Rupture In Response Research Articles

Gender dimorphic ACL strain in response to combined dynamic 3D knee joint loading: Implications for ACL injury risk

While gender-based differences in knee joint anatomies/laxities are well documented, the potential for them to precipitate gender-dimorphic ACL loading and resultant injury risk has not been considered. To this end, we generated gender-specific models of ACL strain as a function of any six degrees of freedom (6DOF) knee joint load state via a combined cadaveric and analytical approach. Continuously varying joint forces and torques were applied to five male and five female cadaveric specimens and recorded along with synchronous knee flexion and ACL strain data. All data (~ 10,000 samples) were submitted to specimen-specific regression analyses, affording ACL strain predictions as a function of the combined 6 DOF knee loads. Following individual model verifications, generalized gender-specific models were generated and subjected to 6 DOF external load scenarios consistent with both a clinical examination and a dynamic sports maneuver. The ensuing model-based strain predictions were subsequently examined for gender-based discrepancies. Male and female specimen-specific models predicted ACL strain within 0.51% ± 0.10% and 0.52% ± 0.07% of the measured data respectively, and explained more than 75% of the associated variance in each case. Predicted female ACL strains were also significantly larger than respective male values for both simulated 6 DOF load scenarios. Outcomes suggest that the female ACL will rupture in response to comparatively smaller external load applications. Future work must address the underlying anatomical/laxity contributions to knee joint mechanical and resultant ACL loading, ultimately affording prevention strategies that may cater to individual joint vulnerabilities.

The GA-signaling repressor RGL3 represses testa rupture in response to changes in GA and ABA levels

We recently reported that the DELLA factor RGL2 represses testa rupture in response to changes in ABA and GA levels. Here, we provide genetic evidence that this observation extends to RGL3, another DELLA factor whose function was not previously characterized. However, RGL3’s repressive activity was seen only in an rgl2 genetic background. This may be explained by the observation that RGL3’s mRNA levels are positively regulated by ABA and low GA but to a lesser extent than those of RGL2. This could ensure that RGL2’s repressive activity dominates relative to that of RGL3 under most germination conditions.

The Molecular and Cellular Basis of Atherosclerosis and Plaque Rupture

Atherosclerosis complicated by plaque rupture or disruption and thrombosis is primarily responsible for the development of acute coronary syndromes. Plaques with a large extracellular lipid-rich core, thin fibrous cap due to reduced collagen content and smooth muscle density, and increased numbers of activated macrophages and mast cells, appear to be vulnerable to rupture. Plaque disruption tends to occur at points at which the plaque surface is weakest and most vulnerable, which coincide with points at which stresses, resulting from biomechanical and hemodynamic forces acting on plaques, are concentrated. Reduced matrix synthesis as well as increased matrix degradation predisposes vulnerable plaques to rupture in response to extrinsic mechanical or hemodynamic stresses. Modification of endothelial dysfunction and reduction of vulnerability to plaque rupture and thrombosis may lead to plaque stabilization. The broad concept of plaque stabilization, although attractive, has not yet been rigorously validated in humans. This article reviews the mechanism of atherosclerosis development and the pathophysiology of acute coronary syndromes in order to provide a molecular and cellular basis for understanding how plaque passivation might be accomplished in clinical medicine.

Clinical Implications and Mechanisms of Plaque Rupture in the Acute Coronary Syndromes

Coronary atherosclerosis complicated by plaque rupture or disruption and thrombosis is primarily responsible for the development of acute coronary syndromes. Plaques with a large extracellular lipid-rich core, a thin fibrous cap due to reduced collagen content and smooth muscle density, and increased numbers of activated macrophages and mast cells appear to be vulnerable to rupture. Plaque disruption tends to occur at points at which the plaque surface is weakest and most vulnerable, which coincide with points at which stresses resulting from biomechanical and hemodynamic forces acting on plaques are concentrated. Reduced matrix synthesis as well as increased matrix degradation predisposes vulnerable plaques to rupture in response to extrinsic mechanical or hemodynamic stresses. Modification of endothelial dysfunction and reduction of vulnerability to plaque rupture and thrombosis may lead to plaque stabilization. These concepts have significant clinical implications that are just beginning to be explored and incorporated into clinical practice. This article reviews the mechanism of coronary atherosclerosis development and the pathophysiology of acute coronary syndromes to provide a framework for understanding how plaque passivation might be accomplished in clinical medicine.

Multiple Signaling Defects in the Absence of RIP140 Impair Both Cumulus Expansion and Follicle Rupture

The nuclear receptor corepressor RIP140 is essential in the ovary for ovulation, but is not required for follicle growth and luteinization. To identify genes that may be subject to regulation by RIP140 or play a role in ovulation, we compared ovarian gene expression profiles in untreated immature wild-type and RIP140 null mice and after treatment with pregnant mare serum gonadotropin and human chorionic gonadotropin. Many genes involved in signaling, extracellular matrix formation, cell-cell attachment, and adhesion were aberrantly regulated in the absence of RIP140, varying according to the hormone status of the mice. Notable among these was the reduced expression of a number of genes that encode components of signaling pathways and matrix proteins required for cumulus expansion, a key remodeling process necessary for ovulation. Histological analysis confirmed that cumulus expansion in RIP140 null mice is reduced, oocyte detachment from the mural cell wall is impaired, and follicles fail to rupture in response to LH. Although the expression of many genes involved in cumulus cell expansion was reduced, there was a subset of genes involved in extracellular matrix formation and cell-cell interactions that was up-regulated and may interfere with ovarian tissue remodeling. We propose that widespread gene dysregulation in ovarian tissues in the absence of RIP140 leads to the anovulatory phenotype. This helps to define an important role for RIP140 in the regulation of multiple processes leading to ovulation.

Disintegration of planar liquid film impacted by two-dimensional gas jets

The distortion and break-up of a thin planar liquid film impacted by two gas jets while discharging from a twin-fluid atomizer is studied numerically. The gas momentum vector has components normal and parallel to the liquid stream. Viscosity and compressibility are neglected in both the liquid phase and the gas phase. The reduced-dimension (lubrication) approximation is employed to describe the nonlinear distortion and breakup of the thin film. The gas-phase dynamics are modelled by using a boundary-element-method formulation. For the considered parameter range and for a given energy expenditure, direct modulation of liquid-phase velocities at the nozzle exit is found to be more effective in causing film rupture than indirect modulation via adjacent impacting gas jets. In the former case, dilational film modulation results in shorter breakup lengths than sinuous modulation. On the other hand, for gas-jet modulated films, sinuous mode forcing is more effective than dilational forcing for the same energy input. Co-flowing gas streams significantly alter wavelengths and amplitudes of film disturbances generated by direct film modulation. Large ratios of gas-jet momentum to liquid-film momentum result in “immediate” film rupture in response to the dynamics of the impacting gas jets, whereas for lower ratios films disintegration occurs further downstream after continuous growth of the initial disturbances. Film distortion is characterized by the formation of fluid blobs or long band-like films depending on Weber number values and density ratio.