scholarly journals Structural and cellular insights into the L,D-transpeptidase YcbB as a therapeutic target in C. rodentium, S. Typhimurium, and S. Typhi infections

2020 ◽  
Author(s):  
N A Caveney ◽  
A Serapio-Palacios ◽  
S E Woodward ◽  
T Bozorgmehr ◽  
G Caballero ◽  
...  
Keyword(s):  
Cell Wall ◽  
Structural Characteristics ◽  
General Role ◽  
Acute Infections ◽  
Envelope Stress ◽  
Crystallographic Structures ◽  
Host Infection ◽  
Typhoid Toxin ◽  
Important Drug

The bacterial cell wall plays a key role in viability and is an important drug target. The cell wall is made of elongated polymers that are crosslinked to one another to form a load bearing mesh. An alternate cell wall crosslinking mechanism performed by the L,D-transpeptidase YcbB has been implicated in the stress regulated roles of β-lactam resistance, outer membrane defect rescue, and typhoid toxin release. The role for this stress linked crosslinking in the context of a host infection was unclear. Here we resolve the crystallographic structures of both S. Typhi YcbB and C. rodentium YcbB acylated with ertapenem that delineate the conserved structural characteristics of YcbB. In parallel, we show that the general role of YcbB in peptidoglycan reinforcement under bacterial outer envelope stress does not play a significant role in acute infections of mice by C. rodentium and S. Typhimurium. Cumulatively, in this work we provide a foundation for the development of novel YcbB specific antibacterial therapeutics to assist in treatment of increasingly drug resistant S. Typhi infections.

Role of the Structural Characteristics of Dendrimers in the Manifestation of the Antiamyloid Properties

INEOS OPEN ◽  
2020 ◽  
Vol 3 ◽  
Author(s):  
S. A. Sorokina ◽  
◽  
Yu. Yu. Stroilova ◽  
V. I. Muronets ◽  
Z. B. Shifrina ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Structural Characteristics ◽  
Short Review ◽  
External Factors ◽  
Amyloid Aggregation ◽  
Amyloid Proteins ◽  
Molecular Parameters ◽  
Amyloid Aggregates ◽  
Aggregation Processes

Among the compounds able to efficiently inhibit the amyloid aggregation of proteins and decompose the amyloid aggregates that cause neurodegenerative diseases, of particular interest are dendrimers, which represent individual macromolecules with the hypercrosslinked architectures and given molecular parameters. This short review outlines the peculiarities of the antiamyloid activity of dendrimers and discusses the effect of dendrimer structures and external factors on their antiamyloid properties. The potential of application of dendrimers in further investigations on the aggregation processes of amyloid proteins as the compounds that exhibit the remarkable antiamyloid activity is evaluated.

СТРУКТУРА, МОДЕЛИ И СТРАТЕГИИ УЧАСТИЯ ГОРОДСКИХ СООБЩЕСТВ В КОНФЛИКТАХ

2020 ◽  
Vol 15 (2) ◽  
pp. 54
Author(s):  
А. И. Кольба ◽  
Н. В. Кольба
Keyword(s):  
Political Parties ◽  
Urban Communities ◽  
Municipal Government ◽  
Structural Characteristics ◽  
City Government ◽  
Expert Interviews ◽  
Competitive Strategies ◽  
Scientific Publications ◽  
The City

The article describes the structural characteristics of the urban communities of the city of Krasnodar and the related features that impact their participation in urban conflicts. This issue is considered in a number of scientific publications, but there is a need to expand the empirical base of such studies. On the base of expert interviews conducted with both city activists, their counterparty (representatives of the municipal government) and external observers (journalists), the parameters of urban communities functioning in the process of their interaction with other conflict actors are revealed. The communities characteristics such as the predominantly territorial principle of formation, the overlap of online and offline communications in their activities, the presence of a “core” with a relatively low number of permanent participants and others are determined. Their activities are dominated by neighborly and civilian models of participation in conflicts. The possibilities of realizing one’s own interests through political interactions (participation in elections, the activities of representative bodies of power, political parties) are not yet sufficiently understood. Urban communities, as a rule, operate within the framework of conventional forms of participation in solving urgent problems, although in some cases it is possible to use confrontational methods, in particular, protest ones. In this regard, the most often used compromise, with the desire for cooperation, a strategy of behavior in interaction with opponents. The limited activating role of conflicts in the activities of communities has been established. The weak manifestation of the civil and especially political component in their activities determines the preservation of a low level of political subjectivity. This factor restrains the growth of urban communities resources and the possibility of applying competitive strategies in interaction with city government and business.

Role of bacterial cell wall proteinase in antihypertension

2002 ◽  
Vol 22 (1-2) ◽  
pp. 209-222 ◽  
Author(s):  
Bénédicte Flambard
Keyword(s):  
Cell Wall ◽  
Bacterial Cell ◽  
Bacterial Cell Wall

Dissent in the Atlantic World, 1787–1830

2018 ◽  
Author(s):  
Katherine Carté Engel
Keyword(s):  
United States ◽  
African Americans ◽  
First Amendment ◽  
Church And State ◽  
State Level ◽  
The United States ◽  
American Population ◽  
Simple Fact ◽  
General Role

The very term ‘Dissenter’ became problematic in the United States, following the passing of the First Amendment. The formal separation of Church and state embodied in the First Amendment was followed by the ending of state-level tax support for churches. None of the states established after 1792 had formal religious establishments. Baptists, Congregationalists, Presbyterians, and Methodists accounted for the majority of the American population both at the beginning and end of this period, but this simple fact masks an important compositional shift. While the denominations of Old Dissent declined relatively, Methodism grew quickly, representing a third of the population by 1850. Dissenters thus faced several different challenges. Primary among these were how to understand the idea of ‘denomination’ and also the more general role of institutional religion in a post-establishment society. Concerns about missions, and the positions of women and African Americans are best understood within this context.

