Structural advances of Siglecs: insight into synthetic glycan ligands for immunomodulation

2020 ◽  
Vol 18 (30) ◽  
pp. 5784-5797 ◽  
Author(s):  
Levon D. Movsisyan ◽  
Matthew S. Macauley

This review summarizes the natural and synthetic glycan ligands of Siglecs and the growing body of knowledge for structural features governing sialic acid recognition.

Author(s):  
D. F. Blake ◽  
L. F. Allard ◽  
D. R. Peacor

Echinodermata is a phylum of marine invertebrates which has been extant since Cambrian time (c.a. 500 m.y. before the present). Modern examples of echinoderms include sea urchins, sea stars, and sea lilies (crinoids). The endoskeletons of echinoderms are composed of plates or ossicles (Fig. 1) which are with few exceptions, porous, single crystals of high-magnesian calcite. Despite their single crystal nature, fracture surfaces do not exhibit the near-perfect {10.4} cleavage characteristic of inorganic calcite. This paradoxical mix of biogenic and inorganic features has prompted much recent work on echinoderm skeletal crystallography. Furthermore, fossil echinoderm hard parts comprise a volumetrically significant portion of some marine limestones sequences. The ultrastructural and microchemical characterization of modern skeletal material should lend insight into: 1). The nature of the biogenic processes involved, for example, the relationship of Mg heterogeneity to morphological and structural features in modern echinoderm material, and 2). The nature of the diagenetic changes undergone by their ancient, fossilized counterparts. In this study, high resolution TEM (HRTEM), high voltage TEM (HVTEM), and STEM microanalysis are used to characterize tha ultrastructural and microchemical composition of skeletal elements of the modern crinoid Neocrinus blakei.


2019 ◽  
Vol 16 (2) ◽  
pp. 159-172 ◽  
Author(s):  
Elaheh Kashani-Amin ◽  
Ozra Tabatabaei-Malazy ◽  
Amirhossein Sakhteman ◽  
Bagher Larijani ◽  
Azadeh Ebrahim-Habibi

Background: Prediction of proteins’ secondary structure is one of the major steps in the generation of homology models. These models provide structural information which is used to design suitable ligands for potential medicinal targets. However, selecting a proper tool between multiple Secondary Structure Prediction (SSP) options is challenging. The current study is an insight into currently favored methods and tools, within various contexts. Objective: A systematic review was performed for a comprehensive access to recent (2013-2016) studies which used or recommended protein SSP tools. Methods: Three databases, Web of Science, PubMed and Scopus were systematically searched and 99 out of the 209 studies were finally found eligible to extract data. Results: Four categories of applications for 59 retrieved SSP tools were: (I) prediction of structural features of a given sequence, (II) evaluation of a method, (III) providing input for a new SSP method and (IV) integrating an SSP tool as a component for a program. PSIPRED was found to be the most popular tool in all four categories. JPred and tools utilizing PHD (Profile network from HeiDelberg) method occupied second and third places of popularity in categories I and II. JPred was only found in the two first categories, while PHD was present in three fields. Conclusion: This study provides a comprehensive insight into the recent usage of SSP tools which could be helpful for selecting a proper tool.


Brazil constitutes a globally vital but troubled economy. It accounts for the largest GDP in Latin America and ranks among the world’s largest exporters of critical commodities including iron ore, soya, coffee, and beef. In recent years Brazil’s global economic importance has been magnified by a surge in both outward and inward foreign direct investment. This has served to further internationalize what has been historically a relatively closed economy. The purpose of this Handbook is to offer real insight into the Brazil’s economic development in contemporary context, understanding its most salient characteristics and analyzing its structural features across various dimensions. At a more granular level, this volume accomplishes the following tasks. First, it provides an understanding of the economy’s evolution over time and the connection of its current characteristics to this evolution. Second, it analyzes Brazil’s broader place in the global economy, and considers the ways in which this role has changed, and is likely to change, over coming years. Third, reflecting contemporary concerns, the volume offers an understanding, not only of how one of the world’s key economies has developed and transformed itself, but also of the ways in which this process has yet to be completed. The volume thus analyzes the current challenges facing the Brazilian economy and the kinds of issues that need to be tackled for these to be addressed.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Qiuye Li ◽  
W. Michael Babinchak ◽  
Witold K. Surewicz

