Permanent porosity in lantern-type M
4
L
4
paddlewheel-based cages is rare and has only been reported for naphthalene, naphthyridine, and diethynylbenzene-based linkers. This work presents the ...design, synthesis, and characterization of small lanterns that exhibit CO
2
accessible BET surface areas in excess of 200 m
2
g
−1
. The crystal packing and porosity of these cages can be tuned by either ligand functionalization or the choice of M
2+
source used in their synthesis. Given their low nuclearity, these cages with internal M-M distances of less than 5 Å represent the lower size limit for permanently microporous coordination cages.
This work presents the design, synthesis, and characterization of small lanterns with BET surface areas in excess of 200 m
2
g
−1
. These cages represent the lower size limit for permanently microporous coordination cages.
Hypoxic pulmonary vasoconstriction (HPV) optimizes the match between ventilation and perfusion in the lung by reducing blood flow to poorly ventilated regions. Sepsis and endotoxemia impair HPV. We ...previously showed that nitric oxide synthase 2 (NOS2) is required, but not sufficient, for the effect of endotoxin on HPV. The aim of the current study was to identify additional factors that might contribute to the impairment of HPV during endotoxemia.
Gene expression profiling was determined using pulmonary tissues from NOS2-deficient (NOS2
) and wild-type mice subjected to endotoxin or saline challenge (control). HPV was accessed as the percentage increase in left pulmonary vascular resistance (LPVR) in response to left main bronchus occlusion (LMBO) in wild-type mice.
Among the 22,690 genes analyzed, endotoxin induced a greater than three-fold increase in 59 and 154 genes in the lungs of wild-type and NOS2
mice, respectively. Of all the genes induced by endotoxin in wild-type mice, arginase 1 (Arg1) showed the greatest increase (16.3-fold compared to saline treated wild-type mice). In contrast, endotoxin did not increase expression of Arg1 in NOS2
mice. There was no difference in the endotoxin-induced expression of Arg2 between wild-type and NOS2-deficient mice. We investigated the role of arginase in HPV by treating the mice with normal saline or the arginase inhibitor N
-hydroxy-nor-L-arginine (norNOHA). In control mice (in the absence of endotoxin) treated with normal saline, HPV was intact as determined by profound LMBO-induced increase in LPVR (121 ± 22% from baseline). During endotoxemia and treatment with normal saline, HPV was impaired compared to normal saline treated control mice (33 ± 9% vs. 121 ± 22%, P < 0.05). HPV was restored in endotoxin-exposed mice after treatment with the arginase inhibitor norNOHA as shown by the comparison to endotoxemic mice treated with normal saline (113 ± 29% vs, 33 ± 9%, P < 0.05) and to control mice treated with normal saline (113 ± 29% vs, 121 ± 22%, P = 0.97).
The results of this study suggest that endotoxemia induces Arg1 and that arginase contributes to the endotoxin-induced impairment of HPV in mice.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The quantum sieving effect between D2 and H2 is examined for a series of metal–organic frameworks (MOFs) over the temperature range 77–150 K. Isothermal adsorption measurements demonstrate a ...consistently larger isosteric heat of adsorption for D2 vs H2, with the largest difference being 1.4 kJ/mol in the case of Ni-MOF-74. This leads to a low-pressure selectivity for this material that increases from 1.5 at 150 K to 5.0 at 77 K. Idealized adsorption solution theory indicates that the selectivity decreases with increasing pressure, but remains well above unity at ambient pressure. Infrared measurements on different MOF materials show a strong correlation between selectivity and the frequency of the adsorbed H2 translational band. This confirms that the separation is predominantly due to the difference in the zero-point energies of the adsorbed isotopologues.
