Geometrical vortex lattice pinning and melting in YBaCuO submicron bridges.

Since the discovery of high-temperature superconductors (HTSs), most efforts of researchers have been focused on the fabrication of superconducting devices capable of immobilizing vortices, hence of operating at enhanced temperatures and magnetic fields. Recent findings that geometric restrictions may induce self-arresting hypervortices recovering the dissipation-free state at high fields and temperatures made superconducting strips a mainstream of superconductivity studies. Here we report on the geometrical melting of the vortex lattice in a wide YBCO submicron bridge preceded by magnetoresistance (MR) oscillations fingerprinting the underlying regular vortex structure. Combined magnetoresistance measurements and numerical simulations unambiguously relate the resistance oscillations to the penetration of vortex rows with intermediate geometrical pinning and uncover the details of geometrical melting. Our findings offer a reliable and reproducible pathway for controlling vortices in geometrically restricted nanodevices and introduce a novel technique of geometrical spectroscopy, inferring detailed information of the structure of the vortex system through a combined use of MR curves and large-scale simulations.

Large spin-orbit coupling and helical spin textures in 2D heterostructure [Pb2BiS3][AuTe2].

Two-dimensional heterostructures with strong spin-orbit coupling have direct relevance to topological quantum materials and potential applications in spin-orbitronics. In this work, we report on novel quantum phenomena in [Pb2BiS3][AuTe2], a new 2D strong spin-orbit coupling heterostructure system. Transport measurements reveal the spin-related carrier scattering is at odds with the Abrikosov-Gorkov model due to strong spin-orbit coupling. This is consistent with our band structure calculations which reveal a large spin-orbit coupling gap of εso = 0.21 eV. The band structure is also characterized by helical-like spin textures which are mainly induced by strong spin-orbit coupling and the inversion symmetry breaking in the heterostructure system.

Do white matter hyperintensities mediate the association between brain iron deposition and cognitive abilities in older people?

BACKGROUND AND PURPOSE: Several studies have reported associations between brain iron deposits (IDs), white matter hyperintensities (WMHs) and cognitive ability in older individuals. Whether the association between brain IDs and cognitive abilities in older people is mediated by or independent of total brain tissue damage represented by WMHs visible on structural magnetic resonance imaging (MRI) was examined. METHODS: Data from 676 community-dwelling individuals from the Lothian Birth Cohort 1936, with Mini-Mental State Examination scores >24, who underwent detailed cognitive testing and multimodal brain MRI at mean age 72.7 years were analysed. Brain IDs were assessed automatically following manual editing. WMHs were assessed semi-automatically. Brain microbleeds were visually counted. Structural equation modelling was used to test for mediation. RESULTS: Overall, 72.8% of the sample had IDs with a median total volume of 0.040 ml (i.e. 0.004% of the total brain volume). The total volume of IDs, significantly and negatively associated with general cognitive function (standardized ß = -0.17, P < 0.01), was significantly and positively associated with WMH volume (std ß = 0.13, P = 0.03). WMH volume had a significant negative association with general cognitive function, independent of IDs (std ß = -0.13, P < 0.01). The association between cognition and IDs in the brain stem (and minimally the total brain iron load) was partially and significantly mediated by WMH volume (P = 0.03). CONCLUSIONS: The negative association between brain IDs and cognitive ability in the elderly is partially mediated by WMHs, with this mediation mainly arising from the iron deposition load in the brain stem. IDs might be an indicator of small vessel disease that predisposes to white matter damage, affecting the neuronal networks underlying higher cognitive functioning.

Exploratory analysis of dietary intake and brain iron accumulation detected using magnetic resonance imaging in older individuals: the Lothian Birth Cohort 1936.

