Social and Behavioral Sciences Commons^™

The Dissociated Form Of Kappa-Casein Is The Precursor To Its Amyloid Fibril Formation, Heath Ecroyd, David Thorn, Yanqin Liu, John Carver

Heath Ecroyd

Bovine milk kappa-casein forms a self-associating oligomeric micelle-like species, in equilibrium with dissociated forms. In its native form, intra- and inter-molecular disulfide bonds lead to the formation of multimeric species ranging from monomers to decamers. When incubated under conditions of physiological pH and temperature, both reduced and non-reduced kappa-casein form highly structured beta-sheet amyloid fibrils. We investigated whether the precursor to kappa-casein fibril formation is a dissociated state of the protein or its oligomeric micelle-like form. We show that reduced kappa-casein is capable of forming fibrils well below its critical micelle concentration, i.e. at concentrations where only dissociated forms of …

The Interaction Of Unfolding Α-Lactalbumin And Malate Dehydrogenase With The Molecular Chaperone Αb-Crystallin: A Light And X-Ray Scattering Investigation, J W. Regini, Heath Ecroyd, Sarah Meehan, Kristen Bremmell, Matthew J. Clarke, Donna Lammie, Tim Wess, John A. Carver

Heath Ecroyd

Purpose: The molecular chaperone αB-crystallin is found in high concentrations in the lens and is present in all major body tissues. Its structure and the mechanism by which it protects its target protein from aggregating and precipitating are not known. Methods: Dynamic light scattering and X-ray solution scattering techniques were used to investigate structural features of the αB-crystallin oligomer when complexed with target proteins under mild stress conditions, i.e., reduction of α- lactalbumin at 37 °C and malate dehydrogenase when heated at 42 °C. In this investigation, the size, shape and particle distribution of the complexes were determined in real-time …

(-)-Epigallocatechin-3-Gallate (Egcg) Maintains K-Casein In Its Pre-Fibrillar State Without Redirecting Its Aggregation Pathway, Sean A. Hudson, Heath Ecroyd, Francis C. Dehle, Ian F. Musgrave, John Carver

Heath Ecroyd

The polyphenol (-)-epigallocatechin-3-gallate (EGCG) has recently attracted much research interest in the field of protein-misfolding diseases because of its potent anti-amyloid activity against amyloid-beta, alpha-synuclein and huntingtin, the amyloid-fibril-forming proteins involved in Alzheimer's, Parkinson's and Huntington's diseases, respectively. EGCG redirects the aggregation of these polypeptides to a disordered off-folding pathway that results in the formation of non-toxic amorphous aggregates. whether this anti-fibril activity is specific to these disease-related target proteins or ismore generic remains to be established. In addition, the mechanism by which EGCG exerts its effects, as with all anti-amyloidogenic polyphenols, remains unclear. To address these aspects, we have …

New Proteins Identified In Epididymal Fluid From The Platypus (Ornithorhynchus Anatinus), Jean-Louis Dacheux, Francoise Dacheux, Valerie Labas, Heath Ecroyd, Brett Nixon, Russell C. Jones

Heath Ecroyd

The platypus epididymal proteome is being studied because epididymal proteins are essential for male fertility in mammals and it is considered that knowledge of the epididymal proteome in an early mammal would be informative in assessing the convergence and divergence of proteins that are important in the function of the mammalian epididymis. Few of the epididymal proteins that have been identified in eutherian mammals were found in platypus caudal epididymal fluid, and the major epididymal proteins in the platypus (PXN-FBPL, SPARC and E-OR20) have never been identified in the epididymis of any other mammal.

Mimicking Phosphorylation Of Alphab-Crystallin Affects Its Chaperone Activity, Heath W. Ecroyd, Sarah Meehan, J Horwitz, Andrew Aquilina, J L Benesch, C V Robinson, Cait Macphee, John Carver

Heath Ecroyd

No abstract provided.

