scholarly journals Microgel Particles with Distinct Morphologies and Common Chemical Compositions: A Unified Description of the Responsivity to Temperature and Osmotic Stress

Gels ◽  
2020 ◽  
Vol 6 (4) ◽  
pp. 34
Author(s):  
Andrea Ruscito ◽  
Ester Chiessi ◽  
Yosra Toumia ◽  
Letizia Oddo ◽  
Fabio Domenici ◽  
...  

Poly(N-isopropylacrylamide) (PNIPAM) hydrogel microparticles with different core–shell morphologies have been designed, while maintaining an unvaried chemical composition: a morphology with (i) an un-crosslinked core with a crosslinked shell of PNIPAM chains and (ii) PNIPAM chains crosslinked to form the core with a shell consisting of tethered un-crosslinked PNIPAM chains to the core. Both morphologies with two different degrees of crosslinking have been assessed by confocal microscopy and tested with respect to their temperature responsivity and deformation by applying an osmotic stress. The thermal and mechanical behavior of these architectures have been framed within a Flory–Rehner modified model in order to describe the microgel volume shrinking occurring as response to a temperature increase or an osmotic perturbation. This study provides a background for assessing to what extent the mechanical features of the microgel particle surface affect the interactions occurring at the interface of a microgel particle with a cell, in addition to the already know ligand/receptor interaction. These results have direct implications in triggering a limited phagocytosis of microdevices designed as injectable drug delivery systems.

2019 ◽  
Vol 7 ◽  
pp. 124-141
Author(s):  
Kimberley Kroll

In 2014, Ray Yeo published a modified account of the Spirit’s indwelling in “Towards a Model of the Indwelling: A Conversation with Jonathan Edwards and William Alston.” Yeo utilizes a conglomerate of Two-Minds Christology and Spirit Christology to provide a metaphysical framework for his model which he believes offers a viable alternative to more traditional merger accounts like those of Edwards and Alston. After providing an overview of Yeo’s objections to the merger accounts of Alston and Edwards, I will summarize Yeo’s modified model. I will argue Yeo’s emphasis on the humanity of Christ in lieu of a literal, internal, and direct union of the Holy Spirit and the human person cannot alleviate the core metaphysical concerns which surface in all accounts of union between the divine and human.  Yeo’s misunderstanding of Two-Minds Christology leads him to deny the full humanity of Christ; a humanity upon which his entire account of the indwelling relies. Yeo’s modified model will be shown unsuccessful as an account of the indwelling of the Holy Spirit even if one accepts both his conception of Two-Minds Christology and his conditions for indwelling.


Author(s):  
Fen Wei ◽  
Xiaxi Zhang ◽  
Ping Cui ◽  
Xilan Gou ◽  
Sicen Wang

A cell-based screening method for drug lead target capture using a microcarrier covered with highly expressed receptor cells as a 3D biomimetic framework.


2010 ◽  
Vol 98 (3) ◽  
pp. 161a-162a
Author(s):  
Yee Seir Kee ◽  
Richard Firtel ◽  
Pablo Iglesias ◽  
Douglas Robinson

2015 ◽  
Vol 90 (5) ◽  
pp. 2294-2305 ◽  
Author(s):  
Eric P. Schultz ◽  
Jean-Marc Lanchy ◽  
Erin E. Ellerbeck ◽  
Brent J. Ryckman

ABSTRACTThe core, conserved function of the herpesvirus gH/gL is to promote gB-mediated membrane fusion during entry, although the mechanism is poorly understood. The human cytomegalovirus (HCMV) gH/gL can exist as either the gH/gL/gO trimer or the gH/gL/UL128/UL130/UL131 (gH/gL/UL128-131) pentamer. One model suggests that gH/gL/gO provides the core fusion role during entry into all cells within the broad tropism of HCMV, whereas gH/gL/UL128-131 acts at an earlier stage, by a distinct receptor-binding mechanism to enhance infection of select cell types, such as epithelial cells, endothelial cells, and monocytes/macrophages. To further study the distinct functions of these complexes, mutants with individual charged cluster-to-alanine (CCTA) mutations of gH and gL were combined to generate a library of 80 mutant gH/gL heterodimers. The majority of the mutant gH/gL complexes were unable to facilitate gB-mediated membrane fusion in transient-expression cell-cell fusion experiments. In contrast, these mutants supported the formation of gH/gL/UL128-131 complexes that could block HCMV infection in receptor interference experiments. These results suggest that receptor interactions with gH/gL/UL128-131 involve surfaces contained on the UL128-131 proteins but not on gH/gL. gH/gL/UL128-131 receptor interference could be blocked with anti-gH antibodies, suggesting that interference is a cell surface phenomenon and that anti-gH antibodies can block gH/gL/UL128-131 in a manner that is distinct from that for gH/gL/gO.IMPORTANCEInterest in the gH/gL complexes of HCMV (especially gH/gL/UL128-131) as vaccine targets has far outpaced our understanding of the mechanism by which they facilitate entry and contribute to broad cellular tropism. For Epstein-Barr virus (EBV), gH/gL and gH/gL/gp42 are both capable of promoting gB fusion for entry into epithelial cells and B cells, respectively. In contrast, HCMV gH/gL/gO appears to be the sole fusion cofactor that promotes gB fusion activity, whereas gH/gL/UL128-131 expands cell tropism through a distinct yet unknown mechanism. This study suggests that the surfaces of HCMV gH/gL are critical for promoting gB fusion but are dispensable for gH/gL/UL128-131 receptor interaction. This underscores the importance of gH/gL/gO in HCMV entry into all cell types and reaffirms the complex as a candidate target for vaccine development. The two functionally distinct forms of gH/gL present in HCMV make for a useful model with which to study the fundamental mechanisms by which herpesvirus gH/gL regulates gB fusion.