CONTEXT: Brain Iron Deposits (IDs) are associated with neurodegenerative diseases and impaired cognitive function in later life, but their cause is unknown. Animal studies have found evidence of relationships between dietary iron, calorie and cholesterol intake and brain iron accumulation. OBJECTIVES: To investigate the relationship between iron, calorie, and cholesterol intake, blood indicators of iron status, and brain IDs in humans. DESIGN, SETTING AND PARTICIPANTS: Cohort of 1063 community-dwelling older individuals born in 1936 (mean age 72.7years, SD=0.7) with dietary information, results from blood sample analyses and brain imaging data contemporaneously in old age. MEASUREMENTS: Magnetic Resonance Imaging was used to assess regional volumes of brain IDs in basal ganglia, brainstem, white matter, thalamus, and cortex/border with the corticomedullary junction, using a fully automatic assessment procedure followed by individual checking/correction where necessary. Haemoglobin, red cell count, haematocrit, mean cell volume, ferritin and transferrin were obtained from blood samples and typical daily intake of iron, calories, and cholesterol were calculated from a validated food-frequency questionnaire. RESULTS: Overall, 72.8% of the sample that had valid MRI (n=676) had brain IDs. The median total volume of IDs was 40mm3, inter-quartile range (IQR)=196. Basal ganglia IDs (median=35, IQR=159.5 mm3), were found in 70.6% of the sample. IDs in the brainstem were found in 12.9% of the sample, in the cortex in 1.9%, in the white matter in 6.1% and in the thalamus in 1.0%. The median daily intake of calories was 1808.5kcal (IQR=738.5), of cholesterol was 258.5mg (IQR=126.2) and of total iron was 11.7mg (IQR=5). Iron, calorie or cholesterol intake were not directly associated with brain IDs. However, caloric intake was associated with ferritin, an iron storage protein (p=0.01). CONCLUSION: Our results suggest that overall caloric, iron and cholesterol intake are not associated with IDs in brains of healthy older individuals but caloric intake could be associated with iron storage. Further work is required to corroborate our findings on other samples and investigate the underlying mechanisms of brain iron accumulation.

Interplay of charge and heat transport in a nano-junction in the out-of-equilibrium cotunneling regime.

We study the charge transport and heat transfer through a nano-junction composed of a small metallic grain weakly coupled to two metallic leads. We focus on the cotunneling regime out-of-equilibrium, where the bias voltage and the temperature gradient between the leads strongly drive electron and phonon degrees of freedom in the grain, which in turn have a strong feedback on the transport through the grain. We derive and solve the heat balance equation for electron and phonon degrees of freedom in the grain and self-consistently find the current-voltage characteristics. We demonstrate that the transport in the nano-junction is very sensitive to the spectrum of the bosonic modes in the grain.

Pulmonary outflow tract obstruction in fetuses with complex congenital heart disease: predicting the need for neonatal intervention.

OBJECTIVE: To identify prenatal echocardiographic markers that could predict the need for neonatal intervention in fetuses with right ventricular outflow tract obstruction. METHODS: This was a retrospective study of 52 fetuses with right ventricular outflow tract obstruction. Echocardiograms were evaluated for fetuses with either two-ventricle anatomy with a large ventricular septal defect or single-ventricle anatomy. Fetuses with pulmonary atresia were excluded. Parameters were compared between groups that did and did not require an intervention at age < 30 days. RESULTS: Fifty-two fetuses were studied; 20 (38%) underwent neonatal intervention and 32 (62%) did not. The most common diagnosis was tetralogy of Fallot (n = 32). Fetuses with two ventricles that required an intervention had lower pulmonary valve diameter Z-score (PV-Z-score) (-4.8 ± 2.1 vs. -2.6 ± 1.1; P = 0.0002) and lower pulmonary valve to aortic valve annular diameter ratio (PV/AoV) (0.53 ± 0.15 vs. 0.66 ± 0.1; P = 0.003). Using a PV/AoV ratio of < 0.6 or a PV-Z-score of < -3 at final echocardiographic examination was highly sensitive (92%) but poorly specific (50%), whereas classifying direction of flow in the ductus arteriosus as either normal (all pulmonary-to-aorta) or abnormal (aorta-to-pulmonary or bidirectional) was both highly sensitive (100%) and specific (95%) for predicting the need for a neonatal intervention. Parameters for the single-ventricle cohort did not reach statistical significance. CONCLUSIONS: Analysis of the pulmonary outflow tract and ductus arteriosus flow in the fetus with complex congenital heart disease can aid in identifying those that will require a neonatal intervention to augment pulmonary blood flow. This has important implications for the planning of delivery strategies.

