scholarly journals Tuning of Differential Lipid Order Between Submicrometric Domains and Surrounding Membrane Upon Erythrocyte Reshaping

2018 ◽  
Vol 48 (6) ◽  
pp. 2563-2582 ◽  
Author(s):  
Catherine Leonard ◽  
Hélène Pollet ◽  
Christiane Vermylen ◽  
Nir Gov ◽  
Donatienne Tyteca ◽  
...  
Keyword(s):  
Critical Role ◽  
Lipid Domains ◽  
Generalized Polarization ◽  
Lipid Order ◽  
Imaging Mode ◽  
Erythrocyte Deformation ◽  
Membrane Vesiculation ◽  
The Difference ◽  
Surrounding Membrane

Background/Aims: Transient nanometric cholesterol- and sphingolipid-enriched domains, called rafts, are characterized by higher lipid order as compared to surrounding lipids. Here, we asked whether the seminal concept of highly ordered rafts could be refined with the presence of lipid domains exhibiting different enrichment in cholesterol and sphingomyelin and association with erythrocyte curvature areas. We also investigated how differences in lipid order between domains and surrounding membrane (bulk) are regulated and whether changes in order differences could participate to erythrocyte deformation and vesiculation. Methods: We used the fluorescent hydration- and membrane packing-sensitive probe Laurdan to determine by imaging mode the Generalized Polarization (GP) values of lipid domains vs the surrounding membrane. Results: Laurdan revealed the majority of sphingomyelin-enriched domains associated to low erythrocyte curvature areas and part of the cholesterol-enriched domains associated with high curvature. Both lipid domains were less ordered than the surrounding lipids in erythrocytes at resting state. Upon erythrocyte deformation (elliptocytes and stimulation of calcium exchanges) or membrane vesiculation (storage at 4°C), lipid domains became more ordered than the bulk. Upon aging and in membrane fragility diseases (spherocytosis), an increase in the difference of lipid order between domains and the surrounding lipids contributed to the initiation of domain vesiculation. Conclusion: The critical role of domain-bulk differential lipid order modulation for erythrocyte reshaping is discussed in relation with the pressure exerted by the cytoskeleton on the membrane.

Implementing the Team Approach in Higher Education

2008 ◽  
Vol 22 (4) ◽  
pp. 245-251 ◽  
Author(s):  
Tracy M. Lara ◽  
Aaron W. Hughey
Keyword(s):  
Higher Education ◽  
Needs Assessment ◽  
Higher Education Administration ◽  
Critical Role ◽  
Education Administration ◽  
Team Approach ◽  
Academic Environment ◽  
Team Efficacy ◽  
The Difference

Many companies have implemented the team approach as a way to empower their employees in an effort to enhance productivity, quality and overall profitability. While application of the concept to higher education administration has been limited, colleges and universities could benefit from the team approach if implemented appropriately and conscientiously. The authors discuss some of the issues and concerns that are relevant to implementing the team approach in an academic environment. Suggestions for implementing teams in higher education are provided, including the difference between the team approach and traditional administration, the importance of a preliminary needs assessment, the development of an implementation plan, the critical role of leadership, dealing with issues of assessment and accountability, and the concept of team efficacy.

scholarly journals Critical Negatively Charged Residues Are Important for the Activity of SARS-CoV-1 and SARS-CoV-2 Fusion Peptides

2021 ◽  
Author(s):  
Alex L. Lai ◽  
Jack H. Freed
Keyword(s):  
Critical Role ◽  
Binding Energies ◽  
Host Cells ◽  
Topological Model ◽  
Pseudotyped Virus ◽  
Fusion Peptides ◽  
Human Pathogens ◽  
Charged Residues ◽  
The Difference