The Thioflavin T Fluorescence Assay For Amyloid Fibril Detection Can Be Biased By The Presence Of Exogenous Compounds, Sean A. Hudson, Heath Ecroyd, Tak W. Kee, John A. Carver

Heath Ecroyd

Thioflavin T (ThT) dye fluorescence is used regularly to quantify the formation and inhibition of amyloid fibrils in the presence of anti-amyloidogenic compounds such as polyphenols. However, in this study, it was shown, using three polyphenolics (curcumin, quercetin and resveratrol), that ThT fluorescence should be used with caution in the presence of such exogenous compounds. The strong absorptive and fluorescent properties of quercetin and curcumin were found to significantly bias the ThT fluorescence readings in both in situ real-time ThT assays and single time-point dilution ThT-type assays. The presence of curcumin at concentrations as low as 0.01 and 1 uM …

Unraveling The Mysteries Of Protein Folding And Misfolding, Heath Ecroyd, John A. Carver

Heath Ecroyd

This mini-review focuses on the processes and consequences of protein folding and misfolding. The latter process often leads to protein aggregation and precipitation with the aggregates adopting either highly ordered (amyloid fibril) or disordered (amorphous) forms. In particular, the amyloid fibril is discussed because this form has gained considerable notoriety due to its close links to a variety of debilitating diseases including Alzheimer's, Parkinson's, Huntington's, and Creutzfeldt-Jakob diseases, and type-II diabetes. In each of these diseases a different protein forms fibrils, yet the fibrils formed have a very similar structure. The mechanism by which fibrils form, fibril structure, and the …

Crystallin Proteins And Amyloid Fibrils, Heath Ecroyd, John A. Carver

Heath Ecroyd

Improper protein folding (misfolding) can lead to the formation of disordered (amorphous) or ordered (amyloid fibril) aggregates. The major lens protein, alpha-crystallin, is a member of the small heat-shock protein (sHsp) family of intracellular molecular chaperone proteins that prevent protein aggregation. Whilst the chaperone activity of sHsps against amorphously aggregating proteins has been well studied, its action against fibril-forming proteins has received less attention despite the presence of sHsps in deposits found in fibril-associated diseases (e.g. Alzheimer's and Parkinson's). In this review, the literature on the interaction of alpha B-crystallin and other sHsps with fibril-forming proteins is summarized. In particular, …

Alphab-Crystallin Inhibits The Cell Toxicity Associated With Amyloid Fibril Formation By Kappa-Casein And The Amyloid-Beta Peptide, Francis C. Dehle, Heath Ecroyd, Ian F. Musgrave, John A. Carver

Heath Ecroyd

Amyloid fibril formation is associated with diseases such as Alzheimer’s, Parkinson’s, and prion diseases. Inhibition of amyloid fibril formation by molecular chaperone proteins, such as the small heat-shock protein αB-crystallin, may play a protective role in preventing the toxicity associated with this form of protein misfolding. Reduced and carboxymethylated κ-casein (RCMκ-CN), a protein derived from milk, readily and reproducibly forms fibrils at physiological temperature and pH. We investigated the toxicity of fibril formation by RCMκ-CN using neuronal model PC12 cells and determined whether the inhibition of fibril formation altered its cell toxicity. To resolve ambiguities in the literature, we also …

The Epididymal Soluble Prion Protein Forms A High-Molecular-Mass Complex In Association With Hydrophobic Proteins, Heath W. Ecroyd, Maya Belghazi, Jean-Louis Dacheux, Jean-Luc Gatti

Heath Ecroyd

We have shown previously that a 'soluble' form of PrP (prion protein), not associated with membranous vesicles, exists in the male reproductive fluid [Ecroyd, Sarradin, Dacheux and Gatti (2004) Biol. Reprod. 71, 993-1001]. Attempts to purify this 'soluble' PrP indicated that it behaves like a high-molecular-mass complex of more than 350 kDa and always co-purified with the same set of proteins. The main associated proteins were sequenced by MS and were found to match to clusterin (apolipoprotein J), BPI (bacterial permeability-increasing protein), carboxylesterase-like urinary excreted protein (cauxin), beta-mannosidase and beta-galactosidase. Immunoblotting and enzymatic assay confirmed the presence of clusterin and …

Compartmentalization Of Prion Isoforms Within The Reproductive Tract Of The Ram, Heath W. Ecroyd, Pierre Sarradin, Jean-Louis Dacheux, Jean-Luc Gatti

Heath Ecroyd

Cellular prion protein (Prp(C)) is a glycoprotein usually associated with membranes via its glycosylphosphatidylinositol (GPI) anchor. The trans-conformational form of this protein (Prp(SC)) is the suggested agent responsible for transmissible neurodegenerative spongiform encephalopathies. This protein has been shown on sperm and in the reproductive fluids of males. Antibodies directed against the C-terminal sequence near the GPI-anchor site, an N-terminal sequence, and against the whole protein showed that the Prp isoforms were compartmentalized within the reproductive tract of the ram. Immunoblotting with the three antibodies showed that the complete protein and both N- and C-terminally truncated and glycosylated isoforms are present …

