Neural connectivity predicts spreading of alpha-synuclein pathology in fibril-injected mouse models: Involvement of retrograde and anterograde axonal propagation.

In Parkinson's disease, some of the first alpha-synuclein aggregates appear in the olfactory system and the dorsal motor nucleus of the vagus nerve before spreading to connected brain regions. We previously demonstrated that injection of alpha-synuclein fibrils unilaterally into the olfactory bulb of wild type mice leads to widespread synucleinopathy in brain regions directly and indirectly connected to the injection site, consistently, over the course of periods longer than 6 months. Our previously reported observations support the idea that alpha-synuclein inclusions propagates between brain region through neuronal networks. In the present study, we further defined the pattern of propagation of alpha-synuclein inclusions and developed a mathematical model based on known mouse brain connectivity. Using this model, we first predicted the pattern of alpha-synuclein inclusions propagation following an injection of fibrils into the olfactory bulb. We then analyzed the fitting of these predictions to our published histological data. Our results demonstrate that the pattern of propagation we observed in vivo is consistent with axonal transport of alpha-synuclein aggregate seeds, followed by transsynaptic transmission. By contrast, simple diffusion of alpha-synuclein fits very poorly our in vivo data. We also found that the spread of alpha-synuclein inclusions appeared to primarily follow neural connections retrogradely until 9 months after injection into the olfactory bulb. Thereafter, the pattern of spreading was consistent with anterograde propagation mathematical models. Finally, we applied our mathematical model to a different, previously published, dataset involving alpha-synuclein fibril injections into the striatum, instead of the olfactory bulb. We found that the mathematical model accurately predicts the reported progressive increase in alpha-synuclein neuropathology also in that paradigm. In conclusion, our findings support that the progressive spread of alpha-synuclein inclusions after injection of protein fibrils follows neural networks in the mouse connectome

Parameters that Affect Ankle Sprains During Flight

This research combines two multi-billion-dollar industries, sports and aviation, to understand how one influences the other. Ankle sprain is the world\u27s most common injury in sports played across the globe which requires air travel to compete. Literature pertaining to parameters that would affect ankle sprains on airplanes was researched. The result of exposure to these changing parameters on ankle sprains was analyzed. Limited space, temperature, posture, nutrition and sleep were the major disadvantages for ankle sprain recovery. Testing can be performed under a controlled environment to further understand the limits of airplane conditions on ankle sprains. Data from this experimentation could be used towards effective solutions in the future. However, changes can be made in the present to assist athletes with ankle sprains during air travel. Apart from inexpensive solutions such as considering seat selection for increased natural movement and maintaining a diet, there are more dedicated solutions. An airplane such as the NIKE Athlete\u27s Plane has features aiding athletes in the prehab and rehabilitation phase solving many travel related disadvantages. These solutions could reduce risk of injury, support recovery and promote optimum athletic performance

VALUE OF NEW TECHNOLOGIES IN DAIRY FARMING: THE CASE OF ROBOTIC MILKING

The economic value of the innovation robotic milking systems (AMS) is examined for Swedish dairy operations. A mixed integer mathematical programming model, considering crops, calving distribution, seasonality and capacity constraints of the AMS system, is developed. The marginal value of increasing the capacity of the AMS unit is found to amount to 40-60% of the milk revenues per cow.Technology innovations, Dairy systems, Livestock Production/Industries, Q12,

