Nitric oxide activation facilitated by cooperative multimetallic electron transfer within an iron-functionalized polyoxovanadate-alkoxide cluster.

A series of NO-bound, iron-functionalized polyoxovanadate-alkoxide (FePOV-alkoxide) clusters have been synthesized, providing insight into the role of multimetallic constructs in the coordination and activation of a substrate. Upon exposure of the heterometallic cluster to NO, the vanadium-oxide metalloligand is oxidized by a single electron, shuttling the reducing equivalent to the {FeNO} subunit to form a {FeNO}7 species. Four NO-bound clusters with electronic distributions ranging from [VV3VIV2]{FeNO}7 to [VIV5]{FeNO}7 have been synthesized, and characterized via 1H NMR, infrared, and electronic absorption spectroscopies. The ability of the FePOV-alkoxide cluster to store reducing equivalents in the metalloligand for substrate coordination and activation highlights the ultility of the metal-oxide scaffold as a redox reservoir.

Equation of State of Ultracold Fermions in the 2D BEC-BCS Crossover Region.

We report the experimental measurement of the equation of state of a two-dimensional Fermi gas with attractive s-wave interactions throughout the crossover from a weakly coupled Fermi gas to a Bose gas of tightly bound dimers as the interaction strength is varied. We demonstrate that interactions lead to a renormalization of the density of the Fermi gas by several orders of magnitude. We compare our data near the ground state and at finite temperature with predictions for both fermions and bosons from quantum Monte Carlo simulations and Luttinger-Ward theory. Our results serve as input for investigations of close-to-equilibrium dynamics and transport in the two-dimensional system.

Observation of the Berezinskii-Kosterlitz-Thouless Phase Transition in an Ultracold Fermi Gas.

We experimentally investigate the first-order correlation function of a trapped Fermi gas in the two-dimensional BEC-BCS crossover. We observe a transition to a low-temperature superfluid phase with algebraically decaying correlations. We show that the spatial coherence of the entire trapped system can be characterized by a single temperature-dependent exponent. We find the exponent at the transition to be constant over a wide range of interaction strengths across the crossover. This suggests that the phase transitions in both the bosonic regime and the strongly interacting crossover regime are of Berezinskii-Kosterlitz-Thouless type and lie within the same universality class. On the bosonic side of the crossover, our data are well described by the quantum Monte Carlo calculations for a Bose gas. In contrast, in the strongly interacting regime, we observe a superfluid phase which is significantly influenced by the fermionic nature of the constituent particles.

Observation of Pair Condensation in the Quasi-2D BEC-BCS Crossover.

The condensation of fermion pairs lies at the heart of superfluidity. However, for strongly correlated systems with reduced dimensionality the mechanisms of pairing and condensation are still not fully understood. In our experiment we use ultracold atoms as a generic model system to study the phase transition from a normal to a condensed phase in a strongly interacting quasi-two-dimensional Fermi gas. Using a novel method, we obtain the in situ pair momentum distribution of the strongly interacting system and observe the emergence of a low-momentum condensate at low temperatures. By tuning temperature and interaction strength, we map out the phase diagram of the quasi-2D BEC-BCS crossover.

Association of leptin and insulin with childhood obesity and retinal vessel diameters.

OBJECTIVE: Childhood obesity is associated with an impaired retinal microcirculation. The aim of the study was to investigate the association between specific obesity-related biomarkers, physical fitness and retinal vessel diameters in school children. DESIGN AND SUBJECTS: We studied 381 children aged 10-11 years (body mass index (BMI): 19.3±3.7 kg m(-2)) in a school-based setting. MEASUREMENTS: Anthropometric measurements and blood sampling were conducted using standard protocols for children. The serum biomarkers leptin, adiponectin, insulin as well as interleukin-6 (IL-6) were analyzed. Physical fitness was determined by a six-item-test battery and physical activity by use of a questionnaire. Central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE) and the arteriolar-to-venular diameter ratio (AVR) were assessed with a non-mydriatic vessel analyzer (SVA-T) using a computer-based program. RESULTS: Compared with normal weight children (n=254), obese children (n=39) showed higher leptin (P<0.001), higher insulin (P<0.001), higher IL-6 (P<0.001) and lower adiponectin levels (P=0.013). Obese children demonstrated wider CRVE (P=0.041) and lower AVR (P<0.001). Higher leptin levels were associated with wider CRVE (P=0.032) and lower AVR (P=0.010), that was BMI dependent. Insulin levels were associated with arteriolar (P=0.045) and venular dilatation (P=0.034) after adjustment for BMI. No significant associations between adiponectin levels, IL-6 levels, physical fitness or physical activity and retinal vessel diameter were observed. Lower leptin levels were independently correlated with higher physical fitness (r=-0.33; P<0.001). CONCLUSION: Leptin and insulin levels are associated with changes of the retinal microcirculation. Especially insulin seems to be a good target marker for the cardiometabolic risk assessment in children since elevated insulin levels are independently associated with microvascular end-organ alterations at an early stage. Lifestyle intervention studies are warranted to examine whether improvement of physical fitness or weight reduction can affect cardiometabolic risk markers and reverse alterations of the retinal microcirculation.