Site-Directed Mutations In The C-Terminal Extension Of Human Αb-Crystallin Affect Chaperone Function And Block Amyloid Fibril Formation, T. M. Treweek, Heath Ecroyd, D. M. Williams, S. Meehan, J. A. Carver, M. J. Walker

Heath Ecroyd

Alzheimer’s, Parkinson’s and Creutzfeldt-Jakob disease are associated with inappropriate protein deposition and ordered amyloid fibril assembly. Molecular chaperones, including αBcrystallin, play a role in the prevention of protein deposition. A series of site-directed mutants of the human molecular chaperone, αB-crystallin, were constructed which focused on the flexible C-terminal extension of the protein. We investigated the structural role of this region as well as its role in the chaperone function of αB-crystallin under different types of protein aggregation, i.e. disordered amorphous aggregation and ordered amyloid fibril assembly. It was found that mutation of lysine and glutamic acid residues in the C-terminal …

Small Heat-Shock Proteins Interact With A Flanking Domain To Suppress Polyglutamine Aggregation, Amy L. Roberston, Stephen J. Headey, Helen M. Saunders, Heath Ecroyd, Martin J. Scanlon, John A. Carver, Stephen P. Bottomley

Heath Ecroyd

Small heat-shock proteins (sHsps) are molecular chaperones that play an important protective role against cellular protein misfolding by interacting with partially unfolded proteins on their off-folding pathway, preventing their aggregation. Polyglutamine (polyQ) repeat expansion leads to the formation of fibrillar protein aggregates and neuronal cell death in nine diseases, including Huntington disease and the spinocerebellar ataxias (SCAs). There is evidence that sHsps have a role in suppression of polyQ-induced neurodegeneration; for example, the sHsp alphaB-crystallin (αB-c) has been identified as a suppressor of SCA3 toxicity in a Drosophila model. However, the molecular mechanism for this suppression is unknown. In this …

The Development Of Signal Transduction Pathways During Epididymal Maturation Is Calcium Dependent, Heath W. Ecroyd, Kelly Asquith, Russell C. Jones, Robert J. Aitken

Heath Ecroyd

Capacitation has been correlated with the activation of a cAMP-PKA-dependent signaling pathway leading to protein tyrosine phosphorylation. The ability to exhibit this response to cAMP matures during epididymal maturation in concert with the ability of the sperrnatozoa to capacitate. In this study, we have addressed the mechanisms by which spermatozoa gain the potential to activate this signaling pathway during epididymal maturation. In a modified Tyrode's medium containing 1.7 mM calcium, caput spermatozoa had significantly higher [Ca2+](i) than caudal cells and could not tyrosine phosphorylate in response to cAMP. However, in calcium-depleted medium both caput and caudal cells could exhibit a …

The Interaction Of Alphab-Crystallin With Mature Alpha-Synuclein Amyloid Fibrils Inhibits Their Elongation, Christopher A. Waudby, Tuomas P. J Knowles, Glyn L. Devlin, Jeremy N. Skepper, Heath Ecroyd, John A. Carver, Mark E. Welland, John Christodoulou, Christopher M. Dobson, Sarah Meehan

Heath Ecroyd

alphaB-Crystallin is a small heat-shock protein (sHsp) that is colocalized with alpha-synuclein (alphaSyn) in Lewy bodies—the pathological hallmarks of Parkinson's disease—and is an inhibitor of alphaSyn amyloid fibril formation in an ATP-independent manner in vitro. We have investigated the mechanism underlying the inhibitory action of sHsps, and here we establish, by means of a variety of biophysical techniques including immunogold labeling and nuclear magnetic resonance spectroscopy, that alphaB-crystallin interacts with alphaSyn, binding along the length of mature amyloid fibrils. By measurement of seeded fibril elongation kinetics, both in solution and on a surface using a quartz crystal microbalance, this binding …

Grassroots Democracy And Non-State Approaches Toward Popular Empowerment And Rural Sustainbility In The Philippines = 菲律賓的草根民主實戰, Eduardo Tadem

South South Forum 南南論壇

Grassroots democracy is often equated with “popular participation” and is seen as both a goal and a method of change. As Kaufman (1997: 7) puts it:

As a goal, popular participation refers to a society where there no longer exists a monopoly of the means of political, economic, cultural, and social power in the hands of a particular class, sex, social stratum, or bureaucratic elite. As a method of change, participation is a means to develop the voice and organizational capacity of those previously excluded; it is a means for the majority of the population to identify and express their …

Decentralization And Local Participatory Development : Experiences From Cambodia And The Philippines = 去中心化與本土參與式發展 : 以柬埔寨與菲律賓為例, Maria Dolores Alicias

South South Forum 南南論壇

No abstract provided.

