A eta-alpha and A eta-beta peptides impair LTP ex vivo within the low nanomolar range and impact neuronal activity in vivo

Background: Amyloid precursor protein (APP) processing is central to Alzheimer’s disease (AD) etiology. As early cognitive alterations in AD are strongly correlated to abnormal information processing due to increasing synaptic impairment, it is crucial to characterize how peptides generated through APP cleavage modulate synapse function. We previously described a novel APP processing pathway producing η-secretase-derived peptides (Aη) and revealed that Aη–α, the longest form of Aη produced by η-secretase and α-secretase cleavage, impaired hippocampal long-term potentiation (LTP) ex vivo and neuronal activity in vivo. Methods: With the intention of going beyond this initial observation, we performed a comprehensive analysis to further characterize the effects of both Aη-α and the shorter Aη-β peptide on hippocampus function using ex vivo field electrophysiology, in vivo multiphoton calcium imaging, and in vivo electrophysiology. Results: We demonstrate that both synthetic peptides acutely impair LTP at low nanomolar concentrations ex vivo and reveal the N-terminus to be a primary site of activity. We further show that Aη-β, like Aη–α, inhibits neuronal activity in vivo and provide confirmation of LTP impairment by Aη–α in vivo. Conclusions: These results provide novel insights into the functional role of the recently discovered η-secretase-derived products and suggest that Aη peptides represent important, pathophysiologically relevant, modulators of hippocampal network activity, with profound implications for APP-targeting therapeutic strategies in AD

The normalisation of Food Aid: What happened to feeding people well?

In the UK, food poverty has increased in the last 15 years and the food aid supply chain that has emerged to tackle it is now roughly 10 years old. In this time, we have seen the food aid supply chain grow at a rate that has astounded many.  Recently that growth has been aided by a grant of £20m from a large supermarket chain. It appears institutionalisation is just around the corner, if not already here. It also appears that there is far greater emphasis on dealing with  the symptoms as opposed to solving the root causes of the problem. As an opinion piece, this paper reflects on some of the prevalent issues, and suggests some ways forward

Underground testing : name-altering practices as probes in electronic music

Name-altering practices are common in many creative fields – pen names in literature, stage names in the performing arts, aliases in music. More than just reflecting artistic habits or responding to the need for distinctive brands, these practices can also serve as test devices to probe, validate, and guide the artists’ active participation in a cultural movement. At the same time, they constitute a powerful probe to negotiate the boundaries of a subculture, especially when its features are threatened by appropriation from the mass-oriented culture. Drawing evidence from electronic music, a field where name-altering practices proliferate, we outline dynamics of pseudonymity, polyonymy, and anonymity that surround the use of aliases. We argue that name-altering practices are both a tool artists use to probe the creative environment and a device to recursively put one’s creative participation to the test. In the context of creative subcultures, name-altering practices constitute a subtle but effective form of underground testing

Heartbreak Hotei: Spirituality and Metabolic Syndrome

James, Christine (2013). Heartbreak Hotei: Spirituality and Metabolic Syndrome. Chronic Illness, Spirituality, and Healing. 1 electronic record (PDF).Colloquially, the medical diagnosis of “metabolic syndrome” and the physical condition of obesity might not be understood as chronic illness or chronic disease. To the lay person, chronic illness often refers to something “out of the patient’s control.” In contrast, chronic illness such as Crohn’s disease and celiac disease are not usually thought to be the result of repeated, habitual, poor dietary choices on the part of the patient; this is even less so with chronic conditions like multiple sclerosis or cystic fibrosis. Metabolic syndrome is not necessarily considered a chronic condition, because it can be remediated through lifestyle changes, healthier choices in food intake, and physical activity. Nevertheless, metabolic syndrome is directly related to chronic illness in terms of a specific set of clinical outcomes that are recognized by the Centers for Disease Control as chronic diseases, among them “heart disease, stroke, cancer, diabetes, and arthritis” (CDC, 2012). These chronic diseases are often listed in the medical diagnostic literature as clinical outcomes of metabolic syndrome, “a condition characterized by multiple risk factors” (AHA, 2004). The Mayo Clinic defines metabolic syndrome as a cluster of conditions—increased blood pressure, a high blood sugar level, excess body fat around the waist or abnormal cholesterol levels—that occur together, increasing your risk of heart disease, stroke and diabetes. Having just one of these conditions doesn’t mean you have metabolic syndrome. However, any of these conditions increase your risk of serious disease. (Mayo Clinic, 2011