scholarly journals Nanomechanics of Blood Clot and Thrombus Formation

2022 ◽  
Vol 51 (1) ◽  
Author(s):  
Marco M. Domingues ◽  
Filomena A. Carvalho ◽  
Nuno C. Santos
Keyword(s):  
Mechanical Properties ◽  
Thrombus Formation ◽  
Blood Clot ◽  
Fibrin Clot ◽  
Annual Review ◽  
Publication Date ◽  
New Methods ◽  
Fibrin Network ◽  
Protein Cell

Mechanical properties have been extensively studied in pure elastic or viscous materials; however, most biomaterials possess both physical properties in a viscoelastic component. How the biomechanics of a fibrin clot is related to its composition and the microenvironment where it is formed is not yet fully understood. This review gives an outline of the building mechanisms for blood clot mechanical properties and how they relate to clot function. The formation of a blood clot in health conditions or the formation of a dangerous thrombus go beyond the mere polymerization of fibrinogen into a fibrin network. The complex composition and localization of in vivo fibrin clots demonstrate the interplay between fibrin and/or fibrinogen and blood cells. Studying these protein–cell interactions and clot mechanical properties may represent new methods for the evaluation of cardiovascular diseases (the leading cause of death worldwide), creating new possibilities for clinical diagnosis, prognosis, and therapy. Expected final online publication date for the Annual Review of Biophysics, Volume 51 is May 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Fibrin network structure and clot mechanical properties are altered by incorporation of erythrocytes

2009 ◽  
Vol 102 (12) ◽  
pp. 1169-1175 ◽  
Author(s):  
Kathryn Gersh ◽  
Chandrasekaran Nagaswami ◽  
John Weisel
Keyword(s):  
Mechanical Properties ◽  
Network Structure ◽  
Fibrin Clot ◽  
Scanning Electron Micrographs ◽  
Fiber Network ◽  
Fibrin Network ◽  
Clot Structure ◽  
Fibrin Network Structure

SummaryAlthough many in vitro fibrin studies are performed with plasma, in vivo clots and thrombi contain erythrocytes, or red blood cells (RBCs).To determine the effects of RBCs on fibrin clot structure and mechanical properties, we compared plasma clots without RBCs to those prepared with low (2 vol%), intermediate (5-10 vol%), or high (≥20 vol%) numbers of RBCs. By confocal microscopy, we found that low RBC concentrations had little effect on clot structure. Intermediate RBC concentrations caused heterogeneity in the fiber network with pockets of densely packed fibers alongside regions with few fibers. With high levels of RBCs, fibers arranged more uniformly but loosely around the cells. Scanning electron micrographs demonstrated an uneven distribution of RBCs throughout the clot and a significant increase in fiber diameter upon RBC incorporation. While permeability was not affected by RBC addition, at 20% or higher RBCs, the ratio of viscous modulus (G′′) to elastic modulus (G′) increased significantly over that of a clot without any RBCs. RBCs triggered variability in the fibrin network structure, individual fiber characteristics, and overall clot viscoelasticity compared to the absence of cells. These results are important for understanding in vivo clots and thrombi.

In Vivo Dynamics of the Latent Reservoir for HIV-1: New Insights and Implications for Cure

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Janet D. Siliciano ◽  
Robert F. Siliciano
Keyword(s):  
Limit Of Detection ◽  
Latent Reservoir ◽  
Annual Review ◽  
Publication Date ◽  
Viral Rebound ◽  
Major Barrier ◽  
Persons Living With Hiv ◽  
Recent Developments ◽  
Hiv 1

Although antiretroviral therapy (ART) can reduce viremia to below the limit of detection and allow persons living with HIV-1 (PLWH) to lead relatively normal lives, viremia rebounds when treatment is interrupted. Rebound reflects viral persistence in a stable latent reservoir in resting CD4+ T cells. This reservoir is now recognized as the major barrier to cure and is the focus of intense international research efforts. Strategies to cure HIV-1 infection include interventions to eliminate this reservoir, to prevent viral rebound from the reservoir, or to enhance immune responses such that viral replication is effectively controlled. Here we consider recent developments in understanding the composition of the reservoir and how it can be measured in clinical studies. We also discuss exciting new insights into the in vivo dynamics of the reservoir and the reasons for its remarkable stability. Finally we discuss recent discoveries on the complex processes that govern viral rebound. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 17 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Compositional, Structural, and Kinetic Aspects of Lipid Digestion and Bioavailability: In Vitro, In Vivo, and Modeling Approaches

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Sébastien Marze
Keyword(s):  
Annual Review ◽  
Publication Date ◽  
Lipid Digestion ◽  
Modeling Approaches ◽  
Digestion Kinetics ◽  
Food Design ◽  
Structural Aspects ◽  
Development And Evolution

