Negative velocity fluctuations and non-equilibrium fluctuation relation for a driven high critical current vortex state.

Under the influence of a constant drive the moving vortex state in 2H-NbS2 superconductor exhibits a negative differential resistance (NDR) transition from a steady flow to an immobile state. This state possesses a high depinning current threshold ([Formula: see text]) with unconventional depinning characteristics. At currents well above [Formula: see text], the moving vortex state exhibits a multimodal velocity distribution which is characteristic of vortex flow instabilities in the NDR regime. However at lower currents which are just above [Formula: see text], the velocity distribution is non-Gaussian with a tail extending to significant negative velocity values. These unusual negative velocity events correspond to vortices drifting opposite to the driving force direction. We show that this distribution obeys the Gallavotti-Cohen Non-Equilibrium Fluctuation Relation (GC-NEFR). Just above [Formula: see text], we also find a high vortex density fluctuating driven state not obeying the conventional GC-NEFR. The GC-NEFR analysis provides a measure of an effective energy scale (E eff ) associated with the driven vortex state. The E eff corresponds to the average energy dissipated by the fluctuating vortex state above [Formula: see text]. We propose the high E eff value corresponds to the onset of high energy dynamic instabilities in this driven vortex state just above [Formula: see text].

Sodium-Calcium Exchanger in Pig Coronary Artery.

This review focuses on the sodium-calcium exchangers (NCX) in the left anterior descending coronary artery smooth muscle. Bathing tissues in Na+-substituted solutions caused them to contract. In cultured smooth muscle cells, it increased the cytosolic Ca2+ concentration and extracellular entry of 45Ca2+. All three activities were attributed to NCX since they were inhibited by NCX inhibitors. The tissues also expressed the sarco/endoplasmic reticulum (SER) Ca2+ pump SERCA2b whose activity was much greater than that of NCX. Inhibiting SERCA2b with thapsigargin decreased the NCX-mediated 45Ca2+ accumulation by the cells. The decrease was not observed in cells loaded with the Ca2+-chelator BAPTA. The results are consistent with a limited diffusional space model with a proximity between NCX and SERCA2b. NCX molecules appear to be colocalized with the subsarcolemmal SERCA2b based on studies on membrane flotation experiments and microscopic fluorescence imaging of antibody-labeled cells. Thapsigargin inhibition of SERCA2b moved NCX even closer to SER. This provides a model for the NCX-mediated Ca2+ refilling of SER in the arterial smooth muscle. The model for the NCX-mediated refilling of the depleted SER proposed for smooth muscle did not apply to endothelium in which NCX levels were greater and SERCA levels were lower than in smooth muscle. The effect of thapsigargin on the NCX-mediated Ca2+ accumulation which was observed in smooth muscle was absent in the endothelium. We propose that the coupling between NCX and smooth muscle may be tissue dependent.

Study of the sign change of exchange bias across the spin reorientation transition in Co(Cr1-x Fe x )2O4 (x = 0.00-0.125).

We present the evolution of novel phenomena of magnetic compensation effect, exchange bias (EB) effect and the field induced anomalies in '[Formula: see text]' substituted multiferroic compound [Formula: see text]. A few percent of '[Formula: see text]' substitution for '[Formula: see text]' in [Formula: see text] results in the reversal of field cooled magnetization under low applied fields below compensation temperature T comp. Further, increase in the field leads to the spin reorientation transition (T SR). Signature of EB in a narrow temperature window in the vicinity of T SR and its sign change across T SR is observed. Magnitude of EB depends on the amount of compensation and rigidity of the spin reorientation. We also notice the appearance of positive EB below the lock-in transition (T L). Presence of unidirectional anisotropy developed in the commensurate spin-spiral below T L could be responsible for the appearance of EB below T L.

Paramagnetic magnetization signals and curious metastable behaviour in field-cooled magnetization of a single crystal of superconductor 2H-NbSe2.

We present here some newer characteristics pertaining to paramagnetic Meissner effect like response in a single crystal of the low [Formula: see text] superconducting compound 2H-[Formula: see text] via a detailed study of effects of perturbation on the field-cooled magnetization response. In the temperature range, where an anomalous paramagnetic magnetization occurs, the field-cooled magnetization response is found to be highly metastable: it displays a curious tendency to switch randomly from a given paramagnetic value to a diamagnetic or to a different paramagnetic value, when the system is perturbed by an impulse of an externally applied ac magnetic field. The new facets revealed in a single crystal of 2H-[Formula: see text] surprisingly bear a marked resemblance with the characteristics of magnetization behaviour anticipated for the giant vortex states with multiple flux quanta ([Formula: see text], [Formula: see text], [Formula: see text]) predicted to occur in mesoscopic-sized superconducting specimen and possible transitions amongst such states.