AbstractAmyotrophic lateral sclerosis and several other neurodegenerative diseases are associated with brain deposits of amyloid-like aggregates formed by the C-terminal fragments of TDP-43 that contain the low complexity domain of the protein. Here, we report the cryo-EM structure of amyloid formed from the entire TDP-43 low complexity domain in vitro at pH 4. This structure reveals single protofilament fibrils containing a large (139-residue), tightly packed core. While the C-terminal part of this core region is largely planar and characterized by a small proportion of hydrophobic amino acids, the N-terminal region contains numerous hydrophobic residues and has a non-planar backbone conformation, resulting in rugged surfaces of fibril ends. The structural features found in these fibrils differ from those previously found for fibrils generated from short protein fragments. The present atomic model for TDP-43 LCD fibrils provides insight into potential structural perturbations caused by phosphorylation and disease-related mutations.


Fuel ◽  
2015 ◽  
Vol 153 ◽  
pp. 176-182 ◽  
Author(s):  
Zhan-Ku Li ◽  
Xian-Yong Wei ◽  
Hong-Lei Yan ◽  
Zhi-Min Zong

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Qin Gong ◽  
Kim Robinson ◽  
Chenrui Xu ◽  
Phuong Thao Huynh ◽  
Kelvin Han Chung Chong ◽  
...  

AbstractNod-like receptor (NLR) proteins activate pyroptotic cell death and IL-1 driven inflammation by assembling and activating the inflammasome complex. Closely related sensor proteins NLRP1 and CARD8 undergo unique auto-proteolysis-dependent activation and are implicated in auto-inflammatory diseases; however, their mechanisms of activation are not understood. Here we report the structural basis of how the activating domains (FIINDUPA-CARD) of NLRP1 and CARD8 self-oligomerize to assemble distinct inflammasome complexes. Recombinant FIINDUPA-CARD of NLRP1 forms a two-layered filament, with an inner core of oligomerized CARD surrounded by an outer ring of FIINDUPA. Biochemically, self-assembled NLRP1-CARD filaments are sufficient to drive ASC speck formation in cultured human cells—a process that is greatly enhanced by NLRP1-FIINDUPA which forms oligomers in vitro. The cryo-EM structures of NLRP1-CARD and CARD8-CARD filaments, solved here at 3.7 Å, uncover unique structural features that enable NLRP1 and CARD8 to discriminate between ASC and pro-caspase-1. In summary, our findings provide structural insight into the mechanisms of activation for human NLRP1 and CARD8 and reveal how highly specific signaling can be achieved by heterotypic CARD interactions within the inflammasome complexes.


1992 ◽  
Vol 16 (4) ◽  
pp. 415-428 ◽  
Author(s):  
Cynthia L. Miller ◽  
A. Gaye Cummins

Historically, theoretical and popular conceptions about power have not included or addressed women's experiences. This study adds to the growing body of knowledge about women by examining women's perceptions of and relationship to power. One hundred twenty-five women, ranging in age from 21 to 63, were asked to define and explore power through a variety of structured and open-ended questions. The results showed that women's definition of power differed significantly from their perception of society's definition of power, as well as from the way power has traditionally been conceptualized. More theoretical and empirical attention should be given to understanding the role of personal authority in both women's and men's experience of power.