Lipid digestion and bioavailability are usually investigated separately, using different approaches (in vitro, modeling, in vivo). However, a few inclusive studies show that their kinetics are closely linked. Lipid bioavailability kinetics is likely involved in the development and evolution of several diseases, so lipid digestion kinetics could be involved as well and can be modulated by food design or combination. To illustrate this possibility, the compositional and structural aspects of lipid digestion kinetics, as investigated using in vitro and modeling approaches, are presented first. Then, in vivo and mixed approaches enabling the study of both kinetics are reviewed and discussed. Finally, disparate modeling approaches are introduced, and a unifying modeling scheme is proposed, opening new perspectives for understanding the role and interactions of various factors (chemical, physical, and biological) involved in lipid metabolism. Expected final online publication date for the Annual Review of Food Science and Technology, Volume 13 is March 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Factor XIIa regulates the structure of the fibrin clot independently of thrombin generation through direct interaction with fibrin

Blood ◽  
2011 ◽  
Vol 118 (14) ◽  
pp. 3942-3951 ◽  
Author(s):  
Joke Konings ◽  
José W. P. Govers-Riemslag ◽  
Helen Philippou ◽  
Nicola J. Mutch ◽  
Julian I. Borissoff ◽  
...  
Keyword(s):  
Thrombin Generation ◽  
Thrombus Formation ◽  
Coagulation Factor ◽  
Direct Interaction ◽  
Fibrin Clot ◽  
Fiber Density ◽  
Contact Pathway ◽  
Clot Structure ◽  
Fibrin Structure

Abstract Recent data indicate an important contribution of coagulation factor (F)XII to in vivo thrombus formation. Because fibrin structure plays a key role in clot stability and thrombosis, we hypothesized that FXII(a) interacts with fibrin(ogen) and thereby regulates clot structure and function. In plasma and purified system, we observed a dose-dependent increase in fibrin fiber density and decrease in turbidity, reflecting a denser structure, and a nonlinear increase in clot stiffness with FXIIa. In plasma, this increase was partly independent of thrombin generation, as shown in clots made in prothrombin-deficient plasma initiated with snake venom enzyme and in clots made from plasma deficient in FXII and prothrombin. Purified FXII and α-FXIIa, but not β-FXIIa, bound to purified fibrinogen and fibrin with nanomolar affinity. Immunostaining of human carotid artery thrombi showed that FXII colocalized with areas of dense fibrin deposition, providing evidence for the in vivo modulation of fibrin structure by FXIIa. These data demonstrate that FXIIa modulates fibrin clot structure independently of thrombin generation through direct binding of the N-terminus of FXIIa to fibrin(ogen). Modification of fibrin structure by FXIIa represents a novel physiologic role for the contact pathway that may contribute to the pathophysiology of thrombosis.

scholarly journals Dusart syndrome: a new concept of the relationship between fibrin clot architecture and fibrin clot degradability: hypofibrinolysis related to an abnormal clot structure

Blood ◽  
1993 ◽  
Vol 82 (8) ◽  
pp. 2462-2469 ◽  
Author(s):  
JP Collet ◽  
J Soria ◽  
M Mirshahi ◽  
M Hirsch ◽  
FB Dagonnet ◽  
...  
Keyword(s):  
Blood Clot ◽  
Fibrin Clot ◽  
Important Change ◽  
High Incidence ◽  
Gel Porosity ◽  
Clot Structure ◽  
The Relationship ◽  
Dose Dependent ◽  
Thrombotic Disorder

Fibrinogen Dusart is a congenital dysfibrinogenemia (A-alpha 554 Arginine-->Cysteine) associated with severe thrombotic disorder, high incidence of thrombotic embolism, and abnormal fibrin polymerization. This thrombotic disorder was attributed to an abnormal clot thrombolysis with reduced plasminogen binding to fibrin and defective plasminogen activation by tissue plasminogen activator. The purpose of this work was to assess whether clot architecture could be involved in the thromboresistance of the fibrin Dusart and the high incidence of embolism. An important change in Dusart fibrin clot structure was identified with dramatic decrease of gel porosity (Ks), fiber diameters (d), and fiber mass-length ratios (mu) derived from permeation analysis. In addition, rigidity of the Dusart clot was found to be greatly increased compared with normal fibrin. We provide evidence that both thrombolysis resistance and abnormal rigidity of the fibrin Dusart are related to this abnormal architecture, which impairs the access of fibrinolytic enzymes to the fibrin and which is responsible for a brittle clot that breaks easily, resulting in a high incidence of embolism. Indeed, when restoring a normal clot structure by adding dextran 40 (30 mg/mL) before coagulation, clot thrombolysis and clot rigidity recovered normal values. This effect was found to be dose- dependent. We conclude that clot architecture is crucial for the propensity of blood clot to be degraded and that abnormal clot structure can be highly thrombogenic in vivo. The alpha-C domains of fibrinogen are determinant in fibrin clot structure.

