Changes in insulin and insulin signaling in Alzheimer\u27s disease: Cause or consequence?

Individuals with type 2 diabetes have an increased risk for developing Alzheimer’s disease (AD), although the causal relationship remains poorly understood. Alterations in insulin signaling (IS) are reported in the AD brain. Moreover, oligomers/fibrils of amyloid-β (Aβ) can lead to neuronal insulin resistance and intranasal insulin is being explored as a potential therapy for AD. Conversely, elevated insulin levels (ins) are found in AD patients and high insulin has been reported to increase Aβ levels and tau phosphorylation, which could exacerbate AD pathology. Herein, we explore whether changes in ins and IS are a cause or consequence of AD

State Legislative Update

As the use of collaborative law increases, the need for uniform laws to help facilitate this process across state lines grew. In February 2007, the Uniform Law Commission (ULC) began drafting an act to address this need. At the July 2009 meeting, the Uniform Collaborative Law Act (UCLA) was unanimously approved by the Commission and was subsequently submitted to the American Bar Association (ABA) House of Delegates for approval. In March 2010, the house approved the amended act after the ULC made a few small changes per the house\u27s recommendation. Since receiving ABA approval, the UCLA has been passed in eight states, most recently Alabama, and introduced this year in five more

The effects of peripheral and central high insulin on brain insulin signaling and amyloid-β in young and old APP/PS1 mice

Hyperinsulinemia is a risk factor for late-onset Alzheimer's disease (AD). In vitro experiments describe potential connections between insulin, insulin signaling, and amyloid-β (Aβ), but in vivo experiments are needed to validate these relationships under physiological conditions. First, we performed hyperinsulinemic-euglycemic clamps with concurrent hippocampal microdialysis in young, awake, behaving APP(swe)/PS1(dE9) transgenic mice. Both a postprandial and supraphysiological insulin clamp significantly increased interstitial fluid (ISF) and plasma Aβ compared with controls. We could detect no increase in brain, ISF, or CSF insulin or brain insulin signaling in response to peripheral hyperinsulinemia, despite detecting increased signaling in the muscle. Next, we delivered insulin directly into the hippocampus of young APP/PS1 mice via reverse microdialysis. Brain tissue insulin and insulin signaling was dose-dependently increased, but ISF Aβ was unchanged by central insulin administration. Finally, to determine whether peripheral and central high insulin has differential effects in the presence of significant amyloid pathology, we repeated these experiments in older APP/PS1 mice with significant amyloid plaque burden. Postprandial insulin clamps increased ISF and plasma Aβ, whereas direct delivery of insulin to the hippocampus significantly increased tissue insulin and insulin signaling, with no effect on Aβ in old mice. These results suggest that the brain is still responsive to insulin in the presence of amyloid pathology but increased insulin signaling does not acutely modulate Aβ in vivo before or after the onset of amyloid pathology. Peripheral hyperinsulinemia modestly increases ISF and plasma Aβ in young and old mice, independent of neuronal insulin signaling. SIGNIFICANCE STATEMENT The transportation of insulin from blood to brain is a saturable process relevant to understanding the link between hyperinsulinemia and AD. In vitro experiments have found direct connections between high insulin and extracellular Aβ, but these mechanisms presume that peripheral high insulin elevates brain insulin significantly. We found that physiological hyperinsulinemia in awake, behaving mice does not increase CNS insulin to an appreciable level yet modestly increases extracellular Aβ. We also found that the brain of aged APP/PS1 mice was not insulin resistant, contrary to the current state of the literature. These results further elucidate the relationship between insulin, the brain, and AD and its conflicting roles as both a risk factor and potential treatment

State of the Forest Carbon Markets 2012

Over the last three years, projects that address the relationships between carbon and forests have moved from the sidelines of international climate action to center field. Forestry’s recent advancements are the product of decades of ongoing collaboration among market and environmental experts seeking to strike an ideal balance between forestry projects’ market risks and shared benefits. Market dynamics in 2011 demonstrated that these efforts have never been more pivotal, or complex, as forest carbon projects mature – and find themselves positioned squarely in the midst of some of today’s most challenging policy debates. This year, a record number of forest project developers and secondary market suppliers from around the world shared data about their projects and transactions. This third annual State of the Forest Carbon Markets tracks, reports, and analyzes trends in these responses. This information is primarily based on data collected from respondents to Ecosystem Marketplace’s 2011 forest carbon project developer’s survey, combined with data from the 2012 State of the Voluntary Carbon Markets report. The data and analysis that follow cover forest carbon activity in compliance carbon markets – including the Kyoto Protocol’s Clean Development Mechanism (CDM), the New Zealand Emissions Trading Scheme (NZ ETS), the New South Wales Greenhouse Gas Reduction Scheme (NSW GGAS) and British Columbia’s (BC) Carbon Neutral Government directive – as well as voluntary carbon markets including voluntary Over-the-Counter (OTC) market and country-specific voluntary programs worldwide. In total, we captured responses from 140 project developers or project proponents in the primary forest carbon market and 35 suppliers in the secondary market. Respondents represented 215 individual forest carbon projects, half of which transacted credits in 2011 – totaling 451 projects analyzed in all survey years

