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Herein, a facile one-pot microwave-assisted synthesis of highly water-soluble CQDs is reported and their inhibitory effect towards amyloid fibrillation process using hen egg-white lysozyme in acidic and neutral pH is explored.

Amyloidogenesis is the inherent ability of proteins to change their conformation from native state to cross β-sheet rich fibrillar structures called amyloids which result in a wide range of diseases like Parkinson's disease, Alzheimer's disease, Finnish familial amyloidosis, ATTR amyloidosis, British and Danish dementia, etc. COVID-19, on the other hand is seen to have many similarities in symptoms with other amyloidogenic diseases and the overlap of these morbidities and symptoms led to the proposition whether SARS-CoV-2 proteins are undergoing amyloidogenesis and whether it is resulting in or aggravating amyloidogenesis of any human host protein. Thus the SARS-CoV-2 proteins in infected cells, i.e., Spike (S) protein, Nucleocapsid (N) protein, and Envelope (E) protein were tested via different machinery and amyloidogenesis in them were proven. In this review, we will analyze the pathway of amyloid formation in S-protein, N-protein, E-protein along with the effect that SARS-CoV-2 is creating on various host proteins leading to the unexpected onset of many morbidities like COVID-induced Acute Respiratory Distress Syndrome (ARDS), Parkinsonism in young COVID patients, formation of fibrin microthrombi in heart, etc., and their future implications.

Due to its scale, the complexity of its products and manufacturing processes, and the capital-intensive nature of the semiconductor business, efficient product architecture design integrated with supply chain planning is critical to Intel’s success. In response to an exponential increase in complexities, Intel has used advanced analytics to develop an innovative capability that spans product architecture design through supply chain planning with the dual goals of maximizing revenue and minimizing costs. Our approach integrates the generation and optimization of product design alternatives using genetic algorithms and device physics simulation with large-scale supply chain planning using problem decomposition and mixed-integer programming. This corporate-wide capability is fast and effective, enabling analysis of many more business scenarios in much less time than previous solutions, while providing superior results, including faster response time to customers. Implementation of this capability over the majority of Intel’s product portfolio has increased annual revenue by an average of $1.9 billion and reduced annual costs by $1.5 billion, for a total benefit of $25.4 billion since 2009, while also contributing to Intel’s sustainability efforts.

This study reports the preparation of a set of hybrid materials consisting of molybdenum disulfide (MoS2) nanopatches on reduced graphene oxide (rGO) nanosheets by microwave specific heating of graphene oxide and molecular molybdenum precursors followed by thermal annealing in 3% H2 and 97% Ar. The microwave process converts graphene oxide to ordered rGO nanosheets that are sandwiched between uniform thin layers of amorphous molybdenum trisulfide (MoS3). The subsequent thermal annealing converts the intermediate layers into MoS2 nanopatches with two-dimensional layered structures whose defect density is tunable by controlling the annealing temperature at 250, 325 and 600 °C, respectively. All three MoS2/rGO samples and the MoS3/rGO intermediate after the microwave step show a high Li-ion intercalation capacity in the initial 10 cycles (over 519 mA h gMoSx−1, ∼3.1 Li+ ions per MoS2) which is attributed to the small MoS2 nanopatches in the MoS2/rGO hybrids while the effect of further S-rich defects is insignificant. In contrast, the Zn-ion storage properties strongly depend on the defects in the MoS2 nanopatches. The highly defective MoS2/rGO hybrid prepared by annealing at 250 °C shows the highest initial Zn-ion storage capacity (∼300 mA h gMoSx−1) and close to 100% coulombic efficiency, which is dominated by pseudocapacitive surface reactions at the edges or defects in the MoS2 nanopatches. The fast fading in the initial cycles can be mitigated by applying higher charge/discharge currents or extended cycles. This study validates that defect engineering is critical for improving Zn-ion storage.