Pronounced changes in fauna, extending from the English Channel in the south to the Barents Sea in the north-east and off Greenland in the north-west, have occurred in the late 1920s, the late 1960s ...and again in the late 1990s. We attribute these events to exchanges of subarctic and subtropical water masses in the north-eastern North Atlantic Ocean, associated with changes in the strength and extent of the subpolar gyre. These exchanges lead to variations in the influence exerted by the subarctic or Lusitanian biomes on the intermediate faunistic zone in the north-eastern Atlantic. This strong and persistent bottom-up bio-physical link is demonstrated using a numerical ocean general circulation model and data on four trophically connected levels in the food chain - phytoplankton, zooplankton, blue whiting, and pilot whales. The plankton data give a unique basin-scale depiction of these changes, and a long pilot whale record from the Faroe Islands offers an exceptional temporal perspective over three centuries. Recent advances in simulating the dynamics of the subpolar gyre suggests a potential for predicting the distribution of the main faunistic zones in the north-eastern Atlantic a few years into the future, which might facilitate a more rational management of the commercially important fisheries in this region.
Elevated resting pulmonary arterial pressure (PAP) in patients with left ventricular systolic dysfunction (LVSD) purports a poor prognosis. However, PAP response patterns to exercise in LVSD and ...their relationship to functional capacity and outcomes have not been characterized.
Sixty consecutive patients with LVSD (age 60±12 years, left ventricular ejection fraction 0.31±0.07, mean±SD) and 19 controls underwent maximum incremental cardiopulmonary exercise testing with simultaneous hemodynamic monitoring. During low-level exercise (30 W), LVSD subjects, compared with controls, had greater augmentation in mean PAPs (15±1 versus 5±1 mm Hg), transpulmonary gradients (5±1 versus 1±1 mm Hg), and effective pulmonary artery elastance (0.05±0.02 versus -0.03±0.01 mm Hg/mL, P<0.0001 for all). A linear increment in PAP relative to work (0.28±0.12 mm Hg/W) was observed in 65% of LVSD patients, which exceeded that observed in controls (0.07±0.02 mm Hg/W, P<0.0001). Exercise capacity and survival was worse in patients with a PAP/watt slope above the median than in patients with a lower slope. In the remaining 35% of LVSD patients, exercise induced a steep initial increment in PAP (0.41±0.16 mm Hg/W) followed by a plateau. The plateau pattern, compared with a linear pattern, was associated with reduced peak Vo(2) (10.6±2.6 versus 13.1±4.0 mL · kg(-1) · min(-1), P=0.005), lower right ventricular stroke work index augmentation with exercise (5.7±3.8 versus 9.7±5.0 g/m(2), P=0.002), and increased mortality (hazard ratio 8.1, 95% CI 2.7 to 23.8, P<0.001).
A steep increment in PAP during exercise and failure to augment PAP throughout exercise are associated with decreased exercise capacity and survival in patients with LVSD, and may therefore represent therapeutic targets.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00309790.
Therapeutic hypothermia (TH) improves neurological outcomes after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Although nitric oxide prevents organ injury induced by ischemia and ...reperfusion, role of nitric oxide during TH after CPR remains unclear. In this article, the authors examined the impact of endogenous nitric oxide synthesis on the beneficial effects of hypothermia after CA/CPR. The authors also examined whether or not inhaled nitric oxide during hypothermia further improves outcomes after CA/CPR in mice treated with TH.
Wild-type mice and mice deficient for nitric oxide synthase 3 (NOS3(−/−)) were subjected to CA at 37 °C and then resuscitated with chest compression. Body temperature was maintained at 37 °C (normothermia) or reduced to 33 °C (TH) for 24 h after resuscitation. Mice breathed air or air mixed with nitric oxide at 10, 20, 40, 60, or 80 ppm during hypothermia. To evaluate brain injury and cerebral blood flow, magnetic resonance imaging was performed in wild-type mice after CA/CPR.
Hypothermia up-regulated the NOS3-dependent signaling in the brain (n = 6 to 7). Deficiency of NOS3 abolished the beneficial effects of hypothermia after CA/CPR (n = 5 to 6). Breathing nitric oxide at 40 ppm improved survival rate in hypothermia-treated NOS3(−/−) mice (n = 6) after CA/CPR compared with NOS3(−/−) mice that were treated with hypothermia alone (n = 6; P < 0.05). Breathing nitric oxide at 40 (n = 9) or 60 (n = 9) ppm markedly improved survival rates in TH-treated wild-type mice (n = 51) (both P < 0.05 vs. TH-treated wild-type mice). Inhaled nitric oxide during TH (n = 7) prevented brain injury compared with TH alone (n = 7) without affecting cerebral blood flow after CA/CPR (n = 6).
