Solar cycle variation in solar f-mode frequencies and radius

Using data from the Global Oscillation Network Group (GONG) covering the period from 1995 to 1998, we study the change with solar activity in solar f-mode frequencies. The results are compared with similar changes detected from the Michelson Doppler Imager (MDI) data. We find variations in f-mode frequencies which are correlated with solar activity indices. If these changes are due to variation in solar radius then the implications are that the solar radius decreases by about 5 km from minimum to maximum activity.Comment: To appear in Solar Physic

Analyse der Tätigkeiten kardiovaskulärer Gewebebanken in Deutschland in den Jahren 2007 bis 2010

__Background:__ Especially in complicated aortic valve endocarditis, infections of the aorta by mycotic aortic aneurysms and prosthetic infections, or as part of the Ross procedure, the use of allogeneic heart valve transplants remains important. The production of such allografts in Germany is the task of cardiovascular tissue banks (CVTB). __Materials and methods:__ During an analysis of the years 2007-2010, basic data on donor numbers, production, and distribution as well as the technical conditions of not only the four participating CVTB (Bad Oeynhausen, Berlin, Kiel, Munich) but also data from the CVTB Rotterdam as an external reference were recorded. __Results:__ The German CVTB delivered an average of 44 aortic and 95 pulmonary allografts per year to clinical users. By incorporating the annually imported valve allografts, the demand in Germany approximately averages 220 heart valve allografts per year. The heart tissue was harvested from approximately 100 multiorgan donors, 45 cardiovascular deaths, and 80 domino donors annually. __Discussion:__ The participating cardiovascular tissue banks have comparable technical and administrative requirements and are able to produce tissue preparations according to the rules of Good Professional Practice in accordance with § 3 (3) AMWHV to assess their quality, whereby harmonization of microbiological monitoring and antibiotic treatment is still necessary

Kwashiorkor: A Prospective Ten-Year Follow-up Study

The physical status of 123 cases of kwashiorkor, followed up longitudinally for 10 years, was analysed. Their status was compared with that of 97 control siblings who had never suffered from kwashiorkor, but who had grown up under the same environmental conditions as the expatients. It was found that 10 years after the episode of kwashiorkor about half of the children had reached international growth standards in weight and height, thus demonstrating the capacity for complete physical recovery. No significant anthropometric or biochemical differences were found between ex-patients and control siblings at the 10-year follow-up examination. This is adequate proof that the episode of kwashiorkor per se cannot be held responsible for the growth retardation that occurred in some of the children. The children who were most severely retarded in weight and height on admission tended to remain the most severely retarded in growth after 10 years. The children who were the oldest on admission were more retarded in weight after 10 years than the children who were admitted at a younger age. Although these facts may imply that the severity and possibly the duration of the malnutrition episode adversely affected subsequent physical growth, a high current incidence of hypoalbuminaemia was found in both ex-patients and control siblings, indicating continuing malnutrition, the effects of which cannot be separated from possible deleterious effects of thil original malnutrition episode. Linear growth also correlated significantly with midparental height and a complex of adverse social circumstances.Failure to attain international growth standards in some of the children was therefore apparently due to a combination of factors and at present it is impossible to distinguish any single one of these as being more important than the others. Since about half of the children did reach adequate growth standards despite their poor living conditions, it is clearly worth while to treat every case of malnutrition. At the same time public health supervision and preventative social measures should be greatly increased to protect the child population throughout the growing period. S. Afr. Med. J., 45, 1427 (1971

Under pressure: Response urgency modulates striatal and insula activity during decision-making under risk

When deciding whether to bet in situations that involve potential monetary loss or gain (mixed gambles), a subjective sense of pressure can influence the evaluation of the expected utility associated with each choice option. Here, we explored how gambling decisions, their psychophysiological and neural counterparts are modulated by an induced sense of urgency to respond. Urgency influenced decision times and evoked heart rate responses, interacting with the expected value of each gamble. Using functional MRI, we observed that this interaction was associated with changes in the activity of the striatum, a critical region for both reward and choice selection, and within the insula, a region implicated as the substrate of affective feelings arising from interoceptive signals which influence motivational behavior. Our findings bridge current psychophysiological and neurobiological models of value representation and action-programming, identifying the striatum and insular cortex as the key substrates of decision-making under risk and urgency

Neurodegeneration and Epilepsy in a Zebrafish Model of CLN3 Disease (Batten Disease)