AbstractCoronaviruses are a major infectious disease threat, and include the human pathogens of zoonotic origin SARS-CoV (“SARS-1”), SARS-CoV-2 (“SARS-2”) and MERS-CoV (“MERS”). Entry of coronaviruses into host cells is mediated by the viral spike (S) protein. Previously, we identified that the domain immediately downstream of the S2’ cleavage site is the bona fide FP (amino acids 798-835) for SARS-1 using ESR spectroscopy technology. We also found that the SARS-1 FP induces membrane ordering in a Ca2+ dependent fashion. In this study, we want to know which residues are involved in this Ca2+ binding, to build a topological model and to understand the role of the Ca2+. We performed a systematic mutation study on the negatively charged residues on the SARS-1 FP. While all six negatively charged residues contributes to the membrane ordering activity of the FP to some extent, D812 is the most important residue. We provided a topological model of how the FP binds Ca2+ ions: both FP1 and FP2 bind one Ca2+ ion, and there are two binding sites in FP1 and three in FP2. We also found that the corresponding residue D830 in the SARS-2 FP plays a similar critical role. ITC experiments show that the binding energies between the FP and Ca2+ as well as between the FP and membranes also decreases for all mutants. The binding of Ca2+, the folding of FP and the ordering activity correlated very well across the mutants, suggesting that the function of the Ca2+ is to help to folding of FP in membranes to enhance its activity. Using a novel pseudotyped virus particle (PP)-liposome methodology, we monitored the membrane ordering induced by the FPs in the whole S proteins in its trimer form in real time. We found that the SARS-1 and SARS-2 PPs also induce membrane ordering as the separate FPs do, and the mutations of the negatively charged residues also greatly reduce the membrane ordering activity. However, the difference in kinetic between the PP and FP indicates a possible role of FP trimerization. This finding could lead to therapeutic solutions that either target the FP-calcium interaction or block the Ca2+ channel to combat the ongoing COVID-19 pandemic.

scholarly journals Updated SARS-CoV-2 Single Nucleotide Variants and Mortality Association

2021 ◽  
Author(s):  
Shuyi Fang ◽  
Sheng Liu ◽  
Jikui Shen ◽  
Alex Z Lu ◽  
Yucheng Zhang ◽  
...  
Keyword(s):  
Protein Structure ◽  
Critical Role ◽  
Single Nucleotide Variants ◽  
Protein Structure Analysis ◽  
Single Nucleotide ◽  
Synonymous Mutations ◽  
Conformation Changes ◽  
The Difference ◽  
Distinct Distribution

AbstractSince its outbreak in December 2019, COVID-19 has caused 100,5844,555 cases and 2,167,313 deaths as of Jan 27, 2021. Comparing our previous study of SARS-CoV-2 single nucleotide variants (SNVs) before June 2020, we found out that the SNV clustering had changed considerably since June 2020. Apart from that the group SNVs represented by two non-synonymous mutations A23403G (S: D614G) and C14408T (ORF1ab: P4715L) became dominant and carried by over 95% genomes, a few emerging groups of SNVs were recognized with sharply increased monthly occurrence ratios up to 70% in November 2020. Further investigation revealed that several SNVs were strongly associated with the mortality, but they presented distinct distribution in specific countries, e.g., Brazil, USA, Saudi Arabia, India, and Italy. SNVs including G25088T, T25A, G29861T and G29864A were adopted in a regularized logistic regression model to predict the mortality status in Brazil with the AUC of 0.84. Protein structure analysis showed that the emerging subgroups of non-synonymous SNVs and those mortality-related ones in Brazil were located on protein surface area. The clashes in protein structure introduced by these mutations might in turn affect virus pathogenesis through conformation changes, leading to the difference in transmission and virulence. Particularly, we found that SNVs tended to occur in intrinsic disordered regions (IDRs) of Spike (S) and ORF1ab, suggesting a critical role of SNVs in protein IDRs to determine protein folding and immune evasion.

scholarly journals A Critical Role of Non-active Site Residues on Cyclooxygenase Helices 5 and 6 in the Control of Prostaglandin Stereochemistry at Carbon 15

2007 ◽  
Vol 282 (38) ◽  
pp. 28157-28163 ◽  
Author(s):  
Karin Valmsen ◽  
William E. Boeglin ◽  
Reet Järving ◽  
Ivar Järving ◽  
Külliki Varvas ◽  
...  
Keyword(s):  
Amino Acid ◽  
Active Site ◽  
Amino Acid Sequence Identity ◽  
Critical Role ◽  
Site Directed Mutagenesis ◽  
Single Amino Acid ◽  
Active Site Residues ◽  
The Core ◽  
The Difference

