Corrigendum to “Elucidating the weak protein-protein interaction mechanisms behind the liquid-liquid phase separation of a mAb solution by different types of additives” [Eur. J. Pharm. Biopharm. 120 (2017) 1–8]

2018 ◽  
Vol 125 ◽  
pp. 182
Author(s):  
Guoliang Wu ◽  
Shujing Wang ◽  
Zhou Tian ◽  
Ning Zhang ◽  
Han Sheng ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Protein Interaction ◽  
Liquid Phase Separation ◽  
Interaction Mechanisms ◽  
Protein Protein Interaction ◽  
Different Types ◽  
Liquid Liquid Phase Separation

scholarly journals Liquid-liquid phase separation in secondary organic aerosol particles produced from α-pinene ozonolysis and α-pinene photo-oxidation with/without ammonia

2019 ◽  
Author(s):  
Suhan Ham ◽  
Zaeem Bin Babar ◽  
Jaebong Lee ◽  
Hojin Lim ◽  
Mijung Song
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Secondary Organic Aerosol ◽  
Cloud Condensation Nuclei ◽  
Aerosol Particles ◽  
Organic Aerosol ◽  
Liquid Phase Separation ◽  
Photo Oxidation ◽  
Different Types ◽  
Liquid Liquid Phase Separation

Abstract. Recently, liquid–liquid phase separation (LLPS) of secondary organic aerosol (SOA) particles free of inorganic salts has been intensively studied because of their importance on cloud condensation nuclei (CCN) properties. Herein, we investigated LLPS in four different types of SOA particles generated from α-pinene ozonolysis and α-pinene photo-oxidation in the absence and presence of NH3. LLPS was observed in SOA particles produced from α-pinene ozonolysis at ~ 95.8 % relative humidity (RH) and α-pinene ozonolysis with NH3 at ~ 95.4 % RH. However, LLPS was not observed in SOA particles produced from α-pinene photo-oxidation and α-pinene photo-oxidation with NH3. With datasets of average oxygen to carbon elemental ratio (O : C) for different types of SOA particles of this study and previous studies, LLPS occurred when the O : C ratio was less than ~ 0.44 and LLPS did not occur when the O : C ratio was greater than ~ 0.40. When LLPS was observed, the two liquid phases were present up to ~ 100 % RH. This result can help to predict more accurate results of CCN properties of organic aerosol particles.

scholarly journals Sequence determinants for the aggregation and cytotoxicity of proteins within condensates generated by liquid-liquid phase separation

2020 ◽  
Author(s):  
Michele Vendruscolo ◽  
Monika Fuxreiter
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Human Disease ◽  
Liquid Droplet ◽  
Liquid Phase Separation ◽  
Functional Protein ◽  
Mechanisms Of Toxicity ◽  
Different Types ◽  
Lateral Sclerosis ◽  
Liquid Liquid Phase Separation

AbstractThe transition between the native and amyloid states of proteins can proceed via a deposition pathway through oligomeric intermediates or via a condensation pathway through liquid droplet intermediates generated through liquid-liquid phase separation. The maturation of these droplet intermediates into ordered assemblies has been associated with human disease, including in particular amyotrophic lateral sclerosis (ALS), although the mechanisms of toxicity have not been yet clarified. Here we investigate the processes by which ALS-related mutations give rise to cytotoxicity along the condensation pathway. Based on the sequence-determinants of the different types of interactions stabilising the droplet and amyloid states, we accurately predict the levels of toxicity of about 50,000 deep mutagenesis variants of TDP-43 prion-like domain. We find that condensation is not typically initiated by structural ordering, but rather through non-specific interactions, and that the cytotoxicity of ALS-related TDP-43 mutations stems from promiscuous interactions within the droplet intermediates, rather than from the mature aggregates. These results provide insights into the mechanisms by which condensates convert into amyloids and their links with human disease.SignificanceProtein liquid-liquid phase separation underlies the formation of functional protein condensates, which upon dysregulation can mature into cytotoxic amyloid-containing aggregates. The sequence-based principles governing this pathway, and the mechanisms giving rise to cytotoxicity, however, are still not known in detail. Here, based on the different amino acid codes leading to the droplet and amyloid states, we show how one can predict the toxicity of the intermediate states along the condensation pathway. Our results highlight that this toxicity originates from the interaction promiscuity of amyloid-containing intermediates, in particular those with ALS-related mutations, rather than from the mature amyloid state. These results contribute to our understanding of the mechanisms through which TDP-43 mutations are linked to ALS.

scholarly journals Liquid–liquid phase separation in secondary organic aerosol particles produced from <i>α</i>-pinene ozonolysis and <i>α</i>-pinene photooxidation with/without ammonia

