Evidence for tuning adipocytes ICER levels for obesity care.

Abnormal adipokine production, along with defective uptake and metabolism of glucose within adipocytes, contributes to insulin resistance and altered glucose homeostasis. Recent research has highlighted one of the mechanisms that accounts for impaired production of adiponectin (ADIPOQ) and adipocyte glucose uptake in obesity. In adipocytes of human obese subjects and mice fed with a high fat diet, the level of the inducible cAMP early repressor (ICER) is diminished. Reduction of ICER elevates the cAMP response element binding protein (CREB) activity, which in turn increases the repressor activating transcription factor 3. In fine, the cascade triggers reduction in the ADIPOQ and GLUT4 levels, which ultimately hampers insulin-mediated glucose uptake. The c-Jun N-terminal kinase (JNK) interacting-protein 1, also called islet brain 1 (IB1), is a target of CREB/ICER that promotes JNK-mediated insulin resistance in adipocytes. A rise in IB1 and c-Jun levels accompanies the drop of ICER in white adipose tissues of obese mice when compared with mice fed with a chow diet. Other than the expression of ADIPOQ and glucose transport, decline in ICER expression might impact insulin signaling. Impairment of ICER is a critical issue that will need major consideration in future therapeutic purposes

Inhaled nitric oxide for high-altitude pulmonary edema

BACKGROUND. Pulmonary hypertension is a hallmark of high-altitude pulmonary edema and may contribute to its pathogenesis. When administered by inhalation, nitric oxide, an endothelium-derived relaxing factor, attenuates the pulmonary vasoconstriction produced by short-term hypoxia. METHODS. We studied the effects of inhaled nitric oxide on pulmonary-artery pressure and arterial oxygenation in 18 mountaineers prone to high-altitude pulmonary edema and 18 mountaineers resistant to this condition in a high altitude laboratory (altitude, 4559 m). We also obtained lung-perfusion scans before and during nitric oxide inhalation to gain further insight into the mechanism of action of nitric oxide. RESULTS. In the high-altitude laboratory, subjects prone to high-altitude pulmonary edema had more pronounced pulmonary hypertension and hypoxemia than subjects resistant to high-altitude pulmonary edema. Arterial oxygen saturation was inversely related to the severity of pulmonary hypertension (r=-0.50, P=0.002). In subjects prone to high-altitude pulmonary edema, the inhalation of nitric oxide (40 ppm for 15 minutes) produced a decrease in mean (+/-SD) systolic pulmonary-artery pressure that was three times larger than the decrease in subjects resistant to such edema (25.9+/-8.9 vs. 8.7+/-4.8 mm Hg, P<0.001). Inhaled nitric oxide improved arterial oxygenation in the 10 subjects who had radiographic evidence of pulmonary edema (arterial oxygen saturation increased from 67+/-10 to 73+/-12 percent, P=0.047), whereas it worsened oxygenation in subjects resistant to high-altitude pulmonary edema. The nitric oxide-induced improvement in arterial oxygenation in subjects with high-altitude pulmonary edema was accompanied by a shift in blood flow in the lung away from edematous segments and toward nonedematous segments. CONCLUSIONS. The inhalation of nitric oxide improves arterial oxygenation in high-altitude pulmonary edema, and this beneficial effect may be related to its favorable action on the distribution of blood flow in the lungs. A defect in nitric nitric oxide synthesis may contribute to high-altitude pulmonary edema

Minimal Model Holography for SO(2N)

A duality between the large N 't Hooft limit of the WD_N minimal model CFTs and a higher spin gravity theory on AdS3 is proposed. The gravity theory has massless spin fields of all even spins s=2,4,6,..., as well as two real scalar fields whose mass is determined by the 't Hooft parameter of the CFT. We show that, to leading order in the large N limit, the 1-loop partition function of the higher spin theory matches precisely with the CFT partition function.Comment: 21 pages, LaTe

Minimal Model Holography

We review the duality relating 2d W_N minimal model CFTs, in a large N 't Hooft like limit, to higher spin gravitational theories on AdS_3.Comment: 54 pages, 1 figure; Contribution to J. Phys. A special volume on "Higher Spin Theories and AdS/CFT" edited by M. R. Gaberdiel and M. Vasiliev. v2. minor change

Already low drug dose antagonism of the renin-angiotensin aldosterone system decreases 1-year mortality and rehospitalization in old heart failure patients