scholarly journals Physiologically Based Modeling of Food Digestion and Intestinal Microbiota: State of the Art and Future Challenges. An INFOGEST Review

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Steven Le Feunteun ◽  
Ahmed Al-Razaz ◽  
Matthijs Dekker ◽  
Erwin George ◽  
Beatrice Laroche ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Historical Background ◽  
Annual Review ◽  
Publication Date ◽  
Physiologically Based ◽  
The Future ◽  
Future Challenges ◽  
Full Picture ◽  
Food Digestion

This review focuses on modeling methodologies of the gastrointestinal tract during digestion that have adopted a systems-view approach and, more particularly, on physiologically based compartmental models of food digestion and host–diet–microbiota interactions. This type of modeling appears very promising for integrating the complex stream of mechanisms that must be considered and retrieving a full picture of the digestion process from mouth to colon. We may expect these approaches to become more and more accurate in the future and to serve as a useful means of understanding the physicochemical processes occurring in the gastrointestinal tract, interpreting postprandial in vivo data, making relevant predictions, and designing healthier foods. This review intends to provide a scientific and historical background of this field of research, before discussing the future challenges and potential benefits of the establishment of such a model to study and predict food digestion and absorption in humans. Expected final online publication date for the Annual Review of Food Science and Technology, Volume 12 is March 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Effects of Platelets and Erythrocytes on the Dynamic Size and Mechanical Properties of Blood Clots during Contraction

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4225-4225
Author(s):  
Valerie Tutwiler ◽  
Rustem I. Litvinov ◽  
Tatiana Lebedeva ◽  
Fazoil I. Ataullakhanov ◽  
Douglas B. Cines ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Viscoelastic Properties ◽  
Blood Clot ◽  
Final Size ◽  
Fibrin Network ◽  
Blood Clots ◽  
Platelet Concentration ◽  
Clot Contraction ◽  
Contractile Forces ◽  
Kinetics Of

Abstract Clot contraction is a final step of blood clotting and plays a key role in hemostasis and restoring blood flow past obstructive thrombi. The volume shrinkage of clots is driven by the contractile forces generated by activated platelets and propagated by the platelet-attached viscoelastic fibrin fibers throughout the entire clot. We have recently shown that blood clot contraction results in the formation of compressed. tightly packed, polyhedral erythrocytes (polyhedrocytes) and in the redistribution of platelets and fibrin to the surface of the contracted clot as a result of the complex interplay between platelets, fibrin, and erythrocytes. This study further investigates the role of these major blood cells in the dynamic mechanical (or viscoelastic) properties of the clot and the kinetics of clot contraction. Platelet and erythrocyte levels were varied through the use of partially reconstituted blood. Samples of platelet-containing plasma with or without added erythrocytes were recalcified and activated with thrombin. The viscoelastic properties and the force of contraction of the resultant clot were determined using high precision rheology. The kinetics of contraction was analyzed using a Thromboimager (HemaCore, Moscow, Russia), which allows continuous tracking and quantitative characterization of dynamic clot size by sensing changes in the light scattering of the clot over time. As predicted, the rate and degree of clot contraction depended linearly on the platelet count over a broad range (R2=0.9881). Increased platelet concentration of greater than 500 k/μl resulted in a more than 30% increase (p<0.001) in the percentage of clot contraction at 30 minutes when compared to the lowest platelet concentration (<75 k/μl). There was a significant increase in the rate and a ~15% increase (p<0.001) in the percentage of clot contraction seen in samples with 250-300k/μl, however, and no difference in samples with 125-150k/μl when compared to the lowest platelet concentration. It was observed that increasing the hematocrit level also affected the degree of contraction with a 30% decrease (p<0.001) in the percentage of contraction seen as the erythrocyte level was increased to hematocrit >40% when compared to <10% hematocrit. There was a 10-15% decrease in the percentage of contraction seen at intermediate hematocrit levels (p<0.05). In addition to decreasing the degree of contraction, changing the cellular composition also affected the rate of contraction. Increasing the concentration of either erythrocytes or platelets resulted in a relative increase in the viscous (or plastic) properties when compared to elastic (or stiffness) properties of the clot (p<0.01), showing a complex dependence of the viscoelastic behavior of the contracting clot as a result of the addition of cells. The presence of erythrocytes resulted in a 63% increase (p<0.05) in the contractile forces that were generated by the platelet-fibrin network when compared to platelets alone. We interpret these results as a profound effect of erythrocytes on the course of clot contraction and on the final size and mechanical properties of contracted blood clots. These results reveal that the concentration of cellular components critically affects the ability of the platelet-fibrin network on the outside of the clot to generate forces needed to reduce the clot size and to compact the erythrocytes, resulting in the formation of a stiff, dense hemostatic plug with low permeability. Disclosures Ataullakhanov: HemaCore LLC: Employment, Membership on an entity's Board of Directors or advisory committees.

scholarly journals What Can We Learn About QCD and Collider Physics from $\mathcal {N}=4$ Super Yang–Mills?