Realist evaluation (RE) is a theory-driven evaluation approach inspired by scientific realism. It has become increasingly popular in the field of global health where it is often applied in low- and middle-income countries. This makes it timely to discuss RE's relationship to the emerging decolonisation of global health movement. In this short perspective, we argue that the principles and practices that underpin RE have great potential to contribute to the decolonisation endeavour. Both the focus on the inclusion of local stakeholders and the openness to the rival theories these stakeholders bring to the fore, are promising. However, in practice, we see that a lack of acknowledgement of power imbalances and different ontologies and an overreliance on Western-based theories thwart this potential. We therefore suggest that realist evaluations performed by external researchers, especially in the field of global health, should actively engage with issues of (power) inequities. This is not only the just thing to do, but will also contribute to a better understanding of the intervention and may facilitate the emancipation of the disenfranchised. One way of doing this is through the adoption of participatory (action) research methods, currently underused in realist evaluations. We finally give a short example of an evaluation that combines emancipatory and participatory practice development with a realist approach. The Afya-Tek project in Tanzania has an innovative bottom-up approach throughout the full evaluation cycle and shows the possible strength of the proposed combination to create better interventions, more empowered stakeholders, and more illuminating programme theories.

Alzheimer’s Disease is a neurodegenerative disease for which no cure is available at present. The presence of amyloid plaques in the extracellular space of neural cells is the key feature of this fatal disease. Amyloid-Beta (Aβ) is a 40-42 amino acid peptide and the main component of amyloid plaques. This peptide is produced by the proteolysis of Amyloid Precursor Protein by presenilin. Deposition of 42 residual Aβ peptides forms fibrils structure, leading to disruption of neuron synaptic transmission, inducing neural cell toxicity, ultimately leading to neuron death. To modulate the amyloidosis of Aβ peptides, various novel peptides have been investigated via molecular docking and molecular dynamic simulation studies. The sequence-based peptides were designed and investigated for their interaction with Aβ42 monomer and fibril using the molecular docking method, and their influence on the structural stability of target proteins was studied using molecular simulations. According to the docking results, amongst all the synthetic peptides, the peptide YRIGY (P6) has the highest binding affinity with Aβ42 fibril, and the peptide DKAPFF (P12) shows better binding with Aβ42 monomer. Moreover, simulation results also suggest that the higher the binding affinity, the better the inhibitory action. From these findings, it is suggested that both the peptides can modulate the amyloidogenesis, but peptide (P6) has better potential for the disaggregation of the fibrils, whereas peptide P12 stabilizes the native structure of the Aβ42 monomer more effectively and hence can serve as a potential amyloid inhibitor. Thus, these peptides can be explored as therapeutic agents against Alzheimer’s Disease.

The successful synthesis of multi-component molecular solids such as cocrystals typically requires a large number of experiments before a new solid form of the target compound emerges with improved bulk properties. In order to focus and guide cocrystal synthesis we evaluated three different protocols (individually and combined) for predicting whether a cocrystal would form dur-ing attempted cocrystallizations between six active pharmaceutical ingredients and 42 potential coformers of the general interest. A blend of different methods gave the best results and a combination of protocols based on molecular complementarity (MC) and hydrogen-bond propensity (HBP), correctly predicted the outcome of 81% of experiments, whereas a combination of MC, and a protocol based on hydrogen-bond energies (HBE) delivered an overall success rate of 77% (including true positives and true negatives). The ease with which these methods can be implemented prior to large-scale experimental cocrystal screening, means that the choice of potential coformers may be narrowed effectively and the experimental search can be substantially optimized.

An automated application, CoForm, was used for predicting the outcomes of attempted co-crystallizations between two active pharmaceutical ingredients, loratadine and desloratadine, and 41 potential co-formers from the general interest (OGI) list. The predictive abilities of the app were compared to structure-informatics tools based on hydrogen-bond propensity (HBP) and molecular complementarity (MC). The results indicate that CoForm delivered a success rate of 78% for both loratadine and desloratadine compared to 76% and 54%, respectively (HBP), and 39% and 22%, respectively (MC).

All proteins have the inherent ability to undergo transformation from their native structure to a β sheet rich fibrillar structure, called amyloid when subjected to specific conditions. Proteins with a high propensity to form amyloid fibrils have been implicated in a variety of disorders like Alzheimer's disease, Parkinson's disease, Type II diabetes, Amyotrophic Lateral Sclerosis (ALS) and prion diseases. Among the various critical factors that modulate the process of amyloid formation, disulfide bonds have been identified as one of the key determinants of amyloid propensity in proteins. Studies have shown that intra-molecular disulfide bonds impart stability to the native structure of a protein and decrease the tendency for amyloid aggregation, whereas intermolecular disulfide bonds aid in the process of aggregation. In this review, we will analyze the varying effects of both intra as well as inter-molecular disulfide bonds on the amyloid aggregation propensities of a few proteins associated with amyloid disorders.