NOS3 is required for the beneficial effects of TH. Inhaled nitric oxide during TH remains beneficial and further improves outcomes after CA/CPR. Nitric oxide breathing exerts protective effects after CA/CPR even when TH is ineffective due to impaired endogenous nitric oxide production.
Near-field thermal emission largely exceeds blackbody radiation, owing to spectrally sharp emission in surface polaritons. We turn the Casimir-Polder interaction between Cs(7P_{1/2}) and a sapphire ...interface into a sensor sharply filtering, at 24.687 THz, the near-field sapphire emission at ∼24.5 THz. The temperature evolution of the sapphire mode is demonstrated. The Cs sensor, sensitive to both dispersion and dissipation, suggests the polariton to be redshifted and sharper, as compared, up to 1100 K, to predictions from far-field sapphire emission, affected by birefringence and multiple resonances.
The aim of this study was to investigate the changes induced by high tidal volume ventilation (HVTV) in pulmonary expression of micro-RNAs (miRNAs) and identify potential target genes and ...corresponding miRNA-gene networks. Using a real-time RT-PCR-based array in RNA samples from lungs of mice subjected to HVTV for 1 or 4 h and control mice, we identified 65 miRNAs whose expression changed more than twofold upon HVTV. An inflammatory and a TGF-β-signaling miRNA-gene network were identified by in silico pathway analysis being at highest statistical significance (P = 10(-43) and P = 10(-28), respectively). In the inflammatory network, IL-6 and SOCS-1, regulated by miRNAs let-7 and miR-155, respectively, appeared as central nodes. In TGF-β-signaling network, SMAD-4, regulated by miR-146, appeared as a central node. The contribution of miRNAs to the development of lung injury was evaluated in mice subjected to HVTV treated with a precursor or antagonist of miR-21, a miRNA highly upregulated by HVTV. Lung compliance was preserved only in mice treated with anti-miR-21 but not in mice treated with pre-miR-21 or negative-control miRNA. Both alveolar-arterial oxygen difference and protein levels in bronchoalveolar lavage were lower in mice treated with anti-miR-21 than in mice treated with pre-miR-21 or negative-control miRNA (D(A-a): 66 ± 27 vs. 131 ± 22, 144 ± 10 mmHg, respectively, P < 0.001; protein concentration: 1.1 ± 0.2 vs. 2.3 ± 1, 2.1 ± 0.4 mg/ml, respectively, P < 0.01). Our results show that HVTV induces changes in miRNA expression in mouse lungs. Modulation of miRNA expression can affect the development of HVTV-induced lung injury.
Epigenetic silencing of fragile X mental retardation 1 (FMR1) causes fragile X syndrome (FXS), a common inherited form of intellectual disability and autism. FXS correlates with abnormal synapse and ...dendritic spine development, but the molecular link between the absence of the FMR1 product FMRP, an RNA binding protein, and the neuropathology is unclear. We found that the messenger RNA encoding bone morphogenetic protein type II receptor (BMPR2) is a target of FMRP. Depletion of FMRP increased BMPR2 abundance, especially that of the full-length isoform that bound and activated LIM domain kinase 1 (LIMK1), a component of the noncanonical BMP signal transduction pathway that stimulates actin reorganization to promote neurite outgrowth and synapse formation. Heterozygosity for BMPR2 rescued the morphological abnormalities in neurons both in Drosophila and in mouse models of FXS, as did the postnatal pharmacological inhibition of LIMK1 activity. Compared with postmortem prefrontal cortex tissue from healthy subjects, the amount of full-length BMPR2 and of a marker of LIMK1 activity was increased in this brain region from FXS patients. These findings suggest that increased BMPR2 signal transduction is linked to FXS and that the BMPR2-LIMK1 pathway is a putative therapeutic target in patients with FXS and possibly other forms of autism.
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