Retinal vessel diameter, obesity and metabolic risk factors in school children (JuvenTUM 3).

BACKGROUND: The prevalence of childhood obesity is high and its association with future cardiovascular disease in adulthood is well established. The cross-sectional data presented analyze the prevalence of obesity and the association between metabolic risk factors, physical inactivity and retinal vessel diameter in young school children. METHODS: The examination included 578 school children aged 11.1±0.6 years from secondary schools in the District of Munich, Germany. Anthropometric measurements and blood sampling were conducted using standard protocols for children. Physical activity was evaluated by use of a questionnaire. Retinal microvascular diameters and the arteriolar to venular ratio (AVR) were assessed with a non-mydriatic vessel analyser (SVA-T) using a computer-based program. RESULTS: In our population, 128 (22.2%) children were overweight (ow) or obese (ob). The mean retinal arteriolar and venular calibres were 208.0±15.6 µm and 236.2±16.2 µm, respectively, with a mean AVR of 0.88±0.01. Girls had significantly wider arteriolar and venular diameters compared to boys (p<0.001). ow and ob children had a lower AVR compared to normal weight (nw) children (mean(95% CI); nw: 0.89(0.88-0.89); ow: 0.87(0.86-0.88); ob: 0.85(0.83-0.87); p≤0.05). Wider venular diameters were independently associated with higher BMI and higher hsCRP. Blood pressure was associated with retinal vessel constriction. Higher physical inactivity and BMI were independently associated with a reduced AVR (p=0.032 and p<0.001, respectively). CONCLUSIONS: Cardiometabolic risk factors and physical inactivity are associated with retinal microvascular alterations in young children, comparable to associations in adults. Retinal vessel imaging seems to be a feasible assessment for the detection of microvascular impairments in children at risk of developing cardiovascular disease in adulthood.

Electroencephalographic sleep measures in prepubertal depression.

Two nights of electroencephalographic (EEG) sleep recording were performed in a group of prepubertal subjects with major depressive disorder (MDD) (n = 36, mean age = 10.4, SD = 1.5) and age-matched normal control children (n = 18, mean age = 10.1, SD = 1.6). All subjects were medically healthy and free of medications at the time of the study. There were no significant group differences for any major sleep variable after the initial adaptation night in this study. One subgroup of MDD subjects (n = 8) showed reduced REM latency on both recording nights, decreased stage 4 sleep, and increased REM time; this subgroup had significantly higher severity scores for depression but did not otherwise appear to be clinically distinct from the rest of the MDD subjects. Overall, the results indicate that the EEG sleep changes associated with depression in adults occurred less frequently in prepubertal MDD subjects.

Fatty acid stimulated N-demethylation of 1,2-dimethylhydrazine and tetramethylhydrazine by rat colonic mucosa.

A fatty acid stimulated, NADPH-independent pathway for the N-demethylation of 1,1-dimethylhydrazine (1,1-DMH) with the generation of HCHO was demonstrated in 10,000 g soluble fractions of colonic mucosal homogenates. Tetramethylhydrazine and, to a lesser extent, aminopyrine, but not 1,2-DMH or methylhydrazine, were also substrates for this reaction. Isolated superficial colonic epithelial cells metabolized 1,1-DMH at a faster rate than proliferative epithelial cells. Indomethacin, an inhibitor of cyclooxygenase activity, and 5,8,11,14-eicosatetraynoic acid (ETYA), an inhibitor of both cyclooxygenase and lipoxygenase activities, suppressed HCHO production from 1,1-DMH by 50 and 80%. However, in the presence of indomethacin or ETYA, arachidonate hydroperoxide stimulated HCHO formation. This suggested a peroxidative mechanism for 1,1-DMH metabolism, related in part to prostaglandin synthesis. A possible role for lipoxygenase activity in mediating 1,1-DMH metabolism was suggested by the ability of linoleate, which did not increase prostaglandin synthesis, to stimulate 1,1-DMH metabolism and by the fact that ETYA was more effective than indomethacin as an inhibitor of 1,1-DMH metabolism. The fatty acid stimulated pathway for N-demethylation was clearly distinct from the mixed function oxidase activities. NADPH did not stimulate 1,1-DMH metabolism to HCHO. 7,8-Benzoflavone or SKF-525A, inhibitors of cytochrome P-450, and methimazole, an inhibitor of N-demethylation catalyzed by the hepatic microsomal FAD-containing monooxygenase, did not suppress HCHO formation. To the extent that 1,1-DMH and tetramethylhydrazine reach the colon unchanged, the results suggest that fatty acid stimulated cooxidation pathways in colonic mucosa may contribute to the metabolism of these agents. Metabolism by superficial cells which are destined to slough may be an important defense mechanism against the toxic and carcinogenic actions of these hydrazines in colon.

