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The size of amyloid seeds is known to modulate their autocatalytic amplification and cellular toxicity. However, the seed size-dependent secondary nucleation mechanism, toxicity, and disease-associated biological processes mediated by α-synuclein (α-Syn) fibrils are largely unknown. Using the cellular model and

Synucleinopathies are a class of neurodegenerative diseases, including Parkinson's disease (PD), Dementia with Lewy bodies (DLB), and Multiple System Atrophy (MSA). The common pathological hallmark of synucleinopathies is the filamentous α-synuclein (α-Syn) aggregates along with membrane components in cytoplasmic inclusions in the brain. β-Synuclein (β-Syn), an isoform of α-Syn, inhibits α-Syn aggregation and prevents its neurotoxicity, suggesting the neuroprotective nature of β-Syn. However, this notion changed with the discovery of disease-associated β-Syn mutations, V70M and P123H, in patients with DLB. It is still unclear how these missense mutations alter the structural and amyloidogenic properties of β-Syn, leading to neurodegeneration. Here, we characterized the biophysical properties and investigated the effect of mutations on β-Syn fibrillation under different conditions. V70M and P123H show high membrane binding affinity compared to wild-type β-Syn, suggesting their potential role in membrane interactions. β-Syn and its mutants do not aggregate under normal physiological conditions; however, the proteins undergo self-polymerization in a slightly acidic microenvironment and/or in the presence of an inducer, forming long unbranched amyloid fibrils similar to α-Syn. Strikingly, V70M and P123H mutants exhibit accelerated fibrillation compared to native β-Syn under these conditions. NMR study further revealed that these point mutations induce local perturbations at the site of mutation in β-Syn. Overall, our data provide insight into the biophysical properties of disease-associated β-Syn mutations and demonstrate that these mutants make the native protein more susceptible to aggregation in an altered microenvironment.

α-Synuclein (α-Syn) aggregation and amyloid formation is directly linked with Parkinson's disease pathogenesis. However, the early events involved in this process remain unclear. Here, using the in vitro reconstitution and cellular model, we show that liquid-liquid phase separation of α-Syn precedes its aggregation. In particular, in vitro generated α-Syn liquid-like droplets eventually undergo a liquid-to-solid transition and form an amyloid hydrogel that contains oligomers and fibrillar species. Factors known to aggravate α-Syn aggregation, such as low pH, phosphomimetic substitution and familial Parkinson's disease mutations, also promote α-Syn liquid-liquid phase separation and its subsequent maturation. We further demonstrate α-Syn liquid-droplet formation in cells. These cellular α-Syn droplets eventually transform into perinuclear aggresomes, the process regulated by microtubules. This work provides detailed insights into the phase-separation behaviour of natively unstructured α-Syn and its conversion to a disease-associated aggregated state, which is highly relevant in Parkinson's disease pathogenesis.

Supplier selection is the process by which firms identify, evaluate and contract with suppliers. The supplier selection process deploys a tremendous amount of a firm’s operational and financial resources and is considered as an important determinant of the success of its supply chain. In spite of being strategically important to organizations, the decision for supplier selection is often complex and unstructured. Furthermore, it is inherently a multi-criterion decision-making (MCDM) problem, which pertains to structuring and solving decision problems involving multiple criteria. The paper provides a framework to analyze and evaluate supplier selection in Indian pharmaceutical sector (IPS) using MCDM technique of fuzzy analytic hierarchy process. It intends to improve managerial decision-making in the IPS in developing a supplier selection strategy based on multi-criteria evaluation technique.

