scholarly journals Controlling Amphiphilic Polymer Folding Beyond the Primary Structure with Protein-Mimetic Diphenylalanine

2021 ◽  
Author(s):  
Jacqueline L. Warren ◽  
Peter Dykeman-Bermingham ◽  
Abigail Knight
Keyword(s):  
Secondary Structure ◽  
Noncovalent Interactions ◽  
Order Structure ◽  
Amphiphilic Copolymers ◽  
Single Chain ◽  
Polymer Backbone ◽  
Systematic Analysis ◽  
Polymer Folding ◽  
The Impact ◽  
Β Sheet

While methods for polymer synthesis have proliferated, their functionality pales in comparison to natural biopolymers – strategies are limited for building the intricate network of noncovalent interactions necessary to elicit complex, protein-like functions. Using a bioinspired diphenylalanine acrylamide (FF) monomer, we explored the impact of various non-covalent interactions in generating ordered assembled structures. Amphiphilic copolymers were synthesized that exhibit β-sheet-like secondary structure upon collapsing into single-chain assemblies in aqueous environments. Systematic analysis of a series of amphiphilic copolymers illustrated that the collapse is primarily driven by hydrophobic forces. Hydrogen-bonding and aromatic interactions stabilize local structure, as β-sheet-like interactions were identified via circular dichroism and thioflavin T fluorescence. Similar analysis of phenylalanine (F) and alanine-phenylalanine acrylamide (AF) copolymers found that distancing the aromatic residue from the polymer backbone is sufficient to induce β-sheet-like secondary structure akin to the FF copolymers; however, the interactions between AF subunits are less stable than those formed by FF. Further, hydrogen-bond donating hydrophilic monomers disrupt internal structure formed by FF within collapsed assemblies. Collectively, these results illuminate design principles for the facile incorporation of multiple facets of protein-mimetic, higher-order structure within folded synthetic polymers.

scholarly journals Controlling Amphiphilic Polymer Folding Beyond the Primary Structure with Protein-Mimetic Diphenylalanine

2021 ◽  
Author(s):  
Jacqueline L. Warren ◽  
Peter Dykeman-Bermingham ◽  
Abigail Knight
Keyword(s):  
Secondary Structure ◽  
Noncovalent Interactions ◽  
Order Structure ◽  
Amphiphilic Copolymers ◽  
Single Chain ◽  
Polymer Backbone ◽  
Systematic Analysis ◽  
Polymer Folding ◽  
The Impact ◽  
Β Sheet

While methods for polymer synthesis have proliferated, their functionality pales in comparison to natural biopolymers – strategies are limited for building the intricate network of noncovalent interactions necessary to elicit complex, protein-like functions. Using a bioinspired diphenylalanine acrylamide (FF) monomer, we explored the impact of various non-covalent interactions in generating ordered assembled structures. Amphiphilic copolymers were synthesized that exhibit β-sheet-like secondary structure upon collapsing into single-chain assemblies in aqueous environments. Systematic analysis of a series of amphiphilic copolymers illustrated that the collapse is primarily driven by hydrophobic forces. Hydrogen-bonding and aromatic interactions stabilize local structure, as β-sheet-like interactions were identified via circular dichroism and thioflavin T fluorescence. Similar analysis of phenylalanine (F) and alanine-phenylalanine acrylamide (AF) copolymers found that distancing the aromatic residue from the polymer backbone is sufficient to induce β-sheet-like secondary structure akin to the FF copolymers; however, the interactions between AF subunits are less stable than those formed by FF. Further, hydrogen-bond donating hydrophilic monomers disrupt internal structure formed by FF within collapsed assemblies. Collectively, these results illuminate design principles for the facile incorporation of multiple facets of protein-mimetic, higher-order structure within folded synthetic polymers.

Exile, Diaspora, and Return

2017 ◽  
Author(s):  
Luis Roniger ◽  
Leonardo Senkman ◽  
Saúl Sosnowski ◽  
Mario Sznajder
Keyword(s):  
Systematic Analysis ◽  
The Arts ◽  
Scientific Disciplines ◽  
Early Twenty ◽  
Transnational Connections ◽  
Late Twentieth ◽  
Institutional Impact ◽  
Global Arena ◽  
Education Science ◽  
The Impact

This book explores how Argentina, Chile, Paraguay, and Uruguay have been affected by postexilic relocations, transnational migrant displacements, and diasporas. It provides a systematic analysis of the formation of exile communities and diaspora politics, the politics of return, and the agenda of democratization in the late twentieth and early twenty-first centuries, focusing on the impact of intellectuals, academics, activists, and public figures who had experienced exile on the reconstitution and transformation of their societies following democratization. Readers are offered a kaleidoscope of intellectual itineraries, debates, and contributions held in the public domain by individuals who confronted and fought authoritarian rule. The book covers their contributions to the restructuring and transformation of scientific disciplines and of the humanities and the arts, as well as their collective institutional impact on higher education, science and technology, and public institutions. Bringing together sociopolitical, cultural, and policy analysis with the testimonies of dozens of intellectuals, academics, political activists, and policymakers, the book addresses the impact of exile on people’s lives and on their fractured experiences, the debates and prospects of return, the challenges of dis-exile and postexilic trends, and, finally, the ways in which those who experienced exile impacted democratized institutions, public culture, and discourse. It also follows some crucial shifts in the frontiers of citizenship, moving analysis to transnational connections and permanent diasporas, including the diasporas of knowledge that increasingly changed the very meaning of being national and transnational, while connecting those countries to the global arena.