Analytical description of the quantum-mesoscopic-classical transition in systems with quasidiscrete environments.

We investigate the dynamic properties of inhomogeneous nanomaterials, which appear in analytical descriptions typically as a series of δ functions with corresponding Gibbs weights. We focus on observables relevant for transport theories of Josephson junction arrays and granular systems near the superconductor-insulator transition. Furthermore, our description applies to the theory of tunnel junctions exchanging energy with a "bath," the latter having a discrete spectrum. Using the matrix θ-function formalism, we find an analytical expression for the transport characteristics capturing the complete temperature-driven transition from the quantum to the classical regime.

Model for dynamic self-assembled magnetic surface structures.

We propose a first-principles model for the dynamic self-assembly of magnetic structures at a water-air interface reported in earlier experiments. The model is based on the Navier-Stokes equation for liquids in shallow water approximation coupled to Newton equations for interacting magnetic particles suspended at a water-air interface. The model reproduces most of the observed phenomenology, including spontaneous formation of magnetic snakelike structures, generation of large-scale vortex flows, complex ferromagnetic-antiferromagnetic ordering of the snake, and self-propulsion of bead-snake hybrids.

Electron transport in nanogranular ferromagnets.

We study electronic transport properties of ferromagnetic nanoparticle arrays and nanodomain materials near the Curie temperature in the limit of weak coupling between the grains. We calculate the conductivity in the Ohmic and non-Ohmic regimes and estimate the magnetoresistance jump in the resistivity at the transition temperature. The results are applicable for many emerging materials, including artificially self-assembled nanoparticle arrays and a certain class of manganites, where localization effects within the clusters can be neglected.

Statistics of deep energy states in Coulomb glasses.

We study the statistics of local energy minima in the configuration space and the energy relaxation due to activated hopping in a system of interacting electrons in a random environment. The distribution of the local minima is exponential, which is in agreement with extreme value statistics considerations. The relaxation of the system energy shows logarithmic time dependence reflecting the ultrametric structure of the system.

Domain wall depinning in random media by ac fields.

The viscous motion of an interface driven by an ac external field of frequency omega(0) in a random medium is considered here in the nonadiabatic regime. The velocity exhibits a smeared depinning transition showing a double hysteresis which is absent in the adiabatic case omega(0)-->0. Using scaling arguments and an approximate renormalization group calculation we explain the main characteristics of the hysteresis loop. In the low frequency limit these can be expressed in terms of the depinning threshold and the critical exponents of the adiabatic case.

The chaperonins of Synechocystis PCC 6803 differ in heat inducibility and chaperone activity.

The chaperonins GroEL and Cpn60 were isolated from the cyanobacterium Synechocystis PCC 6803 and characterized. In cells grown under optimal conditions their ratio was about one to one. However, the amount of GroEL increased considerably more than that of Cpn60 in response to heat stress. The labile chaperonin oligomer required stabilization by MgATP or glycerol during isolation. Use of the E. coli mutant strain, groEL44 revealed that the functional properties of the two cyanobacterial chaperonins are strikingly different. Overexpression of cyanobacterial GroEL in the E. coli mutant strain allowed growth at elevated temperature, the formation of mature bacteriophage T4, and active Rubisco enzyme assembly. In contrast, Cpn60 partially complemented the temperature-sensitive phenotype, the Rubisco assembly defect and did not promote the growth of the bacteriophage T4. The difference in chaperone activity of the two cyanobacterial chaperonins very probably reflects the unique chaperonin properties required during the life of Synechocystis PCC 6803.

Synechocystis HSP17 is an amphitropic protein that stabilizes heat-stressed membranes and binds denatured proteins for subsequent chaperone-mediated refolding.