Eyelid nodule: a rare presentation of Langerhans cell histiocytosis.

Langerhans cell histiocytosis occurring as an isolated tumor of eyelid has rarely been reported. We report an unusual case of a 5-year-old boy who presented with a smooth nodular lesion over the right lower eyelid accompanied with hyperemia for a month. The biopsy and CD1a positivity confirmed it to be Langerhans cell histiocytosis. It was localized to the eyelid as no other organ was involved. Although Langerhans cell histiocytosis of the eyelid is exceptional, it must be included in the differential diagnosis of eyelid nodular lesions and the diagnostic and the subsequent management must be multidisciplinary.

Magnetic response in the vicinity of magnetic compensation: a case study in spin ferromagnetic Sm1 - xGdxAl2 intermetallic alloys.

A compensated magnetic state in an ideally homogeneous system with long range magnetic order is characterized by a net zero magnetization (M) throughout the sample (macroscopic). In the pristine state of the sample (i.e. with no external field, H = 0), this implies that at the magnetic compensation temperature (Tcomp) we must have M = 0 at H = 0 irrespective of any thermal and magnetic history of the sample and any underlying physics. This simple fact voids the usual identification (and interpretation) of M-H loop parameters at and in the vicinity of magnetic compensation temperature, specifically the coercivity, the remanence, and the exchange bias characteristics. The physics of coercivity and exchange bias continues to be fully relevant, but its manifestation in an M-H loop would get camouflaged at (and near) a magnetic compensation because [Formula: see text] at H = 0. We present an experimental elucidation of the above premise through a case study in the spin ferromagnetic Sm1 - xGdxAl2 alloys [x = 0.01-0.06], where the specimens with x ≤ 0.03 show compensation below the Curie temperature Tc, while those with x ≥ 0.03 have rather small magnetization due to near cancellation of opposing contributions, but are otherwise devoid of compensation. The experiments comprised low field (near zero) as well as high field (70 kOe) magnetization measurements from the paramagnetic state down to 5 K in the ordered regime (Tc ∼ 125 K) and isothermal M-H loop studies on the remnant magnetic state of polycrystalline samples.

Large low-frequency fluctuations in the velocity of a driven vortex lattice in a single crystal of 2H-NbSe2 superconductor.

The driven state of a well-ordered flux line lattice in a single crystal of 2H-NbSe2 in the time domain has revealed the presence of substantial fluctuations in velocity, with large and distinct time periods ( approximately seconds). A superposition of a periodic drive in the driven vortex lattice causes distinct changes in these fluctuations. We propose that prior to the onset of the peak effect there exists a heretofore unexplored regime of coherent dynamics, with unexpected behavior in velocity fluctuations.

Plasma membrane calcium pump activity in rat pancreatic islets: an accurate method to measure its calcium-dependent modulation.

The aim of this study was to quantify the glucose modulation of the plasma membrane calcium pump (PMCA) function in rat pancreatic islets. Ca2+-ATPase activity and levels of phosphorylated PMCA intermediates both transiently declined to a minimum in response to stimulation by glucose. Strictly dependent on Ca2+ concentration, this inhibitory effect was fully expressed at physiological concentrations of the cation (less than 0.5 muM), then progressively diminished at higher concentrations. These results, together with those previously reported on the effects of insulin secretagogues and blockers on the activity, expression and cellular distribution of the PMCA, support the concept that the PMCA plays a key role in the regulation of Ca2+ signaling and insulin secretion in pancreatic islets.

Leber's hereditary optic neuropathy with molecular characterization in two Indian families.

PURPOSE: Leber's hereditary optic neuropathy (LHON) presents in early adulthood with painless progressive blindness of one or both eyes. Usually there is a positive family history of similar disease on the maternal side. Definitive diagnosis can be established by finding the change in the mitochondrial gene. No molecular studies have been reported from India. MATERIAL AND METHODS: Clinical, ophthalmologic and molecular studies were carried out in two patients from different families and available first degree relatives. The subjects were tested for the three common mutations seen in LHON by molecular techniques of polymerase chain reaction using mutation specific primers. RESULTS: The mutations G3460A and G11778A in the mitochondrial genes MTND1 and MTND4, known to be causative for LHON, were found in one family each. CONCLUSION: Diagnosis of LHON should be considered in familial cases and in young adults with optic atrophy. Confirmation of diagnosis should be sought by molecular gene analysis. Genetic counselling should be offered to all 'at risk' relatives of a patient harbouring the mutation.