Proteins, under certain circumstances such as defective quality control mechanism, mutations and altered environmental conditions, undergo misfolding and assemble into highly ordered beta-sheet structured fibrillar aggregates called amyloid fibrils. Formation of amyloid is seen in most of the protein linked degenerative diseases like Alzheimer's disease, Parkinson's disease, Huntington's disease, Type II diabetes mellitus and many more. Amyloid fibril forms via intermediate state(s), and is known to follow a nucleated condensation polymerization mechanism. Though extensive research is being carried out towards finding a therapeutic solution to the amyloidosis, an effective treatment to these diseases still remains elusive and also the mechanism of amyloidogenesis largely remains unclear. In recent times, carbon quantum dots (CQDs) are gaining the attention of researchers due to their semi-conductive nature, excellent physio-chemical properties, high surface to volume ratio, optical properties and mainly bio-compatibility. In the current study, we have synthesized CQDs from commonly available kitchen spice mix and explored their role in amyloidogenesis using hen egg white lysozyme (HEWL) as a model protein. The results clearly demonstrate the amyloid inhibitory as well as disaggregation potential of CQD by forming a stable complex with HEWL and thereby increasing the energy barrier for the aggregation process.

Two different structure-informatics based methods and one approach based on hydrogen-bond interaction energies were evaluated for their abilities to predict the experimental outcomes of attempted co-crystallisations between two known drug molecules, Nevirapine and Diclofenac, and a series of potential co-formers. The hydrogen-bond propensity (HBP) tool gave the correct result in 26 out of 30 cases, whereas a hydrogen-bond coordination (HBC) method predicted the correct outcome in 22 out of 30 cases. Finally, calculated hydrogen-bond energies (HBE) using a simple electrostatic model, gave the correct result in 23 out of 30 experiments. In those cases, where the crystal structure of a co-crystal of either Nevirapine or Diclofenac was known, we also examined how well the three methods predicted which primary hydrogen-bond interactions were present in the crystal structure. HBP correctly predicted 6 out of 6 cases, HBC could not predict any of the synthon formations correctly, and HBE successfully predicted 1 out of 6 cases.

Amyloids are highly ordered beta sheet rich stable protein aggregates, which have been found to play a significant role in the onset of several degenerative diseases such as Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, Type II diabetes mellitus and so on. Aggregation of proteins leading to amyloid fibril formation via intermediate(s), is thought to be a nucleated condensation polymerization process associated with many pathological conditions. There has been extensive research to identify inhibitors of these disease oriented aggregation processes. In recent times, quantum dots, with their unique physico-chemical properties have grabbed the attention of scientific community due to its applications in medical sciences. Quantum dots are nano-particles usually made of semiconductor materials which emit fluorescence upon radiation. The wavelength of fluorescence emission varies with changes in size of quantum dots. Several studies have reported significant inhibitory effects of these quantum dots towards amyloidogenesis, thereby presenting themselves as promising candidates against amyloidosis. Further, studies have also revealed amyloid detection capacity of quantum dots with sensitivity and specificity better than conventional probes. In the current review, we will discuss the various effects of quantum dots on protein aggregation pathways, their mechanism of actions and their potentials as effective therapeutics against amyloidosis.

Co-crystallizations can be utilized for generating new solid forms of a target substance in order to alter or enhance some specific bulk physical property. Generally, selection of the co-former (the necessary partner for the target molecule) is based on existing structural information about molecular recognition events involving complementary functional groups, and extensive experimental screening methods. In this study, we utilize structure-informatics in an attempt to predict if two different molecules will form a co-crystal or not. Our study is based on hydrogen-bond propensity (HBP), and the key premise of our approach rests on whether target–co-former interactions are more likely to take place than either target–target or co-former–co-former hydrogen bonds. We examined six different target molecules in combination with 25 possible co-formers each and used the HBP protocol for predicting if a co-crystal would form or not. The predictions were then compared with results from an experimental co-crystal screen of the 150 different combinations. The correct outcome was successfully predicted 92–95% of the time which shows that for this series of small molecules, HBP is a very reliable indicator for determining if a co-crystal will form between a target molecule and a particular co-former.