2002 ◽  
Vol 12 (3) ◽  
pp. 201-207 ◽  
Author(s):  
Cynthia L. Russell ◽  
Kristi Brown

Context No empirical studies exist to direct nursing interventions for individuals during the long period of waiting for a transplant. Objective To measure the effect of information and support on hope and uncertainty for individuals awaiting cadaveric kidney transplantation. Design Randomized, controlled study. Setting A university-affiliated hospital in the Midwest from 1997 to 1999. Patients Fifty participants awaiting cadaveric kidney transplantation. Interventions The control group received no intervention phone calls or mailings, which was the current standard of care. The treatment group received phone calls and mailings once every month for 6 months. Main Outcome Measures Hope, measured by the Herth Hope Index, and uncertainty, measured by the Mishel's Uncertainty in Illness Scale for Adults, were evaluated at the beginning of the study and 6 months later. Results No statistically significant effect of the nursing intervention was found on hope and uncertainty in this sample (F = 0.5322, P = .81). Hope was found to be negatively related to uncertainty both before ( r = $0.53, P = .0001) and after ( r = $0.59, P = .0001) intervention. No significant change was found between hope before and after intervention, and uncertainty before and after intervention in the treatment group (F = 1.10, P = .40) or the control group. Conclusion The individuals indicated that definite needs were met by the information and support intervention even though the results did not statistically support the effect of the nursing intervention. Conclusions Several conclusions can be drawn from the findings of this study. First, even though the nursing intervention of providing information and support did not have a statistically significant effect on levels of hope and uncertainty in individuals awaiting kidney transplantation, anecdotal reports from the respondents indicated that the phone calls and mailed information were helpful and appreciated. Valuable information, potentially impacting the outcomes of kidney transplantation, was gathered by the researchers and shared with the transplant team. Secondly, levels of hope were relatively high, whereas levels of uncertainty were moderate in this sample of individuals waiting for cadaveric kidney transplantation. Furthermore, in this sample, the average time since diagnosis of ESRD was more than 4 years and the average waiting time was more than 1 year. There may have been a change over time from viewing the waiting experience as a negative experience to a positive opportunity. Thirdly, the finding of a negative relationship between hope and uncertainty provided support to the growing body of knowledge of this association. Finally, time on the waiting list, gender, and marital status were not associated with levels of hope or uncertainty. Generally, the findings of this study are consistent with existing literature and add to the growing body of knowledge related to the midrange theories of hope and uncertainty.


2018 ◽  
Vol 19 (12) ◽  
pp. 3858
Author(s):  
Milan Hodošček ◽  
Nadia Elghobashi-Meinhardt

A combination of molecular dynamics (MD) simulations and computational analyses uncovers structural features that may influence substrate passage and exposure to the active sites within the proteolytic chamber of the 20S proteasome core particle (CP). MD simulations of the CP reveal relaxation dynamics in which the CP slowly contracts over the 54 ns sampling period. MD simulations of the SyringolinA (SylA) inhibitor within the proteolytic B 1 ring chamber of the CP indicate that favorable van der Waals and electrostatic interactions account for the predominant association of the inhibitor with the walls of the proteolytic chamber. The time scale required for the inhibitor to travel from the center of the proteolytic chamber to the chamber wall is on the order of 4 ns, accompanied by an average energetic stabilization of approximately −20 kcal/mol.


Blood ◽  
2010 ◽  
Vol 115 (13) ◽  
pp. 2569-2577 ◽  
Author(s):  
Jonas Emsley ◽  
Paul A. McEwan ◽  
David Gailani

AbstractFactor XI (FXI) is the zymogen of an enzyme (FXIa) that contributes to hemostasis by activating factor IX. Although bleeding associated with FXI deficiency is relatively mild, there has been resurgence of interest in FXI because of studies indicating it makes contributions to thrombosis and other processes associated with dysregulated coagulation. FXI is an unusual dimeric protease, with structural features that distinguish it from vitamin K–dependent coagulation proteases. The recent availability of crystal structures for zymogen FXI and the FXIa catalytic domain have enhanced our understanding of structure-function relationships for this molecule. FXI contains 4 “apple domains” that form a disk structure with extensive interfaces at the base of the catalytic domain. The characterization of the apple disk structure, and its relationship to the catalytic domain, have provided new insight into the mechanism of FXI activation, the interaction of FXIa with the substrate factor IX, and the binding of FXI to platelets. Analyses of missense mutations associated with FXI deficiency have provided additional clues to localization of ligand-binding sites on the protein surface. Together, these data will facilitate efforts to understand the physiology and pathology of this unusual protease, and development of therapeutics to treat thrombotic disorders.


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