Agriculture is expanding into regions that are affected by salinity. This review considers the energetic costs of salinity tolerance in crop plants and provides a framework for a quantitative ...assessment of costs. Different sources of energy, and modifications of root system architecture that would maximize water vs ion up take are addressed. Energy requirements for transport of salt (NaCl) to leaf vacuoles for osmotic adjustment could be small if there are no substantial leaks back across plasma membrane and tonoplast in root and leaf. The coupling ratio of the H⁺ -ATPase also is a critical component. One proposed leak, that of Na⁺ influx across the plasma membrane through certain aquaporin channels, might be coupled to water flow, thus conserving energy. For the tonoplast, control of two types of cation channels is required for energy efficiency. Transporters controlling the Na⁺ and Cl⁻ concentrations in mitochondria and chloroplasts are largely unknown and could be a major energy cost. The complexity of the system will require a sophisticated modelling approach to identify critical transporters, apoplastic barriers and root structures. This modelling approach will inform experimentation and allow a quantitative assess ment of the energy costs of Na Cl tolerance to guide breeding and engineering of molecular components.
The AMP-activated protein kinase (AMPK) is a central regulator of multiple metabolic pathways and may have therapeutic importance for treating obesity, insulin resistance, type 2 diabetes (T2D), ...non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease (CVD). Given the ubiquitous expression of AMPK, it has been a challenge to evaluate which tissue types may be most beneficially poised for mediating the positive metabolic effects of AMPK-centered treatments. In this review we evaluate the metabolic phenotypes of transgenic mouse models in which AMPK expression and function have been manipulated, and the impact this has on controlling lipid metabolism, glucose homeostasis, and inflammation. This information may be useful for guiding the development of AMPK-targeted therapeutics to treat chronic metabolic diseases.
Canagliflozin, dapagliflozin, and empagliflozin, all recently approved for treatment of type 2 diabetes, were derived from the natural product phlorizin. They reduce hyperglycemia by inhibiting ...glucose reuptake by sodium/glucose cotransporter (SGLT) 2 in the kidney, without affecting intestinal glucose uptake by SGLT1. We now report that canagliflozin also activates AMPK, an effect also seen with phloretin (the aglycone breakdown product of phlorizin), but not to any significant extent with dapagliflozin, empagliflozin, or phlorizin. AMPK activation occurred at canagliflozin concentrations measured in human plasma in clinical trials and was caused by inhibition of Complex I of the respiratory chain, leading to increases in cellular AMP or ADP. Although canagliflozin also inhibited cellular glucose uptake independently of SGLT2, this did not account for AMPK activation. Canagliflozin also inhibited lipid synthesis, an effect that was absent in AMPK knockout cells and that required phosphorylation of acetyl-CoA carboxylase (ACC) 1 and/or ACC2 at the AMPK sites. Oral administration of canagliflozin activated AMPK in mouse liver, although not in muscle, adipose tissue, or spleen. Because phosphorylation of ACC by AMPK is known to lower liver lipid content, these data suggest a potential additional benefit of canagliflozin therapy compared with other SGLT2 inhibitors.
Recently, it has been discovered that the working memory deficits induced by exposure to chronic stress can be prevented by treating stressed animals with minocycline, a putative inhibitor of ...microglial activity. One of the pressing issues that now requires clarification is exactly how exposure to chronic stress modifies microglial morphology, this being a significant issue as microglial morphology is tightly coupled with their function. To examine how chronic stress alters microglial morphology, we digitally reconstructed microglia within the rat medial prefrontal cortex. Our analysis revealed that stress increased the internal complexity of microglia, enhancing ramification (i.e. branching) without altering the overall area occupied by the cell and that this effect was more pronounced in larger cells. We subsequently determined that minocycline treatment largely abolished the pro-ramifying effects of stress. With respect to mechanisms, we could not find any evidence of increased inflammation or neurodegeneration (interleukin-1β, MHC-II, CD68, terminal deoxynucleotidyl transferase dUTP nick end labeling, and activated caspase-3). We did, however, find that chronic stress markedly increased the expression of β1-integrin (CD29), a protein previously implicated in microglial ramification. Together, these findings highlight that increased ramification of microglia may represent an important neurobiological mechanism through which microglia mediate the behavioral effects of chronic psychological stress.
To describe the outcomes of cataract surgery in the United Kingdom.
Anonymised data on 180 114 eyes from 127 685 patients undergoing cataract surgery between August 2006 and November 2010 were ...collected prospectively from 28 sites. Outcome measures included intraoperative and postoperative complication rates, and preoperative and postoperative visual acuities.
Median age at first eye surgery was 77.1 years, 36.9% cases had ocular co-pathology and 41.0% patients underwent cataract surgery on both eyes. Preoperative visual acuity was 0.30 logMAR or better in 32.0% first eyes and 47.7% second eyes. Postoperative best-measured visual acuity was 0.00 and 0.30 logMAR or better in 50.8 and 94.6% eyes without ocular co-pathology, and 32.5 and 79.9% in eyes with co-pathology. For eyes without co-pathology, postoperative uncorrected distance visual acuity was 0.00 and 0.30 logMAR or better in 27.3 and 80.9% eyes. Posterior capsule rupture or vitreous loss or both occurred in 1.95% cases, and was associated with a 42 times higher risk of retinal detachment surgery within 3 months and an eight times higher risk of endophthalmitis.
These results provide updated data for the benchmarking of cataract surgery. Visual outcomes, and the rate of posterior capsule rupture or vitreous loss or both appear stable over the past decade.
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