Assessing the Impact of Secondary Structure and Solvent Accessibility on Protein Evolution

Genetics ◽  
1998 ◽  
Vol 149 (1) ◽  
pp. 445-458 ◽  
Author(s):  
Nick Goldman ◽  
Jeffrey L Thorne ◽  
David T Jones
Keyword(s):  
Amino Acid ◽  
Secondary Structure ◽  
Protein Evolution ◽  
Solvent Accessibility ◽  
Strong Association ◽  
Length Distribution ◽  
Parametric Bootstrap ◽  
Amino Acid Replacement ◽  
Physical Constraints ◽  
The Impact

Abstract Empirically derived models of amino acid replacement are employed to study the association between various physical features of proteins and evolution. The strengths of these associations are statistically evaluated by applying the models of protein evolution to 11 diverse sets of protein sequences. Parametric bootstrap tests indicate that the solvent accessibility status of a site has a particularly strong association with the process of amino acid replacement that it experiences. Significant association between secondary structure environment and the amino acid replacement process is also observed. Careful description of the length distribution of secondary structure elements and of the organization of secondary structure and solvent accessibility along a protein did not always significantly improve the fit of the evolutionary models to the data sets that were analyzed. As indicated by the strength of the association of both solvent accessibility and secondary structure with amino acid replacement, the process of protein evolution—both above and below the species level—will not be well understood until the physical constraints that affect protein evolution are identified and characterized.

scholarly journals Solubility assessment of single-chain antibody fragment against epithelial cell adhesion molecule extracellular domain in four Escherichia coli strains

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Fatemeh Sadat Javadian ◽  
Majid Basafa ◽  
Aidin Behravan ◽  
Atieh Hashemi
Keyword(s):  
Escherichia Coli ◽  
Cell Adhesion ◽  
Epithelial Cell ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Extracellular Domain ◽  
Epithelial Cell Adhesion Molecule ◽  
Single Chain ◽  
E Coli ◽  
The Impact

Abstract Background Overexpression of the EpCAM (epithelial cell adhesion molecule) in malignancies makes it an attractive target for passive immunotherapy in a wide range of carcinomas. In comparison with full-length antibodies, due to the small size, the scFvs (single-chain variable fragments) are more suitable for recombinant expression in E. coli (Escherichia coli). However, the proteins expressed in large amounts in E. coli tend to form inclusion bodies that need to be refolded which may result in poor recovery of bioactive proteins. Various engineered strains were shown to be able to alleviate the insolubility problem. Here, we studied the impact of four E. coli strains on the soluble level of anti-EpEX-scFv (anti-EpCAM extracellular domain-scFv) protein. Results Although results showed that the amount of soluble anti-EpEX-scFv obtained in BL21TM (DE3) (114.22 ± 3.47 mg/L) was significantly higher to those produced in the same condition in E. coli RosettaTM (DE3) (71.39 ± 0.31 mg/L), and OrigamiTM T7 (58.99 ± 0.44 mg/L) strains, it was not significantly different from that produced by E. coli SHuffleTM T7 (108.87 ± 2.71 mg/L). Furthermore, the highest volumetric productivity of protein reached 318.29 ± 26.38 mg/L in BL21TM (DE3). Conclusions Although BL21TM (DE3) can be a suitable strain for high-level production of anti-EpEX-scFv protein, due to higher solubility yield (about 55%), E. coli SHuffleTM T7 seems to be better candidate for soluble production of scfv compared to BL21TM (DE3) (solubility yield of about 30%).

scholarly journals University students’ representations of Europe and self-identification as Europeans: a synthesis of qualitative evidence for future policy formulation

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Esther Cores-Bilbao ◽  
María del Carmen Méndez-García ◽  
M. Carmen Fonseca-Mora
Keyword(s):  
University Students ◽  
Evidence Synthesis ◽  
Foreign Language Learning ◽  
Educational Interventions ◽  
Policy Formulation ◽  
Qualitative Evidence Synthesis ◽  
The European Union ◽  
Systematic Analysis ◽  
Qualitative Evidence ◽  
The Impact