Fatty acid-stimulated oxidation of methylazoxymethanol by rat colonic mucosa.

The present study examined fatty acid-initiated metabolism of methylazoxymethanol (MAM) to formaldehyde (HCHO) by the 10,000 X g soluble fraction of rat colonic mucosa, and the role of prostaglandin synthase and lipoxygenase activities in mediating this process. Incubation of MAM with soluble fractions of rat colonic mucosa, in the absence of arachidonate, resulted in significant HCHO production compared to that observed in buffer alone or with the heated tissue fractions. Addition of arachidonate (100 microM), linoleate (100 microM), or arachidonate hydroperoxide, but not palmitate, increased HCHO formation by 50%. Indomethacin (25 to 100 microM) suppressed basal and arachidonate-stimulated HCHO production by 25 to 50%. However, indomethacin did not influence linoleate or arachidonate hydroperoxide-induced increases in HCHO. These data suggested a peroxidative mechanism for MAM oxidation, that was mediated in part by arachidonate metabolism via the prostaglandin synthase system. 5,8,11,14-Eicosatetraynoic acid (25 to 500 microM) suppressed HCHO production by 30 to 80% in the absence of fatty acids, and abolished stimulation by arachidonate or linoleate, but not by arachidonate hydroperoxide. MAM was also oxidized by an NAD+-dependent dehydrogenase, as evidenced by MAM-mediated NAD reduction in 10,000 X g soluble fractions of rat colonic mucosa. On a molar basis, the ability of the soluble fraction of rat colonic mucosa to oxidize MAM by the NAD+-dependent dehydrogenase pathway and the fatty acid-stimulated pathway were similar. However, NADPH did not stimulate HCHO formation by MAM. Moreover, 7,8-naphthoflavone; 2-diethylaminoethyl-2,2-diphenylvalerate; and methimazole, inhibitors of mixed-function oxidase activity, did not suppress HCHO formation, implying that MAM was not metabolized by the colonic mixed-function oxidase activity. MAM metabolism to HCHO was 3 to 4 times greater by soluble fractions of superficial epithelial cells isolated from rat colon compared to those of the isolated proliferative epithelial cell pool. The results are consistent with a role for both the prostaglandin synthase and lipoxygenase systems of colonic mucosa in the oxidative metabolism of MAM. Enhanced oxidation of MAM by superficial cells of colonic epithelium which are preparing to slough may serve to protect the colon against the carcinogenic effect of this drug.

Properties of multiple kinetic forms of soluble cyclic nucleotide phosphodiesterase activity of rat colonic mucosa.

Soluble phosphodiesterase (EC 3.1.4.1) activity is 3-5-fold lower in superficial colonic epithelial cells compared to that in cells isolated from the lower colonic crypt. Higher phosphodiesterase activity in lower crypt cells is correlated with a 5-fold higher rate of incorporation of [3H]thymidine into DNA in these cells. DEAE-cellulose chromatography of the soluble fraction of superficial and proliferative colonic epithelial cells resulted in separation of three enzyme forms: (1) fraction I, an enzyme which hydrolyzes both cAMP and cGMP with high affinity (apparent Km cAMP = 5 +/- 1 microM, Km cGMP = 2.5 +/- 0.5 microM) and is stimulated 3-6-fold by Ca2+ plus calmodulin; (2) fraction II, a form which hydrolyzes both cAMP and cGMP with low affinity (S0.5 cAMP = 52 +/- 7 microM, S0.5 cGMP = 17 +/- 4 microM), exhibits positive copperativity with respect to substrate and shows cGMP stimulation of cAMP hydrolysis and (3) fraction III, a cAMP-specific form which exhibits biphasic kinetics, a low Km for cAMP (Km cAMP = 5 +/- 1 microM) and does not hydrolyze cGMP. The pattern of distribution of phosphodiesterase activities on DEAE-cellulose was similar in superficial and proliferative colonic epithelial cells. The higher specific activity in proliferative cells was reflected in higher activities of each of the three chromatographically distinct forms of the enzyme. In contrast to epithelial cells, the soluble fraction of homogenates of the submucosa and supporting cells exhibited phosphodiesterase forms I and II and was lacking in the form corresponding to fraction III of epithelial cells.