Mechanism of action of the novel plasma membrane Ca(2+)-pump inhibitor caloxin.

Caloxin 2A1 is a novel inhibitor of the plasma membrane (PM) Ca(2+)-pump [Am. J. Physiol. Cell Physiol. 280 (2001) C1027]. The PM Ca(2+)-pump is a Ca(2+)-Mg(2+)-ATPase that expels Ca(2+) from cells to help them maintain low concentrations of cytosolic Ca(2+). Caloxin 2A1 inhibits Ca(2+)-Mg(2+)-ATPase in human erythrocyte leaky ghosts. Here we report that this inhibition is non-competitive with respect to the substrates Ca(2+) and ATP and the activator calmodulin. This was anticipated since the high affinity binding site for Ca(2+) and sites for ATP and calmodulin are intracellular whereas caloxin 2A1 is a peptide selected for binding to the second extracellular domain of the pump. Caloxin 2A1 also inhibited the Ca(2+)-dependent formation of the acid stable 140 kDa acylphosphate intermediate from 32P-gamma-ATP. However, it did not inhibit the formation of the acylphosphate intermediate in the reverse direction-from 32P-orthophosphate. Consistent with results on mutagenesis of transmembrane residues in the pump protein, we suggest that caloxin 2A1 inhibits conformational changes required during the reaction cycle of the pump.

Iron promotes cadmium binding to citrate.

Iron-cadmium interactions are important in cadmium toxicity. Dietary iron supplements may decrease cadmium retention after oral cadmium exposure but the underlying mechanism is not known. Using a CdS/AgS ion selective electrode to measure [Cd2+] in physiological saline solution at pH 7.4, we show that Fe2+ promotes Cd2+ binding to citrate thereby decreasing the availability of free Cd2+. This suggests the formation of high molecular weight Cd2+-Fe2+-citrate complexes. We confirm this suggestion by showing that 109Cd2+ is retained by 1 kDa cut off filters when present with total 50 microM Fe2+ plus 1 mM citrate but not when present with citrate alone. The formation of high molecular weight complexes may prevent Cd2+ absorption. As citrate is part of the diet, we suggest that these iron-cadmium interactions may contribute to the protective effect of iron against cadmium toxicity.

The role of 3'-untranslated region (3'-UTR) mediated mRNA stability in cardiovascular pathophysiology.

Knowledge of transcription and translation has advanced our understanding of cardiac diseases. Here, we present the hypothesis that the stability of mRNA mediated by the 3'-untranslated region (3'-UTR) plays a role in changing gene expression in cardiovascular pathophysiology. Several proteins that bind to sequences in the 3'-UTR of mRNA of cardiovascular targets have been identified. The affected mRNAs include those encoding beta-adrenergic receptors, angiotensin II receptors, endothelial and inducible nitric oxide synthases, cyclooxygenase, endothelial growth factor, tissue necrosis factor (TNF-alpha), globin, elastin, proteins involved in cell cycle regulation, oncogenes, cytokines and lymphokines. We discuss: (a) the types of 3'-UTR sequences involved in mRNA stability, (b) AUF1, HuR and other proteins that bind to these sequences to either stabilize or destabilize the target mRNAs, and (c) the potential role of the 3'-UTR mediated mRNA stability in heart failure, myocardial infarction and hypertension. We hope that these concepts will aid in better understanding cardiovascular diseases and in developing new therapies.

Treatment of PC12 cells with nerve growth factor increases iron uptake.

Phaeochromocytoma PC12 cells treated with nerve growth factor (NGF) differentiate into a neuronal phenotype. Here we compare the uptake of transferrin-bound and non-transferrin-bound iron in NGF-treated (neuronal phenotype) and control (proliferating) PC12 cells. The non-transferrin-bound iron uptake was greater in the NGF-treated cells than in the control, independently of the uptake time, the iron-chelating agents used, the oxidation state of iron (Fe(2+) or Fe(3+)) and the iron concentration tested. The NGF-treated cells expressed L-type and N-type voltage-operated Ca(2+) channels. Nitrendipine (an L-type inhibitor) and possibly omega-conotoxin (an N-type inhibitor) inhibited the iron uptake by 20%. Thapsigargin inhibits the endoplasmic reticulum Ca(2+) pump and allowed Mn(2+) entry into cells. Preincubating PC12 cells with thapsigargin increased the iron uptake. The rate of transferrin-bound iron uptake was less than 1% of the non-transferrin-bound iron uptake and the maximum transferrin-bound iron uptake was also very low. We conclude that an increase in the iron uptake by multiple pathways accompanies the transition of PC12 cells from the proliferating to the neuronal phenotype.