The neuronal ceroid lipofuscinoses are a group of lysosomal storage disorders that comprise the most common, genetically heterogeneous, fatal neurodegenerative disorders of children. They are characterised by childhood onset, visual failure, epileptic seizures, psychomotor retardation and dementia. CLN3 disease, also known as Batten disease, is caused by autosomal recessive mutations in the CLN3 gene, 80–85% of which are a ~1 kb deletion. Currently no treatments exist, and after much suffering, the disease inevitably results in premature death. The aim of this study was to generate a zebrafish model of CLN3 disease using antisense morpholino injection, and characterise the pathological and functional consequences of Cln3 deficiency, thereby providing a tool for future drug discovery. The model was shown to faithfully recapitulate the pathological signs of CLN3 disease, including reduced survival, neuronal loss, retinopathy, axonopathy, loss of motor function, lysosomal storage of subunit c of mitochondrial ATP synthase, and epileptic seizures, albeit with an earlier onset and faster progression than the human disease. Our study provides proof of principle that the advantages of the zebrafish over other model systems can be utilised to further our understanding of the pathogenesis of CLN3 disease and accelerate drug discovery

On the dynamics of the adenylate energy system: homeorhesis vs homeostasis.

Biochemical energy is the fundamental element that maintains both the adequate turnover of the biomolecular structures and the functional metabolic viability of unicellular organisms. The levels of ATP, ADP and AMP reflect roughly the energetic status of the cell, and a precise ratio relating them was proposed by Atkinson as the adenylate energy charge (AEC). Under growth-phase conditions, cells maintain the AEC within narrow physiological values, despite extremely large fluctuations in the adenine nucleotides concentration. Intensive experimental studies have shown that these AEC values are preserved in a wide variety of organisms, both eukaryotes and prokaryotes. Here, to understand some of the functional elements involved in the cellular energy status, we present a computational model conformed by some key essential parts of the adenylate energy system. Specifically, we have considered (I) the main synthesis process of ATP from ADP, (II) the main catalyzed phosphotransfer reaction for interconversion of ATP, ADP and AMP, (III) the enzymatic hydrolysis of ATP yielding ADP, and (IV) the enzymatic hydrolysis of ATP providing AMP. This leads to a dynamic metabolic model (with the form of a delayed differential system) in which the enzymatic rate equations and all the physiological kinetic parameters have been explicitly considered and experimentally tested in vitro. Our central hypothesis is that cells are characterized by changing energy dynamics (homeorhesis). The results show that the AEC presents stable transitions between steady states and periodic oscillations and, in agreement with experimental data these oscillations range within the narrow AEC window. Furthermore, the model shows sustained oscillations in the Gibbs free energy and in the total nucleotide pool. The present study provides a step forward towards the understanding of the fundamental principles and quantitative laws governing the adenylate energy system, which is a fundamental element for unveiling the dynamics of cellular life

Room temperature coherent control of coupled single spins in solid

Coherent coupling between single quantum objects is at the heart of modern quantum physics. When coupling is strong enough to prevail over decoherence, it can be used for the engineering of correlated quantum states. Especially for solid-state systems, control of quantum correlations has attracted widespread attention because of applications in quantum computing. Such coherent coupling has been demonstrated in a variety of systems at low temperature1, 2. Of all quantum systems, spins are potentially the most important, because they offer very long phase memories, sometimes even at room temperature. Although precise control of spins is well established in conventional magnetic resonance3, 4, existing techniques usually do not allow the readout of single spins because of limited sensitivity. In this paper, we explore dipolar magnetic coupling between two single defects in diamond (nitrogen-vacancy and nitrogen) using optical readout of the single nitrogen-vacancy spin states. Long phase memory combined with a defect separation of a few lattice spacings allow us to explore the strong magnetic coupling regime. As the two-defect system was well-isolated from other defects, the long phase memory times of the single spins was not diminished, despite the fact that dipolar interactions are usually seen as undesirable sources of decoherence. A coherent superposition of spin pair quantum states was achieved. The dipolar coupling was used to transfer spin polarisation from a nitrogen-vacancy centre spin to a nitrogen spin, with optical pumping of a nitrogen-vacancy centre leading to efficient initialisation. At the level anticrossing efficient nuclear spin polarisation was achieved. Our results demonstrate an important step towards controlled spin coupling and multi-particle entanglement in the solid state

E3 Ligase Activity of XIAP RING Domain Is Required for XIAP-Mediated Cancer Cell Migration, but Not for Its RhoGDI Binding Activity