Virology ◽  
1981 ◽  
Vol 108 (1) ◽  
pp. 147-155 ◽  
Author(s):  
Edward C. Hayes ◽  
Patrick W.K. Lee ◽  
Sara E. Miller ◽  
Wolfgang K. Joklik

2010 ◽  
Vol 298 (2) ◽  
pp. R254-R260 ◽  
Author(s):  
Stephanie W. Watts

Receptors are at the heart of how a molecule transmits a signal to a cell. Two receptor classes for endothelin (ET) are recognized, the ETAand ETBreceptors. Intriguing questions have arisen in the field of ET receptor pharmacology, physiology, and function. For example, a host of pharmacological studies support the interaction of the ETAand ETBreceptor in tissues (veins, arteries, bronchus, arterioles, esophagus), but yet few have been able to demonstrate direct ETA/ETBreceptor interaction. Have we modeled this interaction wrong? Do we have a truly selective ETAreceptor agonist such that we could selectively stimulate this important receptor? What can we learn from the recent phylogenic studies of the ET receptor family? Have we adequately addressed the number of biological molecules with which ET can interact to exert a biological effect? Recent mass spectrometry studies in our laboratory suggest that ET-1 interacts with other hereto unrecognized proteins. Biased ligands (ligands at the same receptor that elicit distinct signaling responses) have been discovered for other receptors. Do these exist for ET receptors and can we take advantage of this possibility in drug design? These and other questions will be posed in this minireview on topics on ET receptors.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
İbrahim Avşar Ilik ◽  
Michal Malszycki ◽  
Anna Katharina Lübke ◽  
Claudia Schade ◽  
David Meierhofer ◽  
...  

Nuclear speckles (NS) are among the most prominent biomolecular condensates. Despite their prevalence, research on the function of NS is virtually restricted to colocalization analyses, since an organizing core, without which NS cannot form, remains unidentified. The monoclonal antibody SC35, raised against a spliceosomal extract, is frequently used to mark NS. Unexpectedly, we found that this antibody was mischaracterized and the main target of SC35 mAb is SRRM2, a spliceosome-associated protein that sharply localizes to NS. Here we show that, the core of NS is likely formed by SON and SRRM2, since depletion of SON leads only to a partial disassembly of NS, while co-depletion of SON and SRRM2 or depletion of SON in a cell-line where intrinsically disordered regions (IDRs) of SRRM2 are genetically deleted, leads to a near-complete dissolution of NS. This work, therefore, paves the way to study the role of NS under diverse physiological and stress conditions.


2001 ◽  
Vol 82 (3) ◽  
pp. 547-559 ◽  
Author(s):  
Mojgan H. Naghavi ◽  
Mario C. Estable ◽  
Stefan Schwartz ◽  
Robert G. Roeder ◽  
Anders Vahlne

Human immunodeficiency virus type 1 (HIV-1) is classified into subtypes on the basis of phylogenetic analysis of sequence differences. Inter- and intra-subtype polymorphism extends throughout the genome, including the long terminal repeat (LTR). In this study, the importance of the upstream stimulating factor (USF)-binding site (E-box) in the core-negative regulatory element (NRE) of the LTR of HIV-1 subtypes A, B, C, D, E and G was investigated. In vivo, USF was found to repress transcription directed from representative HIV-1 LTR sequences of all the subtypes tested in an epithelial cell line, yet activate the same transcription in a T-cell line. Mutation of the core-NRE USF site of the representative subtype B LTR did not affect the cell-specific, subtype-independent, dual role of USF. In vitro binding assays showed that recombinant USF43 interacts with the core-NRE from subtypes B and C, but not A, D, E or G. Thus, USF affects LTR-directed transcription in a cell-specific manner, independently of both the HIV-1 subtype from which the LTR was derived and the core-NRE USF site sequences.


2009 ◽  
Vol 132 (2) ◽  
Author(s):  
Leonid A. Dombrovsky

The recently developed model for thermal radiation in multiphase flows typical of melt-coolant interactions is generalized to account for transient temperature profile in large semitransparent particles of solidifying melt. A modification of the large-cell radiation model (LCRM) is based on the approximate solution for coupled radiation and conduction in optically thick spherical particles of a refractive material. The simplicity of the suggested approximation enables one to implement the modified model in a multiphase computational fluid dynamics code. The LCRM extension makes possible the use of this approach not only for the core melt in nuclear fuel-coolant interactions but also for other melt substances, which are widely used in the laboratory experiments. The numerical data demonstrate an effect of absorption coefficient of the particle substance on the rate of particle cooling and solidification.


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