Spatial control of irreversible protein aggregation

Liquid cellular compartments spatially segregate from the cytoplasm and can regulate aberrant protein aggregation, a process linked to several medical conditions, including Alzheimer's and Parkinson's diseases. Yet the mechanisms by which these droplet-like compartments affect protein aggregation remain unknown. Here, we combine kinetic theory of protein aggregation and liquid-liquid phase separation to study the spatial control of irreversible protein aggregation in the presence of liquid compartments. We find that, even for weak interactions between the compartment constituents and the aggregating monomers, aggregates are strongly enriched inside the liquid compartment relative to the surrounding cytoplasm. We show that this enrichment is caused by a positive feedback mechanism of aggregate nucleation and growth which is mediated by a flux maintaining the phase equilibrium between the compartment and the cytoplasm. Our model predicts that the compartment volume that maximizes aggregate enrichment in the compartment is determined by the reaction orders of aggregate nucleation. The underlying mechanism of aggregate enrichment could be used to confine cytotoxic protein aggregates inside droplet-like compartments suggesting potential new avenues against aberrant protein aggregation. Our findings could also represent a common mechanism for the spatial control of irreversible chemical reactions in general

Basal metabolic rate and the mass of tissues differing in metabolic scope:Migration-related covariation between individual knots<i> Calidris canutus</i>

To examine whether variability in the basal metabolic rate (BMR) of migrant shorebirds is a function of a variably sized metabolic machinery or of temporal changes in metabolic intensities at the tissue level, BMR, body composition and activity of cytochrome-c oxidase (CCO, a marker for maximum tissue respiration) were measured in 14 captive Knots Calidris canutus islandica in late spring, during the period of mass loss after the migratory body mass peak. Although the body mass cycle of captive birds closely followed the changes of free-living conspecifics, their fat-free mass of muscles and organs was somewhat lower and their fat content higher. BMR significantly declined during mass loss, as did the fat-free dry mass. BMR was an allometric function of both body mass (exponent=0.687) and lean dry mass (exponent=1.132). Fat-free dry mass of heart sind flight muscle decreased with the loss of fat. CCO-activity was determined in heart, flight muscle, leg muscle, liver and kidney. It was highest in heart and flight muscle and low in the other tissues. CCO-activity was not correlated with total fat mass. Intraspecific migration-related variation in BMR seems better explained by variation in the mass of organs with a high metabolic scope (as indicated by high CCO-activity), than by variation in the intensity of tissue metabolism

Using Empirical Information in the Era of HIV/AIDS to Inform Mitigation and Rural Development Strategies: Selected Results from African Country Studies

Community/Rural/Urban Development, Health Economics and Policy, Downloads July 2008-March 2009: 7,

Access to Land and Poverty Reduction in Rural Zambia: Connecting the Policy Issues

Key Policy Message: - Despite having relatively low population densities, inadequate access to land is one of the major causes of rural poverty in Zambia. - The apparent paradox of inadequate access to land for many rural households in a country of low population density is partially reconciled when taking into account that economically viable arable land requires at least some degree of access to basic services, water, road infrastructure, and markets. The basic public investments to make settlement economically viable have yet been made in many areas of Zambia. - Depending of future land allocation policy, access to good quality land with a market potential may become increasingly beyond the reach of many small-scale farm households, making it more difficult to achieve a smallholder-led, pro-poor agricultural development trajectory.zambia, food security, land, policy, Agricultural and Food Policy, Community/Rural/Urban Development, Consumer/Household Economics, Food Security and Poverty, Land Economics/Use, q18, q15,

Marketing Policy Options for Consumer Price Mitigation Actions in the 2008/09 Maize Marketing Season in Zambia.

1) Maize prices are rising rapidly in 2008 and are fast approaching import parity levels. 2) Maize traders, millers and farmers all agree that Zambia will likely require imports by early 2009 in order to avoid domestic maize supply shortages. 3) Official food balance sheets appear to have underestimated the demand for maize this year. They may also have slightly overestimated the size of the 2007/08 maize crop. Hence the slow government recognition of the need for maize imports. 4) As of late September 2008, neither the Government of Zambia (GRZ) nor the private sector have arranged to import maize from South Africa. Trade sources suggest informal imports from Tanzania are helping to relieve the likely shortfall. 5) Zambian policy makers face a delicate balancing act: they need to maintain remunerative prices for farmers, in order to stimulate maize supply response during the coming 2008/09 production season, while at the same time moderating maize meal price increases to protect urban consumers and the many rural households who are net buyers of maize. 6) The time to respond to this balancing act challenge is now rather than later in the marketing season when costs of supplies and transport will increase. 7) Several policy actions offer potential win/win options for balancing these twin concerns:food security, food policy, Zambia, maize, marketing, Crop Production/Industries, Q20,

Anticipating and Responding to Drought Emergencies in Southern Africa: Lessons from the 2002-2003 Experience

This paper examines the efficiency and effectiveness of emergency response in southern Africa through the lens of the 2002/03 food crisis in the region. The authors outline improvements in information and operational procedures needed to enhance the response to future events. They also discuss national and regional trade regime changes that would reduce the need for emergency response, and consider what lessons the 2002/03 crisis may have for the role of Strategic Grain Reserves (SGRs).food security, drought, emergency, Southern Africa, Food Security and Poverty, Q18,

Enhanced potency of aggregation inhibitors mediated by liquid condensates

Liquid condensates are membraneless organelles that form via phase separation in living cells. These condensates provide unique heterogeneous environments that have much potential in regulating a range of biochemical processes from gene expression to filamentous protein aggregation—a process linked to Alzheimer's and Parkinson's diseases. Here we theoretically study the physical interplay between protein aggregation, its inhibition, and liquid-liquid phase separation. Our key finding is that the action of protein aggregation inhibitors can be strongly enhanced by liquid condensates. The physical mechanism of this enhancement relies on the partitioning and colocalization of inhibitors with their targets inside the liquid condensate. Our theory uncovers how the physicochemical properties of condensates can be used to modulate inhibitor potency, and we provide experimentally testable conditions under which drug potency is maximal. Our findings suggest design principles for protein aggregation inhibitors with respect to their phase-separation properties

Aggregation controlled by condensate rheology

Biomolecular condensates in living cells can exhibit a complex rheology, including viscoelastic and glassy behavior. This rheological behavior of condensates was suggested to regulate polymerization of cytoskeletal filaments and aggregation of amyloid fibrils. Here, we theoretically investigate how the rheological properties of condensates can control the formation of linear aggregates. To this end, we propose a kinetic theory for linear aggregation in coexisting phases, which accounts for the aggregate size distribution and the exchange of aggregates between inside and outside of condensates. The rheology of condensates is accounted in our model via aggregate mobilities that depend on aggregate size. We show that condensate rheology determines whether aggregates of all sizes or dominantly small aggregates are exchanged between condensate inside and outside on the timescale of aggregation. As a result, the ratio of aggregate numbers inside to outside of condensates differs significantly. Strikingly, we also find that weak variations in the rheological properties of condensates can lead to a switch-like change of the number of aggregates. These results suggest a possible physical mechanism for how living cells could control linear aggregation in a switch-like fashion through variations in condensate rheology

Towards a Strategy for Improving Agricultural Inputs Markets in Africa

Agribusiness, Downloads July 2008-July 2009: 19,