On the Reproducibility of Early-Stage Thermally Induced and Contact-Stir-Induced Protein Aggregation

2018 ◽  
Vol 122 (40) ◽  
pp. 9361-9372 ◽  
Author(s):  
Curtis W. Jarand ◽  
Wayne F. Reed
Keyword(s):  
Protein Aggregation ◽  
Early Stage ◽  
Thermally Induced

Structure-Based Design of Small Peptide Ligands to Inhibit Early-Stage Protein Aggregation Nucleation

2020 ◽  
Vol 60 (6) ◽  
pp. 3304-3314 ◽  
Author(s):  
Avinash Mishra ◽  
Rohit Bansal ◽  
Shravan Sreenivasan ◽  
Rozaleen Dash ◽  
Srishti Joshi ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Early Stage ◽  
Peptide Ligands ◽  
Small Peptide

Tales of the Abnormal: Nanocrystalline Grain Growth at Low Temperatures

2012 ◽  
Vol 715-716 ◽  
pp. 315-316
Author(s):  
Heiko Paul ◽  
Jules M. Dake ◽  
Carl E. Krill III
Keyword(s):  
Grain Size ◽  
Grain Growth ◽  
Early Stage ◽  
Boundary Migration ◽  
Weighted Average ◽  
Transient Stage ◽  
Thermally Induced ◽  
Size Dependent ◽  
Dependent Change ◽  
Rate Limiting

Employing x-ray diffractometry and electron microscopy, we have investigated thermally induced microstructural evolution in ball-milled nanocrystalline Fe. At low annealing temperatures, the early-stage growth of the area-weighted and volume-weighted average grain sizes deviates strongly from the parabolic behavior expected for normal grain growth. Analysis of the ratio of these two averages indicates that the width of the grain-size distribution changes with time. This result is more consistent with the occurrence of a transient stage of abnormal grain growth than with a grain-size-dependent change in the rate-limiting mechanism for grain-boundary migration.

scholarly journals Bacterial production and direct functional screening of expanded molecular libraries for discovering inhibitors of protein aggregation

2019 ◽  
Vol 5 (10) ◽  
pp. eaax5108 ◽  
Author(s):  
Dafni C. Delivoria ◽  
Sean Chia ◽  
Johnny Habchi ◽  
Michele Perni ◽  
Ilias Matis ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Early Stage ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Functional Screening ◽  
Parkinson’S Diseases ◽  
Aggregation Inhibitors ◽  
Molecular Libraries

Protein misfolding and aggregation are associated with a many human disorders, including Alzheimer’s and Parkinson’s diseases. Toward increasing the effectiveness of early-stage drug discovery for these conditions, we report a bacterial platform that enables the biosynthesis of molecular libraries with expanded diversities and their direct functional screening for discovering protein aggregation inhibitors. We illustrate this approach by performing, what is to our knowledge, the largest functional screen of small-size molecular entities described to date. We generated a combinatorial library of ~200 million drug-like, cyclic peptides and rapidly screened it for aggregation inhibitors against the amyloid-β peptide (Aβ42), linked to Alzheimer’s disease. Through this procedure, we identified more than 400 macrocyclic compounds that efficiently reduce Aβ42 aggregation and toxicity in vitro and in vivo. Finally, we applied a combination of deep sequencing and mutagenesis analyses to demonstrate how this system can rapidly determine structure-activity relationships and define consensus motifs required for bioactivity.

scholarly journals Early-Stage Temperature Gradients in Glazed Spandrels Due to Aesthetical Features to Support Design for Thermal Shock

Buildings ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 80
Author(s):  
Jacopo Montali ◽  
Luciano Laffranchini ◽  
Carlo Micono
Keyword(s):  
New York ◽  
Thermal Shock ◽  
Early Stage ◽  
Careful Analysis ◽  
Temperature Gradients ◽  
Glass Temperature ◽  
Insulation Layer ◽  
Support Design ◽  
Thermally Induced ◽  
Wide Range

Investigating thermal breakage of glass panes requires careful analysis of the environmental boundary conditions to determine the expected thermal gradient between the sunlit and shaded parts of the glass. This is particularly critical for glazed spandrels, where an opaque posterior insulation layer normally increases the system’s temperatures. The choice of the spandrel system should also be evaluated against the aesthetical impression that it conveys. The aim of this study is to understand how early design factors, such as aesthetical features like color, are driving temperature gradients in the glazed pane to design for thermal shock. Multiple finite-differences analyses in a quasi-static regime for non-ventilated, single glazed spandrels were conducted in three locations (London, New York and Mumbai). Results were then analyzed via a general linear model in SAS 9.4 and Tuckey post hoc analysis. It was shown that a low absorptance of the back insulation (e.g., light color) can lead to a wide range of possible temperature gradients depending on the glass transparency, with higher values of the thermally induced temperature gradients for more opaque glasses. Conversely, a high absorptance of the insulation layer leads to moderate values of glass temperature gradients, which are not substantially sensitive to the effect of the glass transparency.

Monitoring Early-Stage Protein Aggregation by an Aggregation-Induced Emission Fluorogen

2017 ◽  
Vol 89 (17) ◽  
pp. 9322-9329 ◽  
Author(s):  
Manjeet Kumar ◽  
Yuning Hong ◽  
David C. Thorn ◽  
Heath Ecroyd ◽  
John A. Carver
Keyword(s):  
Protein Aggregation ◽  
Early Stage ◽  
Aggregation Induced Emission

The production of hydrogen peroxide during early-stage protein aggregation: a common pathological mechanism in different neurodegenerative diseases?

2005 ◽  
Vol 33 (4) ◽  
pp. 548-550 ◽  
Author(s):  
B.J. Tabner ◽  
S. Turnbull ◽  
N.J. Fullwood ◽  
M. German ◽  
D. Allsop
Keyword(s):  
Neurodegenerative Diseases ◽  
Protein Aggregation ◽  
Early Stage ◽  
Amyloid Β ◽  
Direct Production ◽  
Esr Spin Trapping ◽  
Pathological Mechanism ◽  
Aβ Amyloid ◽  
Production Of Hydrogen ◽  
Trapping Method

By means of an ESR spin-trapping method, we have shown that Aβ (amyloid β), α-synuclein and various toxic forms of the prion protein all appear to generate H2O2in vitro. A fundamental molecular mechanism underlying the pathogenesis of cell death in several different neurodegenerative diseases could be the direct production of H2O2 during the early stages of protein aggregation.

scholarly journals α-Synuclein expression and Nrf2 deficiency cooperate to aggravate protein aggregation, neuronal death and inflammation in early-stage Parkinson's disease

2012 ◽  
Vol 21 (14) ◽  
pp. 3173-3192 ◽  
Author(s):  
Isabel Lastres-Becker ◽  
Ayse Ulusoy ◽  
Nadia G. Innamorato ◽  
Gurdal Sahin ◽  
Alberto Rábano ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Protein Aggregation ◽  
Neuronal Death ◽  
Early Stage
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