The small heat shock proteins (sHSPs) are ubiquitous stress proteins proposed to act as molecular chaperones to prevent irreversible protein denaturation. We characterized the chaperone activity of Synechocystis HSP17 and found that it has not only protein-protective activity, but also a previously unrecognized ability to stabilize lipid membranes. Like other sHSPs, recombinant Synechocystis HSP17 formed stable complexes with denatured malate dehydrogenase and served as a reservoir for the unfolded substrate, transferring it to the DnaK/DnaJ/GrpE and GroEL/ES chaperone network for subsequent refolding. Large unilamellar vesicles made of synthetic and cyanobacterial lipids were found to modulate this refolding process. Investigation of HSP17-lipid interactions revealed a preference for the liquid crystalline phase and resulted in an elevated physical order in model lipid membranes. Direct evidence for the participation of HSP17 in the control of thylakoid membrane physical state in vivo was gained by examining an hsp17(-) deletion mutant compared with the isogenic wild-type hsp17(+) revertant Synechocystis cells. We suggest that, together with GroEL, HSP17 behaves as an amphitropic protein and plays a dual role. Depending on its membrane or cytosolic location, it may function as a "membrane stabilizing factor" as well as a member of a multichaperone protein-folding network. Membrane association of sHSPs could antagonize the heat-induced hyperfluidization of specific membrane domains and thereby serve to preserve structural and functional integrity of biomembranes.

Phosphatidylinositol 4,5-bisphosphate regulates two steps of homotypic vacuole fusion.

Yeast vacuoles undergo cycles of fragmentation and fusion as part of their transmission to the daughter cell and in response to changes of nutrients and the environment. Vacuole fusion can be reconstituted in a cell free system. We now show that the vacuoles synthesize phosphoinositides during in vitro fusion. Of these phosphoinositides, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) are important for fusion. Monoclonal antibodies to PI(4,5)P(2), neomycin (a phosphoinositide ligand), and phosphatidylinositol-specific phospholipase C interfere with the reaction. Readdition of PI(4, 5)P(2) restores fusion in each case. Phosphatidylinositol 3-phosphate and PI(3,5)P(2) synthesis are not required. PI(4,5)P(2) is necessary for priming, i.e., for the Sec18p (NSF)-driven release of Sec17p (alpha-SNAP), which activates the vacuoles for subsequent tethering and docking. Therefore, it represents the kinetically earliest requirement identified for vacuole fusion so far. Furthermore, PI(4,5)P(2) is required at a step that can only occur after docking but before the BAPTA sensitive step in the latest stage of the reaction. We hence propose that PI(4,5)P(2) controls two steps of vacuole fusion.

Control of the terminal step of intracellular membrane fusion by protein phosphatase 1.

Intracellular membrane fusion is crucial for the biogenesis and maintenance of cellular compartments, for vesicular traffic between them, and for exo- and endocytosis. Parts of the molecular machinery underlying this process have been identified, but most of these components operate in mutual recognition of the membranes. Here it is shown that protein phosphatase 1 (PP1) is essential for bilayer mixing, the last step of membrane fusion. PP1 was also identified in a complex that contained calmodulin, the second known factor implicated in the regulation of bilayer mixing. The PP1-calmodulin complex was required at multiple sites of intracellular trafficking; hence, PP1 may be a general factor controlling membrane bilayer mixing.

P2Y receptor subtypes differentially couple to inwardly-rectifying potassium channels.

Subtypes of P2Y receptors are well characterized with respect to their agonist profile but little is known about differences in their intracellular signalling properties. When expressed in Xenopus oocytes, both P2Y2 and P2Y6 receptors effectively couple to endogenous Ca2+-dependent Cl--channels. However, only P2Y2 receptors increased currents mediated by inward-rectifier K+ channels of the Kir3.0 subfamily. This increase in Kir-current was sensitive to pertussis toxin, while activation of Ca2+-dependent Cl--channels was not. In contrast, suramin, a P2 receptor antagonist, inhibited activation of both channels. These observations suggest that, in contrast to P2Y6, P2Y2 receptors couple to two different classes of G proteins.

Membrane physical state controls the signaling mechanism of the heat shock response in Synechocystis PCC 6803: identification of hsp17 as a "fluidity gene".