The correct stereochemistry of prostaglandins is a prerequisite of their biological activity and thus is under a strict enzymatic control. Recently, we cloned and characterized two cyclooxygenase (COX) isoforms in the coral Plexaura homomalla that share 97% amino acid sequence identity, yet form prostaglandins with opposite stereochemistry at carbon 15. The difference in oxygenation specificity is only partially accounted for by the single amino acid substitution in the active site (Ile or Val at position 349). For further elucidation of residues involved in the C-15 stereocontrol, a series of sequence swapping and site-directed mutagenesis experiments between 15R- and 15S-COX were performed. Our results show that the change in stereochemistry at carbon 15 of prostaglandins relates mainly to five amino acid substitutions on helices 5 and 6 of the coral COX. In COX proteins, these helices form a helix-turn-helix motif that traverses through the entire protein, contributing to the second shell of residues around the oxygenase active site; it constitutes the most highly conserved region where even slight changes result in loss of catalytic activity. The finding that this region is among the least conserved between the P. homomalla 15S- and 15R-specific COX further supports its significance in maintaining the desired prostaglandin stereochemistry at C-15. The results are particularly remarkable because, based on its strong conservation, the conserved middle of helix 5 is considered as central to the core structure of peroxidases, of which COX proteins are derivatives. Now we show that the same parts of the protein are involved in the control of oxygenation with 15R or 15S stereospecificity in the dioxygenase active site.

Sex Differences in Phonetic Processing: Speed of Identification of Alphabetical Sequences

1997 ◽  
Vol 85 (3_suppl) ◽  
pp. 1243-1251 ◽  
Author(s):  
Raymond L. Majeres
Keyword(s):  
Sex Differences ◽  
Phonological Processing ◽  
Critical Role ◽  
Matching Condition ◽  
Female College Students ◽  
Phonological Processes ◽  
The Difference ◽  
Verbal Processes ◽  
The Brain

Research on the sex difference in speed of matching strings of letters or digits has suggested that the difference is associated with the speed of the comparison and decision processes rather than with symbol recognition. In addition, the size of the difference is affected by whether the code used for the comparisons is figural or verbal. Given recent evidence on both the critical role of phonological processing in reading and sex differences in the lateralization of phonological processes in the brain, it was hypothesized that on a speeded task with high demands for phonological efficiency sex differences might be found even though no perceptual comparisons were required. In a study with 57 male and 60 female college students, the women were significantly faster in identifying alphabetical sequences and were more accurate than men. There were no significant sex differences on a perceptual matching condition. The results suggest that the verbal processes implicated in earlier work on sex differences in speed of symbol matching may be primarily due to sex differences in the efficiency of phonological processing.

Modeling mechanical alternans in the beating heart: advantages of a systems-oriented approach

1987 ◽  
Vol 253 (3) ◽  
pp. H690-H698 ◽  
Author(s):  
D. Adler ◽  
Y. Mahler
Keyword(s):  
Functional Dependence ◽  
Critical Role ◽  
Beating Heart ◽  
Discrete Method ◽  
End Diastolic Volume ◽  
A Value ◽  
The Difference ◽  
Experimental Findings ◽  
The Relationship

A model employing an original discrete method is proposed to explain mechanical alternans in the beating heart. This is compared with analysis using the difference-equation method, which has been utilized in some other areas of science and found to better represent the cardiac beat-to-beat behavior. The model shows the critical role of a slope with an exact value of 2 in the functional dependence between stroke volume (SV) and the end-diastolic volume (EDV). The implications of this model with respect to the factors causing sustained mechanical alternans (SMA) in the heart are shown. A criterion for determining whether SMA is caused by variations in EDV is described. However, this possibility is ruled out on the basis of experimental findings. It is further shown that SMA caused primarily by alterations in the contractile state leads to secondary variations in EDV. In this case the model predicts that the mean slope of SV as a function of EDV, as determined by the two alternating beats, has a value of 2 and is independent of the SV-EDV relation. This prediction concerning the relationship between SV and EDV is confirmed by available experimental data. The implications and advantages of the modeling approaches are explored.