AbstractThe current European context is characterised by the emergence of socio-political tensions that threaten to derail the cohesion objectives traditionally promoted by the authorities of the European Union. With EU citizenship in the shadow of Brexit, the fear of dismemberment of the current Europe of the 28 looms over a renewed debate on concepts like European identity, European citizenship or EU legitimacy and the involvement of its constituents in European affairs, as well as the role of education for promoting democratic awareness among young Europeans. This work aims to collect, appraise and synthesise qualitative evidence obtained in primary research exploring the perceptions of European university students about their civic and cultural identity. This systematic analysis sets out to identify predictors of positive self-identification with the EU and its institutions, focusing on the impact that different educational interventions have had on the attitudes and perceptions expressed by university students, and the importance of foreign language learning in the results obtained. The authors report their assessment of quality of the findings in a Cochrane-style qualitative evidence synthesis (QES), based on the GRADE-CERQual (Confidence in Evidence from Reviews of Qualitative research) method. The 12 informed findings described in this study support decision-making in future education policy formulation.

scholarly journals Structural genomics approach to investigate deleterious impact of nsSNPs in conserved telomere maintenance component 1

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Arunabh Choudhury ◽  
Taj Mohammad ◽  
Nikhil Samarth ◽  
Afzal Hussain ◽  
Md. Tabish Rehman ◽  
...  
Keyword(s):  
Noncovalent Interactions ◽  
Md Simulations ◽  
Telomere Maintenance ◽  
Nucleotide Polymorphisms ◽  
Telomeric Dna ◽  
Congenital Diseases ◽  
Ob Fold ◽  
Significant Conformational Change ◽  
The Stability ◽  
The Impact

AbstractConserved telomere maintenance component 1 (CTC1) is an important component of the CST (CTC1-STN1-TEN1) complex, involved in maintaining the stability of telomeric DNA. Several non-synonymous single-nucleotide polymorphisms (nsSNPs) in CTC1 have been reported to cause Coats plus syndrome and Dyskeratosis congenital diseases. Here, we have performed sequence and structure analyses of nsSNPs of CTC1 using state-of-the-art computational methods. The structure-based study focuses on the C-terminal OB-fold region of CTC1. There are 11 pathogenic mutations identified, and detailed structural analyses were performed. These mutations cause a significant disruption of noncovalent interactions, which may be a possible reason for CTC1 instability and consequent diseases. To see the impact of such mutations on the protein conformation, all-atom molecular dynamics (MD) simulations of CTC1-wild-type (WT) and two of the selected mutations, R806C and R806L for 200 ns, were carried out. A significant conformational change in the structure of the R806C mutant was observed. This study provides a valuable direction to understand the molecular basis of CTC1 dysfunction in disease progression, including Coats plus syndrome.

Abstract P163: Global and Regional Consumption of Specific Dietary Fats and Dietary Cholesterol in 1990 and 2005: Systematic Analysis of Country-Specific Nutrition Surveys Worldwide

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Renata Micha ◽  
Shahab Khatibzadeh ◽  
Edward Giovannucci ◽  
John Powles ◽  
Peilin Shi ◽  
...  
Keyword(s):  
Chronic Diseases ◽  
Dietary Habits ◽  
Dietary Cholesterol ◽  
Assessment Method ◽  
Dietary Fats ◽  
Systematic Analysis ◽  
Diet Surveys ◽  
Nationally Representative ◽  
The Impact ◽  
Age And Sex

Background. Assessing the impact of diet on chronic diseases worldwide has been limited by availability only of food disappearance data rather than reliable and systematically assessed consumption data on dietary habits globally. Objective. To review and access published and unpublished national diet surveys worldwide in a systematic and consistent way to produce comprehensive intake data of specific dietary fats and their uncertainties by country, region, age, and sex in 1990 and 2005. Methods. We developed methods to identify, assess, and obtain exposure data (mean, SD) from nationally representative diet surveys worldwide on saturated, n-6, n-3 and trans fats, and dietary cholesterol. To address missing data and estimate mean intake, we developed and applied a multi-level hierarchical Bayesian model that accounted for country- and region-level data, measurement comparability, study representativeness, and diet assessment method. Time-varying country-level covariates were used to inform the estimates, including FAO food availability data, population, GDP, latitude, metabolic risks, and other diet covariates. Uncertainty of the estimates accounted for uncertainty from sampling and statistical modeling. Results. We obtained relevant data (85% by direct author contact) from 76 nationally representative and 15 large regional surveys from 49 countries in 15 regions, covering 75% of the world’s population. Several countries and regions lacked representative data. Data were most frequently available for saturated fat and dietary cholesterol (Figure). Results for other fats will be presented at the meeting. Conclusions. These new methods developed to systematically assess, compile and estimate the exposure distribution of specific dietary fats and cholesterol in a uniform fashion globally allow, for the first time, characterization of consumption habits and trends by country, region, age and sex. Such global assessment is imperative for estimating the impact of dietary fats on chronic diseases worldwide.

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