Participatory Approach In Rural Poverty-Alleviation And Women's Empowerment In Indonesia = 印度尼西亞參與式農村扶貧與婦女賦權計劃, Mayling Oey-Gardiner

South South Forum 南南論壇

Indonesian Society – In spite of the general observation that women in Indonesia remain subordinate to men in the public domain, due to development efforts promoting participatory approaches and women’s empowerment in Indonesia’s democratizing society there have been some notable success stories of women-led economic activities and of women reaching high positions in their communities and the wider society as well. Here, one result of the Asian financial-turned economic crisis which started in Indonesia in mid-1997 was a period of severe socio-economic-political turmoil (a situation known locally as kristal for total crisis) leading to a revitalized democratic movement, giving greater …

Solidarity Economy And Alternative Currency In Latin America = 中美洲互助經濟與另類貨幣, Maria Eugenia Santana

South South Forum 南南論壇

From the very beginning of the millennium the call of the World Social Forum has gathered each year thousands of social organizations and movements of all kinds imaginable under the motto “Another world is possible!”. This way tens of thousands civil organizations gather in search of alternatives to the current world, to the current system, to the current way of life.

This need of Another World –better yet: of Other Worlds- is the certainty of the depletion of the hegemonic neoliberal system: if more than half of the world population is suffering of hunger and sickness this is due to …

The Global Crisis As A Global Opportunity : The Barcelona Consensus Process = 全球危機作為全球機會 : 巴塞羅那共識, Marti Olivella

South South Forum 南南論壇

The global crisis demands global answers; answers that cannot come from those who provoked, accepted or took advantage of its causes.

The world architecture built upon the ashes of the World War II is collapsing. The great foundations that granted America its hegemony, shared in part with all the other winners, 64 years later can no longer answer the necessities of a world undergoing deep transformations of various kinds. Neither Bretton Woods (America's pillar in the economic-financial network in the IMF and the WB) nor the UN (political pillar in the Security Council) or the atom bomb(military pillar), which sealed …

African Economy And Land Policy, Ebrima Sall

South South Forum 南南論壇

Thandika Mkandawire reminded us during the 13th CODESRIA GA that land and the agrarian question were present in some way in all the nationalist movements, and liberation struggles the Mau Mau in Kenya, the FLN’s struggles in Algeria, the PAIGC in Guinea Bissau, other struggles in Zimbabwe, South Africa, etc. We know that apartheid South Africa was the story of dispossession—(Pheko)—the reverse
movement in South Africa—re-distribution—is extremely slow.

So, land has been a very strategic issue, and it is still a very strategic issue.

There is currently what some have called a “grain rush”, as “wealthy, foodimporting countries and private …

The Limits Of Agrarian Reform In Brazil = 巴西土地改革的局限, Rogério Faleiros, Rogério Naques Faleiros, Neide César Vargas

South South Forum 南南論壇

Brazil is probably the only country that experienced a deep and complex process of growth and promote economic development without substantial change on the issue of land ownership. Since the Portuguese colonization, through the Land Act of 1850 and throughout the process of industrialization experienced in the twentieth century and still in progress, the land question remained almost unchanged, despite the advances resulting from the growing social and economic contradictions and the related violence observed in the field. Western Europe and countries like the United States (Homestead Act of 1862), China (the Great Leap Forward of 1959) and USSR (after …

The Impacts Of Neo-Liberal Policy On Indian Peasantry = 非洲經濟及土地政策, Arindam Banerjee

South South Forum 南南論壇

The sustainability of small-scale cultivation, which largely characterizes Indian agriculture, though not in a homogeneous or undifferentiated manner, has been one of the important casualties of the trajectory of neo-liberal policies into which the country embarked upon in the early nineties. Driven by fiscal fundamentalism, this amounted to a veritable withdrawal of the state from economic operations, more so from agriculture. A host of policies adopted like the rationalization of input subsidies, downsizing of incentive pricing, decline in public investments, shrinking public extension services and contraction of institutional credit availability in rural areas all precipitated a widespread agrarian crisis with …