scholarly journals An R2R3-type myeloblastosis transcription factor MYB103 is involved in phosphorus remobilization

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Fangwei Yu ◽  
Shenyun Wang ◽  
Wei Zhang ◽  
Hong Wang ◽  
Li Yu ◽  
...  
Keyword(s):  
Cell Wall ◽  
Transcription Factor ◽  
Abiotic Stresses ◽  
Myb Transcription Factor ◽  
Ethylene Signaling ◽  
Biotic And Abiotic Stresses ◽  
P Deficiency ◽  
P Concentration ◽  
Increased Sensitivity

Abstract The members of myeloblastosis transcription factor (MYB TF) family are involved in the regulation of biotic and abiotic stresses in plants. However, the role of MYB TF in phosphorus remobilization remains largely unexplored. In the present study, we show that an R2R3 type MYB transcription factor, MYB103, is involved in phosphorus (P) remobilization. MYB103 was remarkably induced by P deficiency in cabbage (Brassica oleracea var. capitata L.). As cabbage lacks the proper mutant for elucidating the mechanism of MYB103 in P deficiency, another member of the crucifer family, Arabidopsis thaliana was chosen for further study. The transcript of its homologue AtMYB103 was also elevated in response to P deficiency in A. thaliana, while disruption of AtMYB103 (myb103) exhibited increased sensitivity to P deficiency, accompanied with decreased tissue biomass and soluble P concentration. Furthermore, AtMYB103 was involved in the P reutilization from cell wall, as less P was released from the cell wall in myb103 than in wildtype, coinciding with the reduction of ethylene production. Taken together, our results uncover an important role of MYB103 in the P remobilization, presumably through ethylene signaling.

scholarly journals Tethering-induced destabilization and ATP-binding for tandem RRM domains of ALS-causing TDP-43 and hnRNPA1

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mei Dang ◽  
Yifan Li ◽  
Jianxing Song
Keyword(s):  
Conformational Dynamics ◽  
Md Simulations ◽  
Atp Binding ◽  
Rna Recognition Motif ◽  
Rna Recognition ◽  
Nucleic Acid Binding ◽  
General Role ◽  
Nmr Characterization ◽  
Lateral Sclerosis

AbstractTDP-43 and hnRNPA1 contain tandemly-tethered RNA-recognition-motif (RRM) domains, which not only functionally bind an array of nucleic acids, but also participate in aggregation/fibrillation, a pathological hallmark of various human diseases including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), alzheimer's disease (AD) and Multisystem proteinopathy (MSP). Here, by DSF, NMR and MD simulations we systematically characterized stability, ATP-binding and conformational dynamics of TDP-43 and hnRNPA1 RRM domains in both tethered and isolated forms. The results reveal three key findings: (1) upon tethering TDP-43 RRM domains become dramatically coupled and destabilized with Tm reduced to only 49 °C. (2) ATP specifically binds TDP-43 and hnRNPA1 RRM domains, in which ATP occupies the similar pockets within the conserved nucleic-acid-binding surfaces, with the affinity slightly higher to the tethered than isolated forms. (3) MD simulations indicate that the tethered RRM domains of TDP-43 and hnRNPA1 have higher conformational dynamics than the isolated forms. Two RRM domains become coupled as shown by NMR characterization and analysis of inter-domain correlation motions. The study explains the long-standing puzzle that the tethered TDP-43 RRM1–RRM2 is particularly prone to aggregation/fibrillation, and underscores the general role of ATP in inhibiting aggregation/fibrillation of RRM-containing proteins. The results also rationalize the observation that the risk of aggregation-causing diseases increases with aging.

scholarly journals Thiophene-Based Compounds with Potential Anti-Inflammatory Activity

2021 ◽  
Vol 14 (7) ◽  
pp. 692
Author(s):  
Ryldene Marques Duarte da Cruz ◽  
Francisco Jaime Bezerra Mendonça-Junior ◽  
Natália Barbosa de Mélo ◽  
Luciana Scotti ◽  
Rodrigo Santos Aquino de Araújo ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Structural Characteristics ◽  
Tiaprofenic Acid ◽  
Inflammatory Activity ◽  
Drug Candidates ◽  
Biological Target ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Privileged Structures

Rheumatoid arthritis, arthrosis and gout, among other chronic inflammatory diseases are public health problems and represent major therapeutic challenges. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most prescribed clinical treatments, despite their severe side effects and their exclusive action in improving symptoms, without effectively promoting the cure. However, recent advances in the fields of pharmacology, medicinal chemistry, and chemoinformatics have provided valuable information and opportunities for development of new anti-inflammatory drug candidates. For drug design and discovery, thiophene derivatives are privileged structures. Thiophene-based compounds, like the commercial drugs Tinoridine and Tiaprofenic acid, are known for their anti-inflammatory properties. The present review provides an update on the role of thiophene-based derivatives in inflammation. Studies on mechanisms of action, interactions with receptors (especially against cyclooxygenase (COX) and lipoxygenase (LOX)), and structure-activity relationships are also presented and discussed. The results demonstrate the importance of thiophene-based compounds as privileged structures for the design and discovery of novel anti-inflammatory agents. The studies reveal important structural characteristics. The presence of carboxylic acids, esters, amines, and amides, as well as methyl and methoxy groups, has been frequently described, and highlights the importance of these groups for anti-inflammatory activity and biological target recognition, especially for inhibition of COX and LOX enzymes.

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