Hospitalization for heart failure treatment (HHF) is an incisive event in the course of HF. Today, the large majority of HHF patients is ≥ 65 years and discharge HF drugs are most often not applied at dose levels acknowledged to provide prognostic benefit. This study therefore aims to investigate the treatment effect size of discharge HF drugs in old HHF patients. Drugs are analyzed according to pharmacological class. Individual discharge HF drug dose is reported as percentage of guidelines-recommended target dose. Primary endpoint was 1-year all-cause mortality (ACM) after discharge; the secondary endpoint combined 1-year ACM and first cardiovascular hospitalization within 1 year after discharge. Comparison between 65-80 years and > 80 years old study participants tested the relative treatment effect size as a function of respective age group. The 875 consecutive HHF patients had a median age of 82 years [76-87 years]; 48.6 % were females. Betablocker and diuretic treatment did not change the incidence of endpoints. Inhibition of the renin-angiotensin system (RASi), when compared to no treatment, decreased the incidence of endpoints both at the 1-25 % and the > 25 % target dose level. Antagonists of the mineralocorticoid receptor (MRA), when compared to no treatment, decreased the secondary endpoint at the 1-25 % target dose level but not at the > 25 % target dose level. The relative treatment effect size of RASi or MRA corresponded between the age strata for both endpoints. Low-dose RASi and MRA had beneficial effects in these old HHF patients

Inorganic carbon promotes photosynthesis, growth, and maximum biomass of phytoplankton in eutrophic water bodies

1.The traditional perception in limnology has been that phytoplankton biomass in lakes is limited by phosphorus, nitrogen, and light, but not by dissolved inorganic carbon (DIC) because CO2 can be supplied from the atmosphere. We tested the possibility of carbon limitation of photosynthesis, growth, and biomass accumulation of phytoplankton communities across an alkalinity and DIC gradient (0.15–3.26 mM) in nutrient‐rich freshwater. 2.During 47‐day long experiments, we measured phytoplankton biomass, organic carbon, calcium, DIC, pH, and oxygen in indoor, constantly mixed mesocosms with either no removal or a 70% weekly removal of the biomass. Photosynthesis was measured in the morning and in the afternoon at high biomass. 3.Maximum biomass and organic carbon production increased two‐ to four‐fold with DIC, which supported 7% of organic carbon production at low DIC and 53% at high DIC concentration, while atmospheric CO2 uptake supplied the remainder. Weekly biomass removal increased growth rates through improved light conditions leading to enhanced total phytoplankton biomass production at high DIC. Photosynthesis was significantly higher in the morning compared to afternoon due to daily DIC depletion. 4.We conclude that phytoplankton photosynthesis, growth rate, maximum biomass, and organic carbon production can be markedly carbon limited in eutrophic lake waters. Consequently, lakes of high DIC and pH can support a faster primary production by greater DIC use and chemically enhanced atmospheric CO2 uptake.publishedVersio

Abnormal brain iron accumulation in obstructive sleep apnea: A quantitative MRI study in the HypnoLaus cohort

Obstructive sleep apnea syndrome (OSA) may be a risk factor for Alzheimer's disease. One of the hallmarks of Alzheimer's disease is disturbed iron homeostasis leading to abnormal iron deposition in brain tissue. To date, there is no empirical evidence to support the hypothesis of altered brain iron homeostasis in patients with obstructive sleep apnea as well. Data were analysed from 773 participants in the HypnoLaus study (mean age 55.9 ± 10.3 years) who underwent polysomnography and brain MRI. Cross-sectional associations were tested between OSA parameters and the MRI effective transverse relaxation rate (R2*) - indicative of iron content - in 68 grey matter regions, after adjustment for confounders. The group with severe OSA (apnea-hypopnea index ≥30/h) had higher iron levels in the left superior frontal gyrus (F3,760 = 4.79, p = 0.003), left orbital gyri (F3,760 = 5.13, p = 0.002), right and left middle temporal gyrus (F3,760 = 4.41, p = 0.004 and F3,760 = 13.08, p < 0.001, respectively), left angular gyrus (F3,760 = 6.29, p = 0.001), left supramarginal gyrus (F3,760 = 4.98, p = 0.003), and right cuneus (F3,760 = 7.09, p < 0.001). The parameters of nocturnal hypoxaemia were all consistently associated with higher iron levels. Measures of sleep fragmentation had less consistent associations with iron content. This study provides the first evidence of increased brain iron levels in obstructive sleep apnea. The observed iron changes could reflect underlying neuropathological processes that appear to be driven primarily by hypoxaemic mechanisms

A Cognitive Model of an Epistemic Community: Mapping the Dynamics of Shallow Lake Ecosystems