Challenge Of Inclusive Growth : Global Capitalization : Institutional Cost Transferring And The Economic Of Being Poor = 包容性增長的挑戰: 全球資本化: 制度成本轉嫁與貧困經濟學, Tiejun Wen

South South Forum 南南論壇

My empirical research started with China’s experiment of rural reform during the 1980s-90s. According to the principle of experiment, only through a process of incessant falsification can we approach the truth. In the process my preliminary conclusion was the theory of institutional costs. However in later comparative studies on different countries, I found that institutional cost was not my innovation. Instead my theoretical innovation should be the discovery that the vested interest groups which appropriate the returns of an institutional transition constantly transfer the institutional costs to disadvantaged groups located at a less privileged position in the institutional structure. Therefore …

The Pension Factor: Assessing The Role Of Defined Benefit Plans In Reducing Elder Hardships, Frank Porell, Beth Almeida

Frank Porell

Traditional defined benefit (DB) pension plans have long been an important source of income for elder households seeking to maintain a middle-class standard of living after a lifetime of work. Under traditional DB plans, retirees receive a guaranteed, regular stream of income after retirement that continues until death. The monthly pension benefit is typically based on years of service to the employer, age, and salary history. Retirees also have the option to elect a joint-and-survivor benefit, to ensure that pension payments continue to a surviving spouse. DB plan participation rates among private sector American workers have sharply decreased from about …

Risk Factors For Driving Cessation Vary By Race And Ethnicity, Elizabeth Dugan, Frank Porell, Chae Man Lee

Frank Porell

Driving is related to our identity and independence as well as allowing us to get needed goods, services, and social opportunities that enrich daily life. Yet with increasing age, the risk for developing threats to medical fitness to drive increases. Driving cessation is related to a long list of negative outcomes, such as: depression, social isolation, diminished access to health care, and diminished quality of life. We investigated risks for driving cessation, paying close attention to racial differences. This study used data from the Health and Retirement Study (HRS), 1998-2008. The study included N=46, 528 older people (age 65 and …

Risk Factors For Driving Cessation Vary By Race And Ethnicity, Elizabeth Dugan, Frank Porell, Chae Man Lee

Elizabeth Dugan

Driving is related to our identity and independence as well as allowing us to get needed goods, services, and social opportunities that enrich daily life. Yet with increasing age, the risk for developing threats to medical fitness to drive increases. Driving cessation is related to a long list of negative outcomes, such as: depression, social isolation, diminished access to health care, and diminished quality of life. We investigated risks for driving cessation, paying close attention to racial differences. This study used data from the Health and Retirement Study (HRS), 1998-2008. The study included N=46, 528 older people (age 65 and …

Fun With Numbers: Disclosing Risk To Individual Investors, Christian A. Weller

Christian Weller

This paper discusses the need for better information on investment risks. The information should be relevant, concise, and accessible to individual investors. More and better information on factors that are likely to influence an investment’s performance and investors’ decisions should eventually lead to better investment decisions – more savings and higher retirement incomes. This paper presents a number of ways to disclose risk to individual investors. There are three numerical and three visual representations to risk. The discussion centers on the pros and cons of each risk representation. All risk descriptions show relevant information, are concise, and more or less …

Can Progressive Taxation Contribute To Economic Development?, Christian E. Weller, Manita Rao

Christian Weller

Financial instability has increased for many economies in the face of greater capital mobility. Eliminating capital flows, especially portfolio investment flows, may reduce volatility, but it could also result in domestic capital constraints. To overcome this dilemma, policymakers may consider alternatives, such as progressive income taxation, that could raise domestic funds. In this paper, we combine several macro economic data sources to test the link between progressive taxation and economic stability, economic growth, inequality and fiscal policy. Based on data from 1981 to 2002, we find that progressive taxation provides policymakers with the ability to conduct countercyclical fiscal policies, which …

The Interplay Between Labor And Financial Markets: What Are The Implications For Defined Contribution Accounts?, Christian E. Weller, Jeffrey B. Wenger

Christian Weller

The relationship between earnings, savings and retirement is well-known, however the linkage between labor market outcomes and financial market performance is generally unacknowledged. We examine the implications of the link between labor markets and financial markets for workers who save money in individual retirement accounts. Specifically, differences in labor market outcomes across groups may imply differences in the timing of investments, which may reduce savings over time for these groups compared to their counterparts. Using monthly data from the Current Population Survey (1979-2002) we generate hypothetical investment portfolios using stock and bond indices. We exploit differences across demographic groups in …