Caloxin: a novel plasma membrane Ca2+ pump inhibitor.

Plasma membrane (PM) Ca2+ pump is a Ca+-Mg2+-ATPase that expels Ca2+ from cells to help them maintain low concentrations of cytosolic Ca2+ . There are no known extracellularly acting PM Ca2+ pump inhibitors, as digoxin and ouabain are for Na+ pump. In analogy with digoxin, we define caloxins as extracellular PM Ca2+ pump inhibitors and describe caloxin 2A1. Caloxin 2A1 is a peptide obtained by screening a random peptide phage display library for binding to the second extracellular domain (residues 401-413) sequence of PM Ca2+ pump isoform 1b. Caloxin 2A1 inhibits Ca2+-Mg2+-ATPase in human erythrocyte leaky ghosts, but it does not affect basal Mg2+-ATPase or Na+-K+-ATPase in the ghosts or Ca2+-Mg2+-ATPase in the skeletal muscle sarcoplasmic reticulum. Caloxin 2A1 also inhibits Ca2+-dependent formation of the 140-kDa acid-stable acylphosphate, which is a partial reaction of this enzyme. Consistent with inhibition of the PM Ca2+ pump in vascular endothelium, caloxin 2A1 produces an endothelium-dependent relaxation that is reversed by N(G)-nitro-L-arginine methyl ester. Thus caloxin 2A1 is a novel PM Ca2+ pump inhibitor selected for binding to an extracellular domain.

Transient receptor potential protein mRNA expression in rat substantia nigra.

Receptor gated Ca2+ entry has been associated with transient receptor potential (TRP) proteins encoded by several different genes. Here, we compare expression of mRNA for TRP isoforms encoded by genes TRP1-6 in the rat substantia nigra and whole brain. The substantia nigra and the whole brain expressed mRNA predominantly for TRP3 and TRP6. The levels of TRP1, 2, 4 and 5 were very low in both. The TRP6 mRNA levels in substantia nigra and the whole brain were comparable while those for TRP3 were significantly lower in substantia nigra than in the whole brain. Thus substantia nigra differs from the whole brain in its TRP expression.

Ascorbate transport in pig coronary artery smooth muscle: Na(+) removal and oxidative stress increase loss of accumulated cellular ascorbate.

Pig deendothelialized coronary artery rings and smooth muscle cells cultured from them accumulated ascorbate from medium containing Na(+). The accumulated material was determined to be ascorbate using high-performance liquid chromatography. We further characterized ascorbate uptake in the cultured cells. The data fitted best with a Hill coefficient of 1 for ascorbate (K(asc) = 22 +/- 2 microM) and 2 for Na(+) (K(Na) = 84 +/- 10 mM). The anion transport inhibitors sulfinpyrazone and 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS) inhibited the uptake. Transferring cultured cells loaded with (14)C-ascorbate into an ascorbate-free solution resulted in a biphasic loss of radioactivity - an initial sulfinpyrazone-insensitive faster phase and a late sulfinpyrazone-sensitive slower phase. Transferring loaded cells into a Na(+)-free medium increased the loss in the initial phase in a sulfinpyrazone-sensitive manner, suggesting that the ascorbate transporter is bidirectional. Including peroxide or superoxide in the solution increased the loss of radioactivity. Thus, ascorbate accumulated in coronary artery smooth muscle cells by a Na(+)-dependent transporter was lost in an ascorbate-free solution, and the loss was increased by removing Na(+) from the medium or by oxidative stress.

Effects of hydrogen peroxide on pig coronary artery endothelium.

Peroxides and other reactive oxygen species damage arteries during ischemia-reperfusion. Here, we report on the effects of H(2)O(2) on contractility of pig coronary artery. We either treated 3-mm coronary artery rings with 0 to 0.5 mM H(2)O(2) in organ baths or we perfused the arteries with H(2)O(2) and then cut them into rings. In each instance, we monitored the force of contraction of 3-mm rings in H(2)O(2)-free solution with 30 mM KCl and then we determined the A23187 induced endothelium dependent relaxation as a percent of this contraction. Treatment with H(2)O(2) in the organ bath caused a decrease in the contraction but it did not affect the percent relaxation. Treating arteries with H(2)O(2) by luminal perfusion did not affect the contraction but it decreased the percent relaxation. Perfusion alone decreased the amount of endothelium remaining in the arteries and perfusing with H(2)O(2) decreased it further. The percent relaxation with A23187 correlated well with the endothelium remaining in the arteries. We propose that H(2)O(2) and shear stress can cause a loss of endothelium and that endothelium can also protect the underlying smooth muscle against luminal H(2)O(2).