Synesthesia, transformation and synthesis : toward a multi-sensory pedagogy of the image

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Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Heme binding induces dimerization and nitration of truncated β-amyloid peptide Aβ16 under oxidative stress.

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Homeostatic response to hypoxia is regulated by the N-end rule pathway in plants

Plants and animals are obligate aerobes, requiring oxygen for mitochondrial respiration and energy production. In plants, an unanticipated decline in oxygen availability (hypoxia), as caused by roots becoming waterlogged or foliage submergence, triggers changes in gene transcription and messenger RNA translation that promote anaerobic metabolism and thus sustain substrate-level ATP production1. In contrast to animals2, oxygen sensing has not been ascribed to a mechanism of gene regulation in response to oxygen deprivation in plants. Here we show that the N-end rule pathway of targeted proteolysis acts as a homeostatic sensor of severe low oxygen levels in Arabidopsis, through its regulation of key hypoxia-response transcription factors. We found that plants lacking components of the N-end rule pathway constitutively express core hypoxia-response genes and are more tolerant of hypoxic stress. We identify the hypoxia-associated ethylene response factor group VII transcription factors of Arabidopsis as substrates of this pathway. Regulation of these proteins by the N-end rule pathway occurs through a characteristic conserved motif at the amino terminus initiating with Met-Cys. Enhanced stability of one of these proteins, HRE2, under low oxygen conditions improves hypoxia survival and reveals a molecular mechanism for oxygen sensing in plants via the evolutionarily conserved N-end rule pathway. SUB1A-1, a major determinant of submergence tolerance in rice3, was shown not to be a substrate for the N-end rule pathway despite containing the N-terminal motif, indicating that it is uncoupled from N-end rule pathway regulation, and that enhanced stability may relate to the superior tolerance of Sub1 rice varieties to multiple abiotic stresses4

FeNC oxygen reduction electrocatalyst with high utilisation penta‐coordinated sites

International audienceAtomic Fe in N-doped carbon (FeNC) electrocatalysts for oxygen (O$_2$) reduction at the cathode of proton exchange membrane fuel cells (PEMFCs) are the most promising alternative to platinum-group-metal catalysts. Despite recent progress on atomic FeNC O$_2$ reduction, their controlled synthesis and stability for practical applications remains challenging. A two-step synthesis approach has recently led to significant advances in terms of Fe-loading and mass activity; however, the Fe utilisation remains low owing to the difficulty of building scaffolds with sufficient porosity that electrochemically exposes the active sites. Herein, we addressed this issue by coordinating Fe in a highly porous nitrogen doped carbon support (~3295 m$^2$ g$^{-1}$), prepared by pyrolysis of inexpensive 2,4,6triaminopyrimidine and a Mg$^{2+}$ salt active site template and porogen. Upon Fe coordination, a high electrochemical active site density of 2.54×10$^{19}$ sites g$_{FeNC}$$^{-1}$ and a record 52% FeN$_x$ electrochemical utilisation based on in situ nitrite stripping was achieved. The Fe single atoms are characterised pre-and post-electrochemical accelerated stress testing by aberration-corrected high-angle annular dark field scanning transmission electron microscopy, showing no Fe clustering. Moreover, ex situ X-ray absorption spectroscopy and low-temperature Mössbauer spectroscopy suggest the presence of penta-coordinated Fe sites, which were further studied by density functional theory calculations

FeNC oxygen reduction electrocatalyst with high utilisation penta‐coordinated sites

International audienceAtomic Fe in N-doped carbon (FeNC) electrocatalysts for oxygen (O$_2$) reduction at the cathode of proton exchange membrane fuel cells (PEMFCs) are the most promising alternative to platinum-group-metal catalysts. Despite recent progress on atomic FeNC O$_2$ reduction, their controlled synthesis and stability for practical applications remains challenging. A two-step synthesis approach has recently led to significant advances in terms of Fe-loading and mass activity; however, the Fe utilisation remains low owing to the difficulty of building scaffolds with sufficient porosity that electrochemically exposes the active sites. Herein, we addressed this issue by coordinating Fe in a highly porous nitrogen doped carbon support (~3295 m$^2$ g$^{-1}$), prepared by pyrolysis of inexpensive 2,4,6triaminopyrimidine and a Mg$^{2+}$ salt active site template and porogen. Upon Fe coordination, a high electrochemical active site density of 2.54×10$^{19}$ sites g$_{FeNC}$$^{-1}$ and a record 52% FeN$_x$ electrochemical utilisation based on in situ nitrite stripping was achieved. The Fe single atoms are characterised pre-and post-electrochemical accelerated stress testing by aberration-corrected high-angle annular dark field scanning transmission electron microscopy, showing no Fe clustering. Moreover, ex situ X-ray absorption spectroscopy and low-temperature Mössbauer spectroscopy suggest the presence of penta-coordinated Fe sites, which were further studied by density functional theory calculations

FeNC oxygen reduction electrocatalyst with high utilisation penta‐coordinated sites

International audienceAtomic Fe in N-doped carbon (FeNC) electrocatalysts for oxygen (O$_2$) reduction at the cathode of proton exchange membrane fuel cells (PEMFCs) are the most promising alternative to platinum-group-metal catalysts. Despite recent progress on atomic FeNC O$_2$ reduction, their controlled synthesis and stability for practical applications remains challenging. A two-step synthesis approach has recently led to significant advances in terms of Fe-loading and mass activity; however, the Fe utilisation remains low owing to the difficulty of building scaffolds with sufficient porosity that electrochemically exposes the active sites. Herein, we addressed this issue by coordinating Fe in a highly porous nitrogen doped carbon support (~3295 m$^2$ g$^{-1}$), prepared by pyrolysis of inexpensive 2,4,6triaminopyrimidine and a Mg$^{2+}$ salt active site template and porogen. Upon Fe coordination, a high electrochemical active site density of 2.54×10$^{19}$ sites g$_{FeNC}$$^{-1}$ and a record 52% FeN$_x$ electrochemical utilisation based on in situ nitrite stripping was achieved. The Fe single atoms are characterised pre-and post-electrochemical accelerated stress testing by aberration-corrected high-angle annular dark field scanning transmission electron microscopy, showing no Fe clustering. Moreover, ex situ X-ray absorption spectroscopy and low-temperature Mössbauer spectroscopy suggest the presence of penta-coordinated Fe sites, which were further studied by density functional theory calculations