scholarly journals The Aβ40 and Aβ42 peptides self-assemble into separate homomolecular fibrils in binary mixtures but cross-react during primary nucleation

2015 ◽  
Vol 6 (7) ◽  
pp. 4215-4233 ◽  
Author(s):  
Risto Cukalevski ◽  
Xiaoting Yang ◽  
Georg Meisl ◽  
Ulrich Weininger ◽  
Katja Bernfur ◽  
...  
Keyword(s):  
Binary Mixtures ◽  
Reaction Network ◽  
Fibril Formation ◽  
Secondary Nucleation ◽  
Primary Nucleation

Reaction network starting from monomer mixtures of Aβ40 and Aβ42. Interaction at the level of primary nucleation only accelerates Aβ40 fibril formation. Separate fibrils form as secondary nucleation and elongation are highly specific.

scholarly journals The Metastability and Nucleation Thresholds of Ibuprofen in Ethanol and Water-Ethanol Mixtures

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Abdur Rashid ◽  
Edward T. White ◽  
Tony Howes ◽  
James D. Litster ◽  
Ivan Marziano
Keyword(s):  
Water Content ◽  
Propanoic Acid ◽  
Secondary Nucleation ◽  
Metastable Zone Width ◽  
Zone Width ◽  
Primary Nucleation ◽  
Metastable Zone ◽  
The Times ◽  
Induction Times ◽  
Supersaturated Solutions

To investigate the crystallization of ibuprofen [((RS)-2-(4-(2-methylpropyl) phenyl) propanoic acid)] from ethanol and water-ethanol mixtures it is necessary to know the nucleation limits of its solutions. In the absence of crystals, nucleation will seldom occur below the PNT (primary nucleation threshold). If crystals are present, nucleation will seldom occur until below the lower SNT (secondary nucleation threshold). Below the SNT, crystals will still grow with negligible nucleation. PNT and SNT values (expressed as relative supersaturationσ) have been measured at 10, 25, and 40°C for ibuprofen in ethanol and in a range of mixtures of different ethanol (E)/water (W) ratios. The induction times were determined from observing the times to nucleate for a range of different supersaturated solutions at a given temperature andE/Wratio. As expected, lowering the supersaturation leads to longer induction times. In ethanol, the SNT values are small and thus the secondary metastable zone width (MSZW) is relatively narrow with a 1 h SNT relative supersaturation typically aboutσ~ 0.05. The 1 h PNT values are much larger with values forσaround 0.3. In aqueous ethanolic mixtures at 25°C, both the PNT and SNT decrease as the water content increases.

Combination of a Single Primary Nucleation Event and Secondary Nucleation in Crystallization Processes

2011 ◽  
Vol 11 (4) ◽  
pp. 1271-1277 ◽  
Author(s):  
Somnath S. Kadam ◽  
Herman J. M. Kramer ◽  
Joop H. ter Horst
Keyword(s):  
Nucleation Event ◽  
Secondary Nucleation ◽  
Primary Nucleation

scholarly journals The Properties of α-Synuclein Secondary Nuclei are Dominated by the Solution Conditions Rather than the Seed Fibril Strain

2019 ◽  
Author(s):  
Alessia Peduzzo ◽  
Sara Linse ◽  
Alexander Buell
Keyword(s):  
Amyloid Fibrils ◽  
Lewy Bodies ◽  
The Other ◽  
Secondary Nucleation ◽  
Presynaptic Terminals ◽  
Unfolded Protein ◽  
Primary Nucleation ◽  
Other Hand ◽  
Natively Unfolded Protein ◽  
Natively Unfolded

α-synuclein (α-syn) is a natively unfolded protein predominantly localized in the presynaptic terminals of neurons. It has been shown that α-syn fibrils are the major component of abnormal neuronal aggregates known as Lewy bodies, the characteristic hallmark of Parkinson’s disease. Amyloid fibrils arise through primary nucleation from monomers, which in the case of α-syn is accelerated by suitable surfaces with an affinity for the protein, followed by the elongation of the nuclei by monomer addition. Secondary nucleation, on the other hand, corresponds to the formation of new fibrils when it is facilitated by pre-existing fibrils. While<br>α-synuclein (α-syn) is a natively unfolded protein predominantly localized in the presynaptic terminals of neurons. It has been shown that α-syn fibrils are the major component of abnormal neuronal aggregates known as Lewy bodies, the characteristic hallmark of Parkinson’s disease. Amyloid fibrils arise through primary nucleation from monomers, which in the case of α-syn is accelerated by suitable surfaces with an affinity for the protein, followed by the elongation of the nuclei by monomer addition. Secondary nucleation, on the other hand, corresponds to the formation of new fibrils when it is facilitated by pre-existing fibrils. While it is well-established that the newly added monomer in the process of fibril elongation adopts the conformation of the monomers in the seed, often called templating, it is still unclear under which conditions fibrils formed through secondary nucleation of monomers on the surface of fibrils copy the structure of the parent. Here we show by biochemical and microscopical methods that the secondary nucleation of α-syn, enabled at mildly acidic pH, leads to fibrils that structurally resemble more closely those formed de novo under the same conditions, rather than the seeds if these are formed under different solution condition. This result has important implications for the mechanistic understanding of the secondary nucleation of amyloid fibrils and its role in the propagation of aggregate pathology in protein misfolding diseases.<br>

scholarly journals Cross-talk between individual phenol-soluble modulins in Staphylococcus aureus biofilm enables rapid and efficient amyloid formation

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Masihuz Zaman ◽  
Maria Andreasen
Keyword(s):  
Staphylococcus Aureus ◽  
Self Assembly ◽  
Biofilm Formation ◽  
Opportunistic Pathogen ◽  
Amyloid Formation ◽  
Secondary Nucleation ◽  
Primary Nucleation ◽  
Functional Amyloids ◽  
High Degree

The infective ability of the opportunistic pathogen Staphylococcus aureus, recognized as the most frequent cause of biofilm-associated infections, is associated with biofilm-mediated resistance to host immune response. Phenol-soluble modulins (PSM) comprise the structural scaffold of S. aureus biofilms through self-assembly into functional amyloids, but the role of individual PSMs during biofilm formation remains poorly understood and the molecular pathways of PSM self-assembly are yet to be identified. Here we demonstrate high degree of cooperation between individual PSMs during functional amyloid formation. PSMα3 initiates the aggregation, forming unstable aggregates capable of seeding other PSMs resulting in stable amyloid structures. Using chemical kinetics we dissect the molecular mechanism of aggregation of individual PSMs showing that PSMα1, PSMα3 and PSMβ1 display secondary nucleation whereas PSMβ2 aggregates through primary nucleation and elongation. Our findings suggest that various PSMs have evolved to ensure fast and efficient biofilm formation through cooperation between individual peptides.

scholarly journals Some ice nucleation characteristics of Asian and Saharan desert dust

2006 ◽  
Vol 6 (1) ◽  
pp. 1509-1537 ◽  
Author(s):  
P. R. Field ◽  
O. Möhler ◽  
P. Connolly ◽  
M. Krämer ◽  
R. Cotton ◽  
...  
Keyword(s):  
Ice Nucleation ◽  
Cloud Chamber ◽  
Ice Crystals ◽  
Nucleation Event ◽  
Secondary Nucleation ◽  
Desert Dust ◽  
Nucleation Mode ◽  
Primary Nucleation ◽  
Condensation Mode ◽  
Deposition Mode

Abstract. The large (7 m×4 m cylinder) AIDA (Aerosol Interactions and Dynamics in the Atmosphere) cloud chamber facility at Forschungszentrum, Karlsruhe, Germany was used to test the ice nucleating ability of two desert dust samples from the Sahara and Asia. At temperatures warmer than −40°C droplets were formed before ice crystals formed, there was no deposition nucleation observed. At temperatures colder than −40°C both dust samples exhibited dual nucleation events that were observed during the same expansion experiment. The primary nucleation event occurred at ice saturation ratios of 1.1 to 1.3 and is likely to be a deposition nucleation mode. The secondary nucleation event occurred at ice saturation ratios between 1.35 and 1.5. It is unclear whether this ice nucleation event is via a further deposition mode or a condensation mode. The activated fractions of desert dust ranged from ~5–10% at −20°C to 20–40% at temperatures colder than −40°C. There was no obvious difference between the nucleation behaviour of the two dust samples.

scholarly journals Monitoramento da cristalização da lactose em soro concentrado

2017 ◽  
Vol 72 (4) ◽  
pp. 215-226
Author(s):  
Ítalo Tuler Perrone ◽  
João Pablo Fortes Pereira ◽  
Isis Rodrigues Toledo Renhe ◽  
Júlia D’Almeida Francisquini ◽  
Rodrigo Stephani ◽  
...  
Keyword(s):  
Crystal Growth ◽  
Soluble Solids ◽  
Nucleation Process ◽  
Secondary Nucleation ◽  
Primary Nucleation ◽  
Industrial Setting ◽  
Mathematical Equations ◽  
Average Size ◽  
Two Stages ◽  
Kinetics Of

The kinetics of lactose crystal growth in concentrated whey were studied in two stages. The first took place in a bench-top crystallizer and the second in an industrial crystallizer using concentrated whey obtained by vacuum evaporation, consisting of 3 treatments: crystallization by primary nucleation, by secondary nucleation with the addition of 0.05% and with the addition of 0.1% microcrystalline lactose. The average size of the crystals remained between 60.7 mm and 63.8 mm. The percentage of crystallization was greater in the secondary nucleation process than in the primary nucleation, where crystallization stabilized first. Mathematical equations which independently related crystallization times of the concentrated whey to the concentrations of soluble solids, crystallization percentage and mass of lactose in water were established, that can be used in the industrial setting to process whey. The kinetics of lactose crystal growth was not well described by models of first or second order reactions.

scholarly journals Mechanism of amyloid protein aggregation and the role of inhibitors

2019 ◽  
Vol 91 (2) ◽  
pp. 211-229 ◽  
Author(s):  
Sara Linse
Keyword(s):  
Total Concentration ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Aggregation Process ◽  
Secondary Nucleation ◽  
Toxic Species ◽  
Primary Nucleation ◽  
Effective Inhibition ◽  
Aβ Aggregation

Abstract Inhibition of amyloid β peptide (Aβ) aggregation is an important goal due to the connection of this process with Alzheimer’s disease. Traditionally, inhibitors were developed with an aim to retard the overall macroscopic aggregation. However, recent advances imply that approaches based on mechanistic insights may be more powerful. In such approaches, the microscopic steps underlying the aggregation process are identified, and it is established which of these step(s) lead to neurotoxicity. Inhibitors are then derived to specifically target steps involved in toxicity. The Aβ aggregation process is composed of at minimum three microscopic steps: primary nucleation of monomers only, secondary nucleation of monomers on fibril surface, and elongation of fibrils by monomer addition. The vast majority of toxic species are generated from the secondary nucleation process: this may be a key process to inhibit in order to limit toxicity. Inhibition of primary nucleation, which delays the emergence of toxic species without affecting their total concentration, may also be effective. Inhibition of elongation may instead increase the toxicity over time. Here we briefly review findings regarding secondary nucleation of Aβ, its dominance over primary nucleation, and attempts to derive inhibitors that specifically target secondary nucleation with an aim to limit toxicity.

scholarly journals Secondary Nucleation and the Conservation of Structural Characteristics of Amyloid Fibril Strains

2021 ◽  
Vol 8 ◽  
Author(s):  
Saeid Hadi Alijanvand ◽  
Alessia Peduzzo ◽  
Alexander K. Buell
Keyword(s):  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
Structural Characteristics ◽  
Secondary Nucleation ◽  
Primary Nucleation ◽  
Structural Preferences ◽  
Initial Seed ◽  
The Brain

Amyloid fibrils are ordered protein aggregates and a hallmark of many severe neurodegenerative diseases. Amyloid fibrils form through primary nucleation from monomeric protein, grow through monomer addition and proliferate through fragmentation or through the nucleation of new fibrils on the surface of existing fibrils (secondary nucleation). It is currently still unclear how amyloid fibrils initially form in the brain of affected individuals and how they are amplified. A given amyloid protein can sometimes form fibrils of different structure under different solution conditions in vitro, but often fibrils found in patients are highly homogeneous. These findings suggest that the processes that amplify amyloid fibrils in vivo can in some cases preserve the structural characteristics of the initial seed fibrils. It has been known for many years that fibril growth by monomer addition maintains the structure of the seed fibril, as the latter acts as a template that imposes its fold on the newly added monomer. However, for fibrils that are formed through secondary nucleation it was, until recently, not clear whether the structure of the seed fibril is preserved. Here we review the experimental evidence on this question that has emerged over the last years. The overall picture is that the fibril strain that forms through secondary nucleation is mostly defined by the solution conditions and intrinsic structural preferences, and not by the seed fibril strain.

Continuous Generation of Millimeter-Sized Glycine Crystals in Non-Seeded Millifluidic Slug Flow

Crystals ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 412 ◽  
Author(s):  
Mingyao Mou ◽  
Huayu Li ◽  
Bing-Shiou Yang ◽  
Mo Jiang
Keyword(s):  
Slug Flow ◽  
Crystallization Process ◽  
Secondary Nucleation ◽  
Flow Rates ◽  
Aspect Ratios ◽  
Cooling Crystallization ◽  
Primary Nucleation ◽  
Continuous Generation ◽  
Inner Diameter ◽  
Air Streams

Millimeter-sized α-glycine crystals were generated from continuous non-seeded cooling crystallization in slug flow. The crystallization process is composed of three steps in sequence: slug formation, crash-cooling nucleation, and growth. Stable uniform slugs of three different aspect ratios (slug length/tubing inner diameter) were formed, by adjusting the flow rates of both the solution and air streams. Besides supersaturation, the slug aspect ratio can also affect primary nucleation outcome. Stable slug flow can accommodate a relative supersaturation (C/C*) of up to 1.5 without secondary nucleation. Large glycine crystals can grow to millimeter size within 10 min, inside millimeter-sized slugs without reducing the slug quality.

A Novel Design of Heat Exchanger for Epsom Salt Cooling Crystallization

2014 ◽  
Vol 881-883 ◽  
pp. 1505-1508
Author(s):  
Ai Qun Zhang ◽  
Yan Fei Wang
Keyword(s):  
Heat Exchanger ◽  
Crystallization Process ◽  
Salt Lake ◽  
Secondary Nucleation ◽  
Primary Nucleation ◽  
Metastable Zone ◽  
Cooling Media ◽  
Novel Design ◽  
Salt Lake Brine ◽  
Epsom Salt

We introduced a design of a novel cooling heat exchanger for crystallization process of MgSO4.7H2O, and described the concepts of primary nucleation and secondary nucleation. To avoid the primary nucleation during crystallization process, the super-cooling degree limit of the salt lake brine was measured to define the supersaturation limit to MgSO4.7H2O, and the result is 1.32°C at-1°C. In this design, a primary circulation of solution is employed with a large enough flow rate to control the super-cooling degree of solution not to exceed 0.7 °C. A secondary circulation of cooling media is designed to add to this system, instead of the coldest cooling media being fed to shell directly, it is fed to the circulation pipe of the shell. It will help to prevent the supersaturation of solution exceeding the metastable zone width, thus to gurantee no primary nucleation during the Epsom salt crysatllization process.

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