Amyloid fibrils are highly stable protein fibrillar aggregates believed to be involved in various neurodegenerative diseases, which include Alzheimer’s disease, Parkinson’s disease, and prion diseases. Inhibiting the aggregation process is a potential strategy to prevent diseases caused by amyloid formation. In this regard, nanoparticles have emerged as promising candidates owing to their unique physical/chemical properties of small size, large surface area, biocompatibility, biodegradability, non-toxicity, and ease of functionalization. Human Serum Albumin (HSA) is a soluble multidomain monomeric protein that interacts with various ligands and hormones, aiding in their transport, distribution, metabolism in the circulatory system, and also plays a vital role in extracellular fluid volume stabilization. Under certain in vitro conditions, HSA has been reported to undergo conformational changes leading to fibril formation and hence acts as a suitable model for studying amyloidogenesis. In this review, we have explored the effects of various nanoparticles on HSA aggregation and their mechanism of action. The study will throw light on the mechanistic details of nanoparticle-mediated amyloid modulation, which will help in the development of effective therapeutics against amyloidosis.

Misfolded and natively disordered globular proteins tend to aggregate together in an interwoven fashion to form fibrous, proteinaceous deposits referred to as amyloid fibrils. Formation and deposition of such insoluble fibrils are the characteristic features of a broad group of diseases, known as amyloidosis. Some of these proteins are known to cause several degenerative disorders in humans, such as Amyloid-Beta (Aβ) in Alzheimer's disease (AD), human Islet Amyloid Polypeptide (hIAPP, amylin) in type 2 diabetes, α-synuclein (α-syn) in Parkinson's disease (PD) and so on. The fact that these proteins do not share any significant sequence or structural homology in their native states make therapy quite challenging. However, it is observed that aggregation-prone proteins and peptides tend to adopt a similar type of secondary structure during the formation of fibrils. Rationally designed peptides can be a potent inhibitor that has been shown to disrupt the fibril structure by binding specifically to the amyloidogenic region(s) within a protein. The following review will analyze the inhibitory potency of both sequence-based and structure-based small peptides that have been shown to inhibit amyloidogenesis of proteins such as Aβ, human amylin, and α-synuclein.

In this work, the core carbon nanoparticles (BM CNs) and polyethylene glycol 400 (PEG400)-capped BM CNs were synthesised from Butea monosperma flower extract via the facile direct heating method. They were investigated for their intriguing properties and in vitro antioxidation activity in comparison with Carica papaya seed (CPS) extract via DPPH assay. The CNs were characterised by DLS, XRD, HR-TEM, TGA, FT-IR, UV–vis spectral analysis and quantum yield measurement. The PEGylated CNs demonstrated decent quantum yield, favourable size, and turbostratic carbon phase apart from better stability and dispersion nature as compared to the uncapped entity. The mildly stable uncapped sample with zeta potential −17.9 mV featured its extensively aggregated form, unlike the capped sample with −23.0 mV zeta potential, which sheds light on its enhanced stability by PEG400. Antiradical capacities of the CNs in comparison with CPS extract demonstrated the PEG400-bound nanomaterial of its superior antiradical activity against the other two controls. This study provides an insight into the novel polymer-CNs’ potent antioxidant property which can be further explored for its incorporation in targeted drug delivery and other biomedical applications.

A high entropy alloy containing ZrNbAlTiV in equiatomic ratio was produced by suction casting technique. Cross-sectional microstructure showed equiaxed morphology at the peripheral and dendrite morphology at the center region of the sample. Electron microscopic analysis revealed that the single phase and the dendrite phase have ordered bcc structure and the inter-dendrite phase has hexagonal structure. Compositions of the single phase and dendrites were same as that of the alloy composition, whereas, edges of dendrite and inter-dendrite regions show preferential partitioning of Nb and Zr respectively. These results have been rationalized in terms of cooling rates and interactions among elements.

Fluctuation conductivity has been studied in the past and viewed as a precursor to the incipience of superconductivity in various low-dimensional superconductors. Bulk metallic glasses (BMG) could be a new genre of materials for studying fluctuation superconductivity in bulk materials, as a recent finding shows that many of them have medium range order (MRO) correlated with a fractal network. MRO being very much smaller than the superconducting coherence length, makes superconductivity in this material very much susceptible to fluctuations. Here, we show the signature of excess conductivity, a hallmark of fluctuation conductivity, just above the superconducting transition of Zr52Ti6Al10Cu18Ni14 metallic glass. The fluctuation superconductivity is correlated with the MRO structure (established using the latest fluctuation electron microscopy technique) and a reduced dimension identified to the fractal dimension.

It was otherwise an unremarkable November bus ride from Antwerp to Montreux; cold, but in the rather warm company of early career researchers who were to soon become the first cohort of Emerging Voices for Global Health (EV4GH; http://www.ev4gh.net). On that ride, 52 early career health system researchers from 30 countries began a journey. Little did they know it would continue for over a decade, gathering in its wake, 208 more early career researchers from 60 countries, overwhelmingly from the global south. The EV4GH programme has come a long way, from the first meeting at the 2010 annual colloquium of Institute of Tropical Medicine, Antwerp, Belgium, and the subsequent road trip from Antwerp to the first Global Symposium on Health Systems Research at Montreux, Switzerland. EV4GH began as a leadership and capacity-building programme incubated within the Institute of Tropical Medicine, Antwerp (ITM-A) by a team led by Professor Wim Van Damme. With an explicit commitment to switching the poles (between the global north to the global south), the team at ITM-A sought to design a unique programme to provide early career researchers with communication skills to critically examine global health agendas and events, and more importantly to not become passive consumers of evidence in global health events (such as the one that was, at the time, coming up in Montreux). This was a disruptive idea. Early career researchers typically enter global events in awe of the authoritative and prominent names featured in keynotes and panels. Indeed, the first EV4GH programme began by acknowledging the elderly white male high-income country dominance of the global health agenda. The programme wanted to do something about it, beginning at that first symposium in Montreux. This year, 2020, marks the 10th year of this programme and offers an opportunity to look back and look within. …

We propose Nb-1Zr-0.1C alloy as an alternate candidate for SCRF cavity application. The material having a good combination of mechanical properties like strength, ease of deformability, ability to withstand adverse conditions like radiation exposure and higher first penetration field HP than niobium metal makes it another candidate material for superconducting cavity application.

Many degenerative disorder such as Parkinsons, Alzheimers, Huntingtons disease, etc are caused due to the deposition of amyloid fibrils, formed due to the ordered aggregation of misfolded/unfolded proteins. Misfolded or unfolded proteins aggregate mostly through hydrophobic interactions which are unexposed in native state, but become exposed upon unfolding. To counteract amyloid related diseases, inhibition of the protein self assembly into fibril is a potential therapeutic strategy. The study aims at investigating the effect of selected compounds, namely trehalose and magnesium chloride hexahydrate towards inhibition and disaggregation of amyloid fibrils using Hen Egg White Lysozyme as a model. We further attempted to understand the mechanism of action with the help of various biophysical, microscopic as well as computational studies. A common mechanism of action was identified where the selected compounds exert their anti-amyloidogenic effects by altering HEWL conformations characterized by reduction in the beta sheet content and decrease in exposed hydrophobic surfaces. The altered conformation seems to have lesser amyloidogenic propensity leading to inhibition as well as disaggregation of amyloids.

Potentials of intermetallics for high temperatures were realized in the early 1900s. But initial attempts from time to time failed due to inadequate ductility as well as poor high-temperature creep strength exhibited by the intermetallic phases. From these early attempts three main ideas germinated. First, addition of ternary elements can improve properties of intermetallic phases dramatically. Second, introduction of new phases not only can change properties but also allow tailoring of the microstructure according to the demand of the application requirements. Third, combining brittle phase along with a ductile matrix it is possible to develop a composite material that encompasses the inherent limitations of the intermetallic phases. Based on these points, a new series of alloys and phases were developed. These recent developments and innovations are summarized in this chapter. The first part of the chapter is devoted to various intermetallic phases, which are under active consideration, and the second part of the chapter is focused on the development of refractory metal-based alloy and high-entropy alloy systems.

Modulation of gamma-secretase cleavage of Amyloid Precursor Protein (APP) to control the level of Amyloidbeta (A-beta) peptide is one of the strategies to develop therapy for Alzheimer’s disease. Presenilin is a subunit and the catalytic core of gamma-secretase. It has Asp 257 and Asp 385 residues, which are essential for catalytic activity and thus serve as the region of interest for screening of potential gamma-secretase inhibitors. In the present study, in silico screening of drug molecules has been performed in an attempt to identify effective inhibitors of presenilin. Ligand-based pharmacophore models generated with reported inhibitor molecules have been used as query for screening from DrugBank database. Inhibitory activity (IC 50 ) of the screening hits is predicted using a QSAR model developed. The selected molecules have been subjected to docking study against Presenilin1 C-terminal fragment that houses Asp 385 in place of presenilin, as its structure is unavailable. Finally, 46 potential inhibitor molecules were selected based on scores of scoring function and interaction with Asp 385. The selected compounds have spatial arrangement of features essential for binding to presenilin, desired inhibitory activity against processing of APP to A-beta by gamma-secretase and selective interaction with specific amino acids in ligand-protein docked complexes.

The transformation of polypeptide chains from their globular native structure to fibrillar aggregates has been a matter of great concern because of the involvement of these aggregates in the onset of several degenerative diseases. These aggregates exhibit highly ordered cross β sheet structures and are known as ‘amyloids’. Formation of amyloids in the body is associated with cytotoxicity due to direct interaction of the aggregated species with the cell membrane leading to cellular permeability or due to loss of functionality of the proteins involved in the amyloid formation. The preference of polypeptide chains to remain in their native conformation or to aggregate into amyloids is guided by several factors such as its conformation at specific condition, concentration, physicochemical properties of the amino acid sequence and so on. In the current review, we have reviewed the different factors that guide the transition of proteins from their natively folded state to the amyloidogenic state. Understanding the critical determinants of amyloidogenesis is vital towards deciphering the molecular mechanism of amyloidogenesis and for the development of effective therapeutics against amyloidosis. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.

Amyloid plaque is associated with several neuronal and non-neuronal degenerative diseases. More than twenty human proteins can fold abnormally to form pathological deposits like amyloid plaque. Strategies for treating such diseases include therapies designed to decrease protein plaque formation or its complete clearance, but monitoring/clinical trials of these treatments are limited by the lack of effective methods to monitor amyloid deposits in the organs/tissues of living patients. The current study shows binding and staining ability of quinacrine to protein amyloid deposits, using Hen Egg White Lysozyme (HEWL) as model system and characterization of its binding interaction with HEWL, employing several biophysical techniques. Since quinacrine can pass the blood brain barrier, the current report suggests potential application of quinacrine for antemortem diagnostic of amyloid.

Background Deposition of protein fibrillar aggregates called amyloids in the tissue, is the principal cause of several degenerative diseases. Here, we have shown the disaggregation potential of rottlerin towards hen egg white lysozyme (HEWL) fibrils formed under alkaline conditions (pH-12.2). Methods Several biophysical methods like Atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR) and fluorescence emission spectra were used for the study. Results and conclusion Rottlerin exhibited instantaneous disaggregation effect on HEWL fibrils as monitored by Thioflavin T assay, anisotropy study and AFM imaging. Further we have monitored the conformational changes induced by rottlerin on the fibril in terms of surface hydrophobicity and secondary structure through 8-anilino-1-naphthalene sulfonic acid (ANS) fluorescence and FTIR study respectively. We have also attempted to elucidate the type of interaction between HEWL and rottlerin at pH-12.2 employing techniques like quenching study and FTIR. General significance Rottlerin seems to have potential application as anti-amyloid compound.

Fibrillar protein aggregates called amyloids are the hallmark of several degenerative diseases. Identification of common drugs which are capable of blocking or inhibiting protein aggregation may be considered as one of the therapeutic approaches directed against amyloid diseases. The present study describes the effect of a few small molecule compounds like clotrimazole, sulconazole and rottlerin towards amyloidogenesis of two model proteins unrelated in terms of structure and sequence such as hen egg white lysozyme and cytochrome c to test promiscuity of amyloid inhibition. Amyloid progression was monitored through Thioflavin T assay and atomic force microscope imaging. Also, the thermodynamic basis of inhibition of fibrillogenesis was analyzed through equilibrium unfolding and unfolding kinetic studies of the proteins in presence of the compounds. Structural alterations in the aggregation-prone intermediate state conformation of the protein in presence of the compounds were monitored through 1-anilino-8-naphthalene sulfonate (ANS) binding studies. Our findings shed some light on the key interactions that guide the path towards protein aggregation and the probable structural and thermodynamic mechanism of inhibition which may provide useful guidelines in development of therapeutics against amyloid diseases.

Protein amyloids are characterized by aggregates that usually consist of fibres containing misfolded proteins and having a cross β-sheet conformation. These aggregates can eventually lead to several degenerative diseases like Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Huntington’s disease and Parkinson’s disease. The present study describes the effect of chemically synthesized polyvinylpyrrolidone (PVP)-conjugated gold nanoparticles (PVP-AuNps) on hen egg white lysozyme (HEWL) amyloids. The synthesized nanoparticles have been characterized using various biophysical techniques like Ultraviolet-Visible (UV-Vis) Spectroscopy, Transmission electron microscopy (TEM), X-ray diffraction (XRD) analysis, dynamic light scattering (DLS), zeta-potential measurement and Fourier transform infrared spectroscopy (FTIR). The aggregation studies showed that PVP acts as a partial inhibitor of HEWL amyloidogenesis. However, when conjugated to gold nanoparticle surface, it leads to complete inhibition of amyloid formation. Apart from inhibition, PVP-conjugated gold nanoparticles also exhibited a significant disaggregation effect on mature amyloids and hence can be exploited as an effective therapeutic agent against hereditary systemic amyloidosis.

Vitamin C (L-ascorbate) is a good antioxidant. Because of its water soluble nature it can work both inside and outside the cells to combat free radical damage. It has several applications starting from application in cancer therapeutics to treatment of common cold. Human, primates and guinea pigs can not synthesize this nutrient and must have to take this nutrient with diet. The current review brings together information available about the applications of Vitamin C with emphasis on antioxidant property and application in cancer therapy. The contradicting reports about application of Vitamin C in cancer therapy are also discussed.

Tissue deposition of fibrillar protein aggregates called amyloid is the root cause of several degenerative diseases. Thus identification of compounds which can prevent or reduce protein aggregation can serve as a potential therapeutic target. In the present study we have shown inhibitory effect of sodium tetrathionate toward Hen egg white lysozyme (HEWL) amyloidogenesis at pH 2.0. Our study reveals that without sulfonation, sodium tetrathionate prevents amyloid fibril progression. Moreover, it shows that formation of disulfide bonds rather than exposure of hydrophobic surface in protein plays a critical role in initiating fibrillation process. Inhibitory effect of reducing agent β-mercaptoethanol toward fibrillation process also confirms the involvement of disulfide bond in initiating HEWL amyloidogenesis. These results provide important information toward understanding key interactions that guide amyloidogenesis, which may facilitate development of potential therapeutics.

We identified a molten globule-like intermediate of 2,5-diketo-d-gluconate reductase A (DKGR) at pH 2.5, which has a prominent β-sheet structure. The molten globule state of the protein shows amyloidogenic property >50 μm protein concentration. Interestingly, a 1:1 molar ratio of curcumin prevents amyloid formation as shown by the Thioflavin-T assay and atomic force microscopy. To the best of our knowledge, this is the first report on amyloid formation by an (α/β)8-barrel protein. The results presented here indicate that the molten globule state has an important role in amyloid formation and potential application of curcumin in protein biotechnology as well as therapeutics against amyloid diseases.

Trypanothione reductase is an important target enzyme for structure-based drug design against Leishmania. We used homology modeling to construct a three-dimensional structure of the trypanothione reductase (TR) of Leishmania infantum. The structure shows acceptable Ramachandran statistics and a remarkably different active site from glutathione reductase(GR). Thus, a specific inhibitor against TR can be designed without interfering with host (human) GR activity.

The current article describes the biophysical characterization and folding studies of fibroblast growth factor homologous factor-1b (FHF-1b) in comparison with acidic fibroblast growth factor (FGF-1). Our data indicates that FHF-1 is significantly more stable than FGF-1. The folding mechanism of these two proteins seems to be different although they share high degree of sequence and structural similarity. FHF-1 unfolds through stable intermediate state while unfolding of FGF-1 is two-state. Interestingly, low concentration of sodium dodecyl sulfate (SDS) drives the folding pathway of FHF-1b to two-state.