Although an increased expression level of XIAP is associated with cancer cell metastasis, the underlying molecular mechanisms remain largely unexplored. To verify the specific structural basis of XIAP for regulation of cancer cell migration, we introduced different XIAP domains into XIAP−/− HCT116 cells, and found that reconstitutive expression of full length HA-XIAP and HA-XIAP ΔBIR, both of which have intact RING domain, restored β-Actin expression, actin polymerization and cancer cell motility. Whereas introduction of HA-XIAP ΔRING or H467A mutant, which abolished its E3 ligase function, did not show obvious restoration, demonstrating that E3 ligase activity of XIAP RING domain played a crucial role of XIAP in regulation of cancer cell motility. Moreover, RING domain rather than BIR domain was required for interaction with RhoGDI independent on its E3 ligase activity. To sum up, our present studies found that role of XIAP in regulating cellular motility was uncoupled from its caspase-inhibitory properties, but related to physical interaction between RhoGDI and its RING domain. Although E3 ligase activity of RING domain contributed to cell migration, it was not involved in RhoGDI binding nor its ubiquitinational modification

Tubulin Tyrosination Is Required for the Proper Organization and Pathfinding of the Growth Cone

International audienceBACKGROUND: During development, neuronal growth cones integrate diffusible and contact guidance cues that are conveyed to both actin and microtubule (MT) cytoskeletons and ensure axon outgrowth and pathfinding. Although several post-translational modifications of tubulin have been identified and despite their strong conservation among species, their physiological roles during development, especially in the nervous sytem, are still poorly understood. METHODOLOGY/FINDINGS: Here, we have dissected the role of a post-translational modification of the last amino acid of the alpha-tubulin on axonal growth by analyzing the phenotype of precerebellar neurons in Tubulin tyrosin ligase knock-out mice (TTL(-/-)) through in vivo, ex vivo and in vitro analyses. TTL(-/-) neurons are devoid of tyrosinated tubulin. Their pathway shows defects in vivo, ex vivo, in hindbrains open-book preparations or in vitro, in a collagen matrix. Their axons still orient toward tropic cues, but they emit supernumerary branches and their growth cones are enlarged and exhibit an emission of mis-oriented filopodia. Further analysis of the TTL(-/-) growth cone intracellular organization also reveals that the respective localization of actin and MT filaments is disturbed, with a decrease in the distal accumulation of Myosin IIB, as well as a concomitant Rac1 over-activation in the hindbrain. Pharmacological inhibition of Rac1 over-activation in TTL(-/-) neurons can rescue Myosin IIB localization. CONCLUSIONS/SIGNIFICANCE: In the growth cone, we propose that tubulin tyrosination takes part in the relative arrangement of actin and MT cytoskeletons, in the regulation of small GTPases activity, and consequently, in the proper morphogenesis, organization and pathfinding of the growth cone during development

Saliva Proteins of Vector Culicoides Modify Structure and Infectivity of Bluetongue Virus Particles

Bluetongue virus (BTV) and epizootic haemorrhagic disease virus (EHDV) are related orbiviruses, transmitted between their ruminant hosts primarily by certain haematophagous midge vectors (Culicoides spp.). The larger of the BTV outer-capsid proteins, ‘VP2’, can be cleaved by proteases (including trypsin or chymotrypsin), forming infectious subviral particles (ISVP) which have enhanced infectivity for adult Culicoides, or KC cells (a cell-line derived from C. sonorensis). We demonstrate that VP2 present on purified virus particles from 3 different BTV strains can also be cleaved by treatment with saliva from adult Culicoides. The saliva proteins from C. sonorensis (a competent BTV vector), cleaved BTV-VP2 more efficiently than those from C. nubeculosus (a less competent / non-vector species). Electrophoresis and mass spectrometry identified a trypsin-like protease in C. sonorensis saliva, which was significantly reduced or absent from C. nubeculosus saliva. Incubating purified BTV-1 with C. sonorensis saliva proteins also increased their infectivity for KC cells ∼10 fold, while infectivity for BHK cells was reduced by 2–6 fold. Treatment of an ‘eastern’ strain of EHDV-2 with saliva proteins of either C. sonorensis or C. nubeculosus cleaved VP2, but a ‘western’ strain of EHDV-2 remained unmodified. These results indicate that temperature, strain of virus and protein composition of Culicoides saliva (particularly its protease content which is dependent upon vector species), can all play a significant role in the efficiency of VP2 cleavage, influencing virus infectivity. Saliva of several other arthropod species has previously been shown to increase transmission, infectivity and virulence of certain arboviruses, by modulating and/or suppressing the mammalian immune response. The findings presented here, however, demonstrate a novel mechanism by which proteases in Culicoides saliva can also directly modify the orbivirus particle structure, leading to increased infectivity specifically for Culicoides cells and, in turn, efficiency of transmission to the insect vector