KATP channels are necessary for glucose-dependent increases in amyloid-β and Alzheimer\u27s disease-related pathology

Elevated blood glucose levels, or hyperglycemia, can increase brain excitability and amyloid-β (Aβ) release, offering a mechanistic link between type 2 diabetes and Alzheimer\u27s disease (AD). Since the cellular mechanisms governing this relationship are poorly understood, we explored whether ATP-sensitive potassium (KATP) channels, which couple changes in energy availability with cellular excitability, play a role in AD pathogenesis. First, we demonstrate that KATP channel subunits Kir6.2/KCNJ11 and SUR1/ABCC8 were expressed on excitatory and inhibitory neurons in the human brain, and cortical expression of KCNJ11 and ABCC8 changed with AD pathology in humans and mice. Next, we explored whether eliminating neuronal KATP channel activity uncoupled the relationship between metabolism, excitability, and Aβ pathology in a potentially novel mouse model of cerebral amyloidosis and neuronal KATP channel ablation (i.e., amyloid precursor protein [APP]/PS1 Kir6.2-/- mouse). Using both acute and chronic paradigms, we demonstrate that Kir6.2-KATP channels are metabolic sensors that regulate hyperglycemia-dependent increases in interstitial fluid levels of Aβ, amyloidogenic processing of APP, and amyloid plaque formation, which may be dependent on lactate release. These studies identify a potentially new role for Kir6.2-KATP channels in AD and suggest that pharmacological manipulation of Kir6.2-KATP channels holds therapeutic promise in reducing Aβ pathology in patients with diabetes or prediabetes

Overview of NASA Technology Development for In-Situ Resource Utilization (ISRU)

In-Situ Resource Utilization (ISRU) encompasses a broad range of systems that enable the production and use of extraterrestrial resources in support of future exploration missions. It has the potential to greatly reduce the dependency on resources transported from Earth (e.g., propellants, life support consumables), thereby significantly improving the ability to conduct future missions. Recognizing the critical importance of ISRU for the future, NASA is currently conducting technology development projects in two of its four mission directorates. The Advanced Exploration Systems Division in the Agency's Human Exploration and Operations Mission Directorate has initiated a new project for ISRU Technology focused on component, subsystem, and system maturation in the areas of water volatiles resource acquisition, and water volatiles and atmospheric processing into propellants and other consumable products. The Space Technology Mission Directorate is supporting development of ISRU component technologies in the areas of Mars atmosphere acquisition, including dust management, and oxygen production from Mars atmosphere for propellant and life support consumables. Together, these two coordinated projects are working towards a common goal of demonstrating ISRU technology and systems in preparation for future flight applications

Hyperglycemia modulates extracellular amyloid-β concentrations and neuronal activity in vivo

Epidemiological studies show that patients with type 2 diabetes (T2DM) and individuals with a diabetes-independent elevation in blood glucose have an increased risk for developing dementia, specifically dementia due to Alzheimer’s disease (AD). These observations suggest that abnormal glucose metabolism likely plays a role in some aspects of AD pathogenesis, leading us to investigate the link between aberrant glucose metabolism, T2DM, and AD in murine models. Here, we combined two techniques — glucose clamps and in vivo microdialysis — as a means to dynamically modulate blood glucose levels in awake, freely moving mice while measuring real-time changes in amyloid-β (Aβ), glucose, and lactate within the hippocampal interstitial fluid (ISF). In a murine model of AD, induction of acute hyperglycemia in young animals increased ISF Aβ production and ISF lactate, which serves as a marker of neuronal activity. These effects were exacerbated in aged AD mice with marked Aβ plaque pathology. Inward rectifying, ATP-sensitive potassium (K(ATP)) channels mediated the response to elevated glucose levels, as pharmacological manipulation of K(ATP) channels in the hippocampus altered both ISF Aβ levels and neuronal activity. Taken together, these results suggest that K(ATP) channel activation mediates the response of hippocampal neurons to hyperglycemia by coupling metabolism with neuronal activity and ISF Aβ levels

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes