocks are commonly partly dolomitized, with the proportion of dolomitization increasing upsection. Regional comparisons suggest that the changes in overall macro and microfacies were strongly related to variations in sea level. New highresolution conodont biostratigraphic data largely confirm previous regional correlations based on lithostratigraphy and trilobite faunas, and enable more robust correlations worldwide

Investigations of a Cretaceous limestone with spectral induced polarization and scanning electron microscopy

Characterization of varying bedrock properties is a common need in various contexts, ranging from large infrastructure pre-investigations to environmental protection. A direct current resistivity and time domain induced polarization (IP) survey aiming to characterize properties of a Cretaceous limestone was carried out in the Kristianstad basin, Sweden. The time domain IP data was processed with a recently developed method in order to suppress noise from the challenging urban setting in the survey area. The processing also enabled extraction of early decay times resulting in broader spectra of the time decays and inversion for Cole-Cole parameters. The aims of this study is to investigate if large-scale geoelectrical variations as well as small-scale structural and compositional variations exist within the Kristianstad limestone, and to evaluate the usefulness of Cole-Cole inverted IP data in early time ranges for bedrock characterization. The inverted sections showed variations within the limestone that could be caused by variations in texture and composition. Samples from a deep drilling in the Kristianstad basin were investigated with scanning electron microscopy and energy dispersive X-ray spectroscopy, and the results showed that varying amounts of pyrite, glauconite and clay matrix were present at different levels in the limestone. The local high IP anomalies in the limestone could be caused by these minerals otherwise the IP responses were generally weak. There were also differences in the texture of the limestone at different levels, governed by fossil shapes and composition, proportions of calcareous cement and matrix as well as amount of silicate grains. Textural variations may have implications on the variation in Cole-Cole relaxation time and frequency factor. However, more research is needed in order to directly connect microgeometrical properties in limestone to spectral IP responses. The results from this study show that it is possible to recover useable spectral information from early decay times. We also show that under certain conditions (e.g. relatively short relaxation times in the subsurface), it is possible to extract spectral information from time domain IP data measured with on-off times as short as 1 s

Transient Calcium and Dopamine Increase PKA Activity and DARPP-32 Phosphorylation

Reinforcement learning theorizes that strengthening of synaptic connections in medium spiny neurons of the striatum occurs when glutamatergic input (from cortex) and dopaminergic input (from substantia nigra) are received simultaneously. Subsequent to learning, medium spiny neurons with strengthened synapses are more likely to fire in response to cortical input alone. This synaptic plasticity is produced by phosphorylation of AMPA receptors, caused by phosphorylation of various signalling molecules. A key signalling molecule is the phosphoprotein DARPP-32, highly expressed in striatal medium spiny neurons. DARPP-32 is regulated by several neurotransmitters through a complex network of intracellular signalling pathways involving cAMP (increased through dopamine stimulation) and calcium (increased through glutamate stimulation). Since DARPP-32 controls several kinases and phosphatases involved in striatal synaptic plasticity, understanding the interactions between cAMP and calcium, in particular the effect of transient stimuli on DARPP-32 phosphorylation, has major implications for understanding reinforcement learning. We developed a computer model of the biochemical reaction pathways involved in the phosphorylation of DARPP-32 on Thr34 and Thr75. Ordinary differential equations describing the biochemical reactions were implemented in a single compartment model using the software XPPAUT. Reaction rate constants were obtained from the biochemical literature. The first set of simulations using sustained elevations of dopamine and calcium produced phosphorylation levels of DARPP-32 similar to that measured experimentally, thereby validating the model. The second set of simulations, using the validated model, showed that transient dopamine elevations increased the phosphorylation of Thr34 as expected, but transient calcium elevations also increased the phosphorylation of Thr34, contrary to what is believed. When transient calcium and dopamine stimuli were paired, PKA activation and Thr34 phosphorylation increased compared with dopamine alone. This result, which is robust to variation in model parameters, supports reinforcement learning theories in which activity-dependent long-term synaptic plasticity requires paired glutamate and dopamine inputs