2019 ◽  
Vol 19 (14) ◽  
pp. 9321-9331 ◽  
Author(s):  
Suhan Ham ◽  
Zaeem Bin Babar ◽  
Jae Bong Lee ◽  
Ho-Jin Lim ◽  
Mijung Song
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Secondary Organic Aerosol ◽  
Cloud Condensation Nuclei ◽  
Aerosol Particles ◽  
Organic Aerosol ◽  
Liquid Phase Separation ◽  
Liquid Phases ◽  
Different Types ◽  
Liquid Liquid Phase Separation

Abstract. Recently, liquid–liquid phase separation (LLPS) of secondary organic aerosol (SOA) particles free of inorganic salts has been intensively studied due to the importance of cloud condensation nuclei (CCN) properties. In this study, we investigated LLPS in four different types of SOA particles generated from α-pinene ozonolysis and α-pinene photooxidation in the absence and presence of ammonia (NH3). LLPS was observed in SOA particles produced from α-pinene ozonolysis at ∼95.8 % relative humidity (RH) and α-pinene ozonolysis with NH3 at ∼95.4 % RH. However, LLPS was not observed in SOA particles produced from α-pinene photooxidation and α-pinene photooxidation with NH3. Based on datasets of the average oxygen to carbon elemental ratio (O:C) for different types of SOA particles from this study and from previous studies, there appears to be a relationship between the occurrence of LLPS and the O:C of the SOA particles. When LLPS was observed, the two liquid phases were present up to ∼100 % RH. This result can help more accurately predict the CCN properties of organic aerosol particles.

scholarly journals Liquid-Liquid Phase Separation of Tau Driven by Hydrophobic Interaction Facilitates Fibrillization of Tau

2021 ◽  
Vol 433 (2) ◽  
pp. 166731
Author(s):  
Yanxian Lin ◽  
Yann Fichou ◽  
Andrew P. Longhini ◽  
Luana C. Llanes ◽  
Pengyi Yin ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Hydrophobic Interaction ◽  
Liquid Phase Separation ◽  
Liquid Liquid Phase Separation

scholarly journals Amyloid Aggregation under the Lens of Liquid–Liquid Phase Separation

2020 ◽  
pp. 368-378
Author(s):  
Yanting Xing ◽  
Aparna Nandakumar ◽  
Aleksandr Kakinen ◽  
Yunxiang Sun ◽  
Thomas P. Davis ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Liquid Phase Separation ◽  
Amyloid Aggregation ◽  
Liquid Liquid Phase Separation

scholarly journals Observation of liquid-liquid phase separation of ataxin-3 and quantitative evaluation of its concentration in a single droplet using Raman microscopy

2021 ◽  
Author(s):  
Kazuki Murakami ◽  
Shinji Kajimoto ◽  
Daiki Shibata ◽  
Kunisato Kuroi ◽  
Fumihiko Fujii ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Neurodegenerative Diseases ◽  
Protein Aggregation ◽  
Quantitative Evaluation ◽  
Raman Microscopy ◽  
Liquid Phase Separation ◽  
Biological Processes ◽  
Single Droplet ◽  
Liquid Liquid Phase Separation

Liquid–liquid phase separation (LLPS) plays an important role in a variety of biological processes and is also associated with protein aggregation in neurodegenerative diseases. Quantification of LLPS is necessary to...

scholarly journals Targeting NSD2-mediated SRC-3 liquid–liquid phase separation sensitizes bortezomib treatment in multiple myeloma

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Liu ◽  
Ying Xie ◽  
Jing Guo ◽  
Xin Li ◽  
Jingjing Wang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Drug Resistance ◽  
Phase Separation ◽  
Liquid Phase ◽  
Liquid Phase Separation ◽  
Acquired Drug Resistance ◽  
Bortezomib Treatment ◽  
Liquid Liquid Phase Separation

AbstractDevelopment of chemoresistance is the main reason for failure of clinical management of multiple myeloma (MM), but the genetic and epigenetic aberrations that interact to confer such chemoresistance remains unknown. In the present study, we find that high steroid receptor coactivator-3 (SRC-3) expression is correlated with relapse/refractory and poor outcomes in MM patients treated with bortezomib (BTZ)-based regimens. Furthermore, in immortalized cell lines, high SRC-3 enhances resistance to proteasome inhibitor (PI)-induced apoptosis. Overexpressed histone methyltransferase NSD2 in patients bearing a t(4;14) translocation or in BTZ-resistant MM cells coordinates elevated SRC-3 by enhancing its liquid–liquid phase separation to supranormally modify histone H3 lysine 36 dimethylation (H3K36me2) modifications on promoters of anti-apoptotic genes. Targeting SRC-3 or interference of its interactions with NSD2 using a newly developed inhibitor, SI-2, sensitizes BTZ treatment and overcomes drug resistance both in vitro and in vivo. Taken together, our findings elucidate a previously unrecognized orchestration of SRC-3 and NSD2 in acquired drug resistance of MM and suggest that SI-2 may be efficacious for overcoming drug resistance in MM patients.

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