The fluidity of Synechocystis membranes was adjusted in vivo by temperature acclimation, addition of fluidizer agent benzyl alcohol, or catalytic lipid hydrogenation specific to plasma membranes. The reduced membrane physical order in thylakoids obtained by either downshifting growth temperature or administration of benzyl alcohol was paralleled with enhanced thermosensitivity of the photosynthetic membrane. Simultaneously, the stress-sensing system leading to the cellular heat shock (HS) response also has been altered. There was a close correlation between thylakoid fluidity levels, monitored by steady-state 1,6-diphenyl-1,3,5-hexatriene anisotropy, and threshold temperatures required for maximal activation of all of the HS-inducible genes investigated, including dnaK, groESL, cpn60, and hsp17. The causal relationship between the pre-existing thylakoid physical order and temperature set point of both the transcriptional activation and the de novo protein synthesis was the most striking for the 17-kDa HS protein (HSP17) associated mostly with the thylakoid membranes. These findings together with the fact that the in vivo modulation of lipid saturation within cytoplasmic membrane had no effect on HS response suggest that thylakoid acts as a cellular thermometer where thermal stress is sensed and transduced into a cellular signal leading to the activation of HS genes.

Cloning of P2Y6 cDNAs and identification of a pseudogene: comparison of P2Y receptor subtype expression in bone and brain tissues.

Cellular responses to ATP/UTP and analogs are mediated by G-protein coupled P2Y receptors and have been proposed to play a role in the regulation of bone metabolism. Using a degenerate PCR approach on MG-63 cell cDNA we found PCR fragments coding for human P2Y1 and a new receptor, P2Y6. cDNA cloning of the P2Y6 receptor identified three of cDNA isoforms. Two contained the same contiguous ORFs but differed in their 5 UTRs and may therefore originate by alternative splicing whereas the third represents a pseudogene. Analysis of P2Y receptor subtype expression in human bone and the osteoblastic cell lines OHS-4 and MG-63 by RT-PCR showed that all known human P2Y receptor subtypes (P2Y1, P2Y2, P2Y4, P2Y6, and P2Y7) were expressed. In contrast, analysis of brain-derived cell lines suggests that a selective expression of P2Y receptor subtypes occurs in brain tissue.

Chaperonin genes of the Synechocystis PCC 6803 are differentially regulated under light-dark transition during heat stress.

Transcriptional startpoints of the two heat inducible chaperonin genes of Synechocystis PCC 6803 were mapped within the conservative CIRCE element and proved to be identical irrespective of the temperature treatment. Finding of an ORF encoding for a potential CIRCE binding repressor (HrcA) further suggests that both groEL-analogs are regulated in a CIRCE-dependent manner. In contrast to the expectations, the chaperonin twins are differentially expressed under light-dark transition during heat stress. Not the light per se, but rather the photosynthetic electron transport appears to be accountable for the regulatory differences. Our findings support the hypothesis that multiple chaperonins play different physiological roles under stress conditions.

Bimoclomol: a nontoxic, hydroxylamine derivative with stress protein-inducing activity and cytoprotective effects.

Preservation of the chemical architecture of a cell or of an organism under changing and perhaps stressful conditions is termed homeostasis. An integral feature of homeostasis is the rapid expression of genes whose products are specifically dedicated to protect cellular functions against stress. One of the best known mechanisms protecting cells from various stresses is the heat-shock response which results in the induction of the synthesis of heat-shock proteins (HSPs or stress proteins). A large body of information supports that stress proteins--many of them molecular chaperones--are crucial for the maintenance of cell integrity during normal growth as well as during pathophysiological conditions, and thus can be considered "homeostatic proteins." Recently emphasis is being placed on the potential use of these proteins in preventing and/or treating diseases. Therefore, it would be of great therapeutic benefit to discover compounds that are clinically safe yet able to induce the accumulation of HSPs in patients with chronic disorders such as diabetes mellitus, heart disease or kidney failure. Here we show that a novel cytoprotective hydroxylamine derivative, [2-hydroxy-3-(1-piperidinyl) propoxy]-3-pyridinecarboximidoil-chloride maleate, Bimoclomol, facilitates the formation of chaperone molecules in eukaryotic cells by inducing or amplifying expression of heat-shock genes. The cytoprotective effects observed under several experimental conditions, including a murine model of ischemia and wound healing in the diabetic rat, are likely mediated by the coordinate expression of all major HSPs. This nontoxic drug, which is under Phase II clinical trials, has enormous potential therapeutic applications.