Purpose Knowledge sharing has become an integral part of organizations’ business strategies, along with aiding organizations to grow and innovate in the market, and gain competitive advantage. This paper aims to concentrate on the role of tacit knowledge sharing in fostering innovation capability of an organization. Specifically, the study considers social capital (relational, cognitive and structural) as an important precursors to tacit knowledge sharing, which in turn, influences innovation capability of an organization. The study further discusses the role that knowledge reciprocation plays in successful tacit knowledge sharing. The relation between knowledge quality and innovation capability is also discussed in the paper. Design/methodology/approach The investigation started with a review of extant literature in the field of knowledge sharing and innovation to derive a set of constructs. A set of hypotheses was developed based on the identified constructs, which was subsequently validated through a primary survey based on a structured questionnaire on a sample size of 190 respondents from the Indian industrial domain. The survey responses were subsequently analysed using the statistical technique of structural equation modeling and conclusions were drawn from the findings. Additionally, careful attention was paid in eliminating the common method bias, which is often associated with a primary survey. Findings A set of six hypotheses were derived based on the identified constructs and were subsequently validated. While validating the hypotheses, it was observed that while knowledge reciprocity, relational social capital and cognitive social capital was positive associated with tacit knowledge sharing, structural social capital did not have a significant effect on the same. Additionally, it was also observed that both tacit knowledge sharing and the quality of knowledge were positively associated with innovation capability. Practical implications The present day business marked by intense competition requires firms to be more aware of their innovative capabilities. Effective sharing of knowledge or information can be deemed as a vital component in achieving this objective. Organizations that practice and nurture innovation activities can use the findings of the current study as a part of their knowledge management strategy. In addition to using the explicit knowledge, which are structured in nature, organizations can also start using tacit knowledge to harness their innovation potential – and the findings from the current study can act as a motivational tool for them to do so. Originality/value Although there is a growing body of literature concerning the role of knowledge management in innovation, there still a dearth in discussing the role of tacit knowledge sharing in exploiting the innovation capability of an organization. The main discussion of this paper brings together a set of important constructs that exhibits the significant role that tacit knowledge sharing plays in determining the innovation capability of an organization. Furthermore, it tries to marry the concepts of social capital and tacit knowledge sharing with innovation capability, therefore adding significantly to the body of literature in knowledge management as well as innovation.

Amyloids are highly ordered nanofibrils and their tensile strength is similar to that of steel, which makes them resistant to extreme pH and temperature. Based on this rationale, we demonstrate a facile synthesis of palladium, copper, platinum, gold and silver nanocomposites using α-Synuclein (α-Syn) fibrils as a template. We showed that an α-Syn-fibril-palladium nanoparticles (α-Syn-PdNPs) composite can be used as a heterogeneous catalyst in C–H bond activation and the electrooxidation of ethanol. The study demonstrated α-Syn-PdNPs to be a superior heterogeneous catalyst for the synthesis of pharmaceutically valuable benzofuran, naphthofuran, coumarin and N-arylindole via C–H activation. Further, the electrooxidation of ethanol using α-Syn-PdNPs displayed an electrochemically active surface area of 160.6 m2 g−1, which is much higher than the previously reported values for supported Pd nanocomposites.

In the present day, business environment marked by intense competition and uncertainties, the ability of an organization and its supply chain to respond quickly to an unforeseen change in the business environment forms the key to its sustenance in the market. Since an agile supply chain comprises of a plethora of components, it is imperative that there should be a set of uncertainties associated with its functioning. The purpose of this paper is to evaluate a set of critical risks associated with the agility of an organization's supply chain. Identification and prioritization of the risks to assess their relative criticality form the backbone of the research process. This research is expected to aid the decision-makers develop robust risk management strategies as related to their organizational supply chain agility, thereby ensuring their growth and sustainability in the market.

In this paper, a cooperative transmission design for a general multi-node half-duplex wireless relay network is presented. It is assumed that the nodes operate in half-duplex mode and that channel information is available at the nodes. The proposed design involves solving a convex flow optimization problem on a graph that models the relay network. A much simpler generalized-link selection protocol based on the above design is also presented. Both the proposed flow-optimized protocol and the generalized-link selection protocol are shown to achieve the optimal diversity-multiplexing tradeoff (DMT) for the relay network. Moreover, simulation results are presented to quantify the gap between the performances of the proposed protocols and that of a max-flow-min-cut type bound, in terms of outage probability., 31 pages, 10 figures. First version submitted to Transactions on Communications, Nov. 2007. This is the revised detailed version. Further updated on Nov. 16, 2009 with minor modifications. To appear