We used fuzzy cognitive mapping (FCM) to develop a generic shallow lake ecosystem model by augmenting the individual cognitive maps drawn by 8 scientists working in the area of shallow lake ecology. We calculated graph theoretical indices of the individual cognitive maps and the collective cognitive map produced by augmentation. The graph theoretical indices revealed internal cycles showing non-linear dynamics in the shallow lake ecosystem. The ecological processes were organized democratically without a top-down hierarchical structure. The steady state condition of the generic model was a characteristic turbid shallow lake ecosystem since there were no dynamic environmental changes that could cause shifts between a turbid and a clearwater state, and the generic model indicated that only a dynamic disturbance regime could maintain the clearwater state. The model developed herein captured the empirical behavior of shallow lakes, and contained the basic model of the Alternative Stable States Theory. In addition, our model expanded the basic model by quantifying the relative effects of connections and by extending it. In our expanded model we ran 4 simulations: harvesting submerged plants, nutrient reduction, fish removal without nutrient reduction, and biomanipulation. Only biomanipulation, which included fish removal and nutrient reduction, had the potential to shift the turbid state into clearwater state. The structure and relationships in the generic model as well as the outcomes of the management simulations were supported by actual field studies in shallow lake ecosystems. Thus, fuzzy cognitive mapping methodology enabled us to understand the complex structure of shallow lake ecosystems as a whole and obtain a valid generic model based on tacit knowledge of experts in the field.Comment: 24 pages, 5 Figure

Subanesthetic ketamine treatment promotes abnormal interactions between neural subsystems and alters the properties of functional brain networks

Acute treatment with subanesthetic ketamine, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, is widely utilized as a translational model for schizophrenia. However, how acute NMDA receptor blockade impacts on brain functioning at a systems level, to elicit translationally relevant symptomatology and behavioral deficits, has not yet been determined. Here, for the first time, we apply established and recently validated topological measures from network science to brain imaging data gained from ketamine-treated mice to elucidate how acute NMDA receptor blockade impacts on the properties of functional brain networks. We show that the effects of acute ketamine treatment on the global properties of these networks are divergent from those widely reported in schizophrenia. Where acute NMDA receptor blockade promotes hyperconnectivity in functional brain networks, pronounced dysconnectivity is found in schizophrenia. We also show that acute ketamine treatment increases the connectivity and importance of prefrontal and thalamic brain regions in brain networks, a finding also divergent to alterations seen in schizophrenia. In addition, we characterize how ketamine impacts on bipartite functional interactions between neural subsystems. A key feature includes the enhancement of prefrontal cortex (PFC)-neuromodulatory subsystem connectivity in ketamine-treated animals, a finding consistent with the known effects of ketamine on PFC neurotransmitter levels. Overall, our data suggest that, at a systems level, acute ketamine-induced alterations in brain network connectivity do not parallel those seen in chronic schizophrenia. Hence, the mechanisms through which acute ketamine treatment induces translationally relevant symptomatology may differ from those in chronic schizophrenia. Future effort should therefore be dedicated to resolve the conflicting observations between this putative translational model and schizophrenia

Fisheries management influences phytoplankton biomass of Amazonian floodplain lakes

Tropical floodplains secure the protein supply of millions of people, but only sound management can ensure the long-term continuity of such ecosystem services. Overfishing is a widespread threat to multitrophic systems, but how it affects ecosystem functioning is poorly understood, particularly in tropical freshwater food webs. Models based on temperate lakes frequently assume that primary producers are mostly bottom-up controlled by nutrient and light limitations, with negligible effects of top-down forces. Yet this assumption remains untested in complex tropical freshwater systems experiencing marked spatiotemporal variation. We use consolidated community-based fisheries management practices and spatial zoning to test the relative importance of bottom-up versus top-down drivers of phytoplankton biomass, controlling for the influence of local to landscape heterogeneity. Our study focuses on 58 large Amazonian floodplain lakes under different management regimes that resulted in a gradient of apex-predator abundance. These lakes, distributed along ~600 km of a major tributary of the Amazon River, varied widely in size, structure, landscape context, and hydrological seasonality. Using generalised linear models, we show that community-based fisheries management, which controls the density of apex predators, is the strongest predictor of phytoplankton biomass during the dry season, when lakes become discrete landscape units. Water transparency also emerges as an important bottom-up factor, but phosphorus, nitrogen and several lake and landscape metrics had minor or no effects on phytoplankton biomass. During the wet-season food pulse, when lakes become connected to adjacent water bodies and homogenise the landscape, only lake depth explained phytoplankton biomass. Synthesis and applications. Tropical freshwaters fisheries typically assume that fish biomass is controlled by bottom-up mechanisms, so that overexploitation of large predators would not affect overall ecosystem productivity. Our results, however, show that top-down forces are important drivers of primary productivity in tropical lakes, above and beyond the effects of bottom-up factors. This helps us to understand the enormous success of community-based ‘fishing agreements’ in the Amazon. Multiple stakeholders should embrace socio-ecological management practices that shape both bottom-up and top-down forces to ensure biodiversity protection, sustainable fisheries yields and food security for local communities and regional economies