Fast soft-tissue deformations with FEM

Soft body simulation has been a very active research area in computer animation since Baraff and Witkin's 1998 work on cloth simulation, which led Pixar to start using such techniques in all of its animated movies that followed. Many challenges in these simulations come from different roots. From a numerical point of view, deformable systems are large sparse problems that can become numerically unstable at surprising rates and may need to be modified at each time-step. From a mathematical point of view, hyperelastic models defined by continuum mechanics need to be derived, established and configured. And from the geometric side, physical interaction with the environment and self-collisions may need to be detected and introduced into the solver. It is a fact that the Computer Graphics academia primarily focuses on offline methods, both for rendering and simulation. At the same time, the advances from the industry mainly apply to real-time rendering. However, we wondered how such high-quality simulation methods would map to a real-time use case. In this thesis, we delve into the simulation system used by Pixar's Fizt2 simulator, based on the Finite Element Method, and investigate how to apply the same techniques in real-time while preserving robustness and fidelity, altogether providing the user with some interaction mechanisms. A 3D engine for simulating deformable materials has been developed following the described models, with an interactive interface that allows the definition and configuration of scenes and later interaction with the simulation

Annexin A6 and late endosomal cholesterol modulate integrin recycling and cell migration.

Annexins are a family of proteins that bind to phospholipids in a calcium-dependent manner. Earlier studies implicated annexin A6 (AnxA6) to inhibit secretion and participate in the organization of the extracellular matrix. We recently showed that elevated AnxA6 levels significantly reduced secretion of the extracellular matrix protein fibronectin (FN). Because FN is directly linked to the ability of cells to migrate, this prompted us to investigate the role of AnxA6 in cell migration. Up-regulation of AnxA6 in several cell models was associated with reduced cell migration in wound healing, individual cell tracking and three-dimensional migration/invasion assays. The reduced ability of AnxA6-expressing cells to migrate was associated with decreased cell surface expression of αVβ3 and α5β1 integrins, both FN receptors. Mechanistically, we found that elevated AnxA6 levels interfered with syntaxin-6 (Stx6)-dependent recycling of integrins to the cell surface. AnxA6 overexpression caused mislocalization and accumulation of Stx6 and integrins in recycling endosomes, whereas siRNA-mediated AnxA6 knockdown did not modify the trafficking of integrins. Given our recent findings that inhibition of cholesterol export from late endosomes (LEs) inhibits Stx6-dependent integrin recycling and that elevated AnxA6 levels cause LE cholesterol accumulation, we propose that AnxA6 and blockage of LE cholesterol transport are critical for endosomal function required for Stx6-mediated recycling of integrins in cell migration

RTP801 mediates transneuronal toxicity in culture via extracellular vesicles

Abstract Extracellular vesicles (EVs) play a crucial role in intercellular communication, participating in the paracrine trophic support or in the propagation of toxic molecules, including proteins. RTP801 is a stress‐regulated protein, whose levels are elevated during neurodegeneration and induce neuron death. However, whether RTP801 toxicity is transferred trans‐neuronally via EVs remains unknown. Hence, we overexpressed or silenced RTP801 protein in cultured cortical neurons, isolated their derived EVs (RTP801‐EVs or shRTP801‐EVs, respectively), and characterized EVs protein content by mass spectrometry (MS). RTP801‐EVs toxicity was assessed by treating cultured neurons with these EVs and quantifying apoptotic neuron death and branching. We also tested shRTP801‐EVs functionality in the pathologic in vitro model of 6‐Hydroxydopamine (6‐OHDA). Expression of RTP801 increased the number of EVs released by neurons. Moreover, RTP801 led to a distinct proteomic signature of neuron‐derived EVs, containing more pro‐apoptotic markers. Hence, we observed that RTP801‐induced toxicity was transferred to neurons via EVs, activating apoptosis and impairing neuron morphology complexity. In contrast, shRTP801‐EVs were able to increase the arborization in recipient neurons. The 6‐OHDA neurotoxin elevated levels of RTP801 in EVs, and 6‐OHDA‐derived EVs lost the mTOR/Akt signalling activation via Akt and RPS6 downstream effectors. Interestingly, EVs derived from neurons where RTP801 was silenced prior to exposing them to 6‐OHDA maintained Akt and RPS6 transactivation in recipient neurons. Taken together, these results suggest that RTP801‐induced toxicity is transferred via EVs, and therefore, it could contribute to the progression of neurodegenerative diseases, in which RTP801 is involved

Stress and coping strategies of families of pediatric solid organ transplant recipients in times of pandemic

Pediatric solid organ transplantation (SOT) is a chronic condition that impacts the whole family system. The objective of this study is to evaluate psychopathology, family stress, and coping strategies in families of SOT recipients compared to families of healthy children and adolescents. Moreover, it analyzes if the stress related to the COVID-19 pandemic has had an additional impact on these families. The sample was recruited between May and July 2021, during the fourth and fifth wave of the pandemic in Spain. It consisted of 102 families, 51 with a pediatric recipient who had undergone a SOT (liver, kidney, heart, or lung) and 51 healthy controls, matched by child age and gender. A primary caregiver from each family answered an online sociodemographic questionnaire and different tests to evaluate family stress, depression, anxiety, coping strategies, and effects of the pandemic on the family. Caregivers were mostly mothers (89.2%). Families of SOT recipients showed greater anxiety (U = 863.5, p = 0.003) and more total stress, stress related to childcare (t = −2.043; p = 0.045), and parent-child interaction stress (U = 355.5, p = 0.015). SOT families used more avoidance strategies, specifically denial (U = 889.5; p = 0.010) and abandonment of coping efforts (U = 1,013; p = 0.047), more religious strategies (U = 792.5; p = 0.031), and fewer social support coping strategies (t = 2.098; p = 0.038). No differences were found between groups in terms of exposure, impact, and distress more than 1 year after the start of the pandemic. SOT families showed clinical levels of anxiety, more parent-child interaction stress, more difficulties in taking care of their child, more avoidance and religious strategies, and less use of social support strategies, even 4 years after transplantation. The pandemic did not have an additional differential effect on SOT families. Caregivers of SOT patients can benefit from psychological interventions focused on parents' mental health, parent-child connectedness, skill building, and social support aid groups, with attention to multiculturalism and promoting a better balance between caregivers. There is a need for family interventions that are maintained over time. Strategies that offer this support to families through digital resources can facilitate adjustment to chronic illness, especially in pandemic times

Annexin A6 and late endosomal cholesterol modulate integrin recycling and cell migration.

Annexins are a family of proteins that bind to phospholipids in a calcium-dependent manner. Earlier studies implicated annexin A6 (AnxA6) to inhibit secretion and participate in the organization of the extracellular matrix. We recently showed that elevated AnxA6 levels