scholarly journals Role of Lysosomes in Silica-Induced Inflammasome Activation and Inflammation in Absence of MARCO

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Rupa Biswas ◽  
Raymond F. Hamilton ◽  
Andrij Holian
Keyword(s):  
Inflammatory Response ◽  
Nlrp3 Inflammasome ◽  
Critical Role ◽  
Scavenger Receptor ◽  
Acid Sphingomyelinase ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
The Difference ◽  
Silica Treatment

MARCO is the predominant scavenger receptor for recognition and binding of silica particles by alveolar macrophages (AM). Previously, it was shown that mice null for MARCO have a greater inflammatory response to silica, but the mechanism was not described. The aim of this study was to determine the relationship between MARCO and NLRP3 inflammasome activity. Silica increased NLRP3 inflammasome activation and release of the proinflammatory cytokine, IL-1β, to a greater extent in MARCO−/−AM compared to wild type (WT) AM. Furthermore, in MARCO−/−AM there was greater cathepsin B release from phagolysosomes, Caspase-1 activation, and acid sphingomyelinase activity compared to WT AM, supporting the critical role played by lysosomal membrane permeabilization (LMP) in triggering silica-induced inflammation. The difference in sensitivity to LMP appears to be in cholesterol recycling since increasing cholesterol in AM by treatment with U18666A decreased silica-induced NLRP3 inflammasome activation, and cells lacking MARCO were less able to sequester cholesterol following silica treatment. Taken together, these results demonstrate that MARCO contributes to normal cholesterol uptake in macrophages; therefore, in the absence of MARCO, macrophages are more susceptible to a greater inflammatory response by particulates known to cause NLRP3 inflammasome activation and the effect is due to increased LMP.

Student Connections: The Critical Role of Student Affairs and Academic Support Services in Retention Efforts

2021 ◽  
pp. 152102512199150
Author(s):  
Jeff E. Hoyt
Keyword(s):  
Student Affairs ◽  
Support Services ◽  
Academic Support ◽  
Critical Role ◽  
Drop Out ◽  
Academic Support Services ◽  
College And Career ◽  
The Difference ◽  
The Impact

The connections we establish in college are transformative and redirect our lives to make lasting impacts on others around us and in the world. Student affairs and academic support services can make the difference in whether students drop out, fail academically or succeed in their college and career aspirations and realize a personal vision for their future. This research examines the impact of these connections on student retention in college when controlling for common predictors, and reminds us that retention is a campus-wide effort, with student affairs and academic support services serving critical roles. The article also discusses how a large open-admissions university utilized these services to promote student success.

The role of differential phase contrast in electron microscopy

1978 ◽  
Vol 36 (1) ◽  
pp. 176-177
Author(s):  
E.M. Waddell ◽  
J.N. Chapman ◽  
R.P. Ferrier
Keyword(s):  
Phase Contrast ◽  
Practical Method ◽  
Position Vector ◽  
Differential Phase ◽  
Pure Phase ◽  
Differential Phase Contrast ◽  
The Difference ◽  
Image Position ◽  
First Moment

Dekkers and de Lang (1977) have discussed a practical method of realising differential phase contrast in a STEM. The method involves taking the difference signal from two semi-circular detectors placed symmetrically about the optic axis and subtending the same angle (2α) at the specimen as that of the cone of illumination. Such a system, or an obvious generalisation of it, namely a quadrant detector, has the characteristic of responding to the gradient of the phase of the specimen transmittance. In this paper we shall compare the performance of this type of system with that of a first moment detector (Waddell et al.1977).For a first moment detector the response function R(k) is of the form R(k) = ck where c is a constant, k is a position vector in the detector plane and the vector nature of R(k)indicates that two signals are produced. This type of system would produce an image signal given bywhere the specimen transmittance is given by a (r) exp (iϕ (r), r is a position vector in object space, ro the position of the probe, ⊛ represents a convolution integral and it has been assumed that we have a coherent probe, with a complex disturbance of the form b(r-ro) exp (iζ (r-ro)). Thus the image signal for a pure phase object imaged in a STEM using a first moment detector is b2 ⊛ ▽ø. Note that this puts no restrictions on the magnitude of the variation of the phase function, but does assume an infinite detector.

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