IKKα and IKKβ Regulation of DNA Damage-Induced Cleavage of Huntingtin

Background: Proteolysis of huntingtin (Htt) plays a key role in the pathogenesis of Huntington's disease (HD). However, the environmental cues and signaling pathways that regulate Htt proteolysis are poorly understood. One stimulus may be the DNA damage that accumulates in neurons over time, and the subsequent activation of signaling pathways such as those regulated by IκB kinase (IKK), which can influence neurodegeneration in HD. Methodology/Principal Findings: We asked whether DNA damage induces the proteolysis of Htt and if activation of IKK plays a role. We report that treatment of neurons with the DNA damaging agent etoposide or γ-irradiation promotes cleavage of wild type (WT) and mutant Htt, generating N-terminal fragments of 80–90 kDa. This event requires IKKβ and is suppressed by IKKα. Elevated levels of IKKα, or inhibition of IKKβ expression by a specific small hairpin RNA (shRNA) or its activity by sodium salicylate, prevents Htt proteolysis and increases neuronal resistance to DNA damage. Moreover, IKKβ phosphorylates the anti-apoptotic protein Bcl-xL, a modification known to reduce Bcl-xL levels, and activates caspases that can cleave Htt. When IKKβ expression is blocked, etoposide treatment does not decrease Bcl-xL and activation of caspases is diminished. Similar to silencing of IKKβ, increasing the level of Bcl-xL in neurons prevents etoposide-induced caspase activation and Htt proteolysis. Conclusions/Significance: These results indicate that DNA damage triggers cleavage of Htt and identify IKKβ as a prominent regulator. Moreover, IKKβ-dependent reduction of Bcl-xL is important in this process. Thus, inhibition of IKKβ may promote neuronal survival in HD as well as other DNA damage-induced neurodegenerative disorders

Book-Buying and the Grand Tour: the Italian Books at Belton House in Lincolnshire

This article examines the Italian books in the library at Belton House in Lincolnshire, which were bought by family members in the early modern period on successive continental tours. It charts the growing prevalence of books at Belton House from its construction in the late seventeenth century and considers in detail the significance of two foreign tours: the first undertaken by Sir John Brownlow (1690–1754), later Viscount Tyrconnel, in the years 1710–11; and the second by John Cust (1779–1853), later Earl Brownlow, in the years 1801–2. As a whole, the article considers the ways in which books prepared tourists for going abroad, assisted them whilst they were in foreign countries, and helped them afterwards to recollect their travels.This is the final published version. It first appeared at http://library.oxfordjournals.org/content/16/1/51.short?rss=1

Refugee and Asylum Seeker Rights

I will approach my analysis through the lens of new social movement theory and evaluate the role of the Centre for Peace and Conflict Studies (CPACS) at the University of Sydney in this context, asking: How can CPACS successfully contribute to the existing web of collective action in pro-refugee advocacy? Furthermore, as CPACS‘ struggle in re-shaping the politics and policies of the current government is a microcosm of the pro-refugee movement‘s struggle to re-shape contemporary notions of citizenship, I will shift from a micro-evaluation of CPACS to a macro-evaluation of the pro-refugee movement as a whole in successfully challenging the existing system of citizenship and model of civic engagement in Australia

Drivers of inter-year variability of plant production and decomposers across contrasting island ecosystems

Despite the likely importance of inter-year dynamics of plant production and consumer biota for driving community- and ecosystem-level processes, very few studies have explored how and why these dynamics vary across contrasting ecosystems. We utilized a well characterized system of 30 lake islands in the boreal forest zone of northern Sweden across which soil fertility and productivity vary considerably, with larger islands being more fertile and productive than smaller ones. In this system we assessed the inter-year dynamics of several measures of plant production and the soil microbial community (primary consumers in the decomposer food web) for each of 9 years, and soil microfaunal groups (secondary and tertiary consumers) for each of 6 of those years. We found that for measures of plant production and each of the three consumer trophic levels, inter-year dynamics were strongly affected by island size. Further, many variables were strongly affected by island size (and thus bottom-up regulation by soil fertility and resources) for some years but none in others, most likely due to inter-year variation in climatic conditions. For each of the plant and microbial variables for which we had 9 years of data, we also determined the inter-year coefficient of variation (CV), an inverse measure of stability. We found that CVs of some measures of plant productivity were greater on large islands while those of other measures were greater on smaller islands; CVs of microbial variables were unresponsive to island7 size. We also found that the effects of island size on the temporal dynamics of some variables were related to inter-year variability of macroclimatic variables. As such, our results show that the inter year dynamics of both plant productivity and decomposer biota across each of three trophic levels, as well as the inter-year stability of plant productivity, differs greatly across contrasting ecosystems, with potentially important but largely overlooked implications for community and ecosystem processes