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Johannes M. Henn
Keyword(s):  
State Of The Art ◽  
Annual Review ◽  
Publication Date ◽  
Collider Physics ◽  
Geometrical Structures ◽  
Feynman Integrals ◽  
Yang Mills ◽  
New Methods ◽  
Feynman Graphs ◽  
Lhc Physics

Tremendous ongoing theory efforts are dedicated to developing new methods for quantum chromodynamics (QCD) calculations. Qualitative rather than incremental advances are needed to fully exploit data that are still to be collected at the LHC. The maximally supersymmetric Yang–Mills theory, 𝒩=4 super Yang–Mills (sYM), shares with QCD the gluon sector, which contains the most complicated Feynman graphs but also has many special properties and is believed to be solvable exactly. It is natural to ask what we can learn from advances in 𝒩=4 sYM for addressing difficult problems in QCD. With this in mind, I review several remarkable developments and highlights of recent results in 𝒩=4 sYM. This includes all-order results for certain scattering amplitudes, novel symmetries, surprising geometrical structures of loop integrands, novel tools for the calculation of Feynman integrals, and bootstrap methods. While several insights and tools have already been carried over to QCD and have contributed to state-of-the-art calculations for LHC physics, I argue that there is a host of further fascinating ideas waiting to be explored. Expected final online publication date for the Annual Review of Nuclear and Particle Science, Volume 71 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Oxytocin, Neural Plasticity, and Social Behavior

2021 ◽  
Vol 44 (1) ◽  
Author(s):  
Robert C. Froemke ◽  
Larry J. Young
Keyword(s):  
Social Behavior ◽  
Neural Plasticity ◽  
Neural Circuit ◽  
Social Behaviors ◽  
Neuron Activity ◽  
Annual Review ◽  
Publication Date ◽  
Social Stimuli ◽  
Circuit Function

Oxytocin regulates parturition, lactation, parental nurturing, and many other social behaviors in both sexes. The circuit mechanisms by which oxytocin modulates social behavior are receiving increasing attention. Here, we review recent studies on oxytocin modulation of neural circuit function and social behavior, largely enabled by new methods of monitoring and manipulating oxytocin or oxytocin receptor neurons in vivo. These studies indicate that oxytocin can enhance the salience of social stimuli and increase signal-to-noise ratios by modulating spiking and synaptic plasticity in the context of circuits and networks. We highlight oxytocin effects on social behavior in nontraditional organisms such as prairie voles and discuss opportunities to enhance the utility of these organisms for studying circuit-level modulation of social behaviors. We then discuss recent insights into oxytocin neuron activity during social interactions. We conclude by discussing some of the major questions and opportunities in the field ahead. Expected final online publication date for the Annual Review of Neuroscience, Volume 44 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Environmental Toxicology Assays Using Organ-on-Chip

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Patarajarin Akarapipad ◽  
Kattika Kaarj ◽  
Yan Liang ◽  
Jeong-Yeol Yoon
Keyword(s):  
Drug Toxicity ◽  
Environmental Toxicology ◽  
In Vitro Assays ◽  
Annual Review ◽  
Publication Date ◽  
Environmental Toxicants ◽  
Toxicity Screening ◽  
On Chip

Adverse effects of environmental toxicants to human health have traditionally been assayed using in vitro assays. Organ-on-chip (OOC) is a new platform that can bridge the gaps between in vitro assays (or 3D cell culture) and animal tests. Microenvironments, physical and biochemical stimuli, and adequate sensing and biosensing systems can be integrated into OOC devices to better recapitulate the in vivo tissue and organ behavior and metabolism. While OOCs have extensively been studied for drug toxicity screening, their implementation in environmental toxicology assays is minimal and has limitations. In this review, recent attempts of environmental toxicology assays using OOCs, including multiple-organs-on-chip, are summarized and compared with OOC-based drug toxicity screening. Requirements for further improvements are identified and potential solutions are suggested. Expected final online publication date for the Annual Review of Analytical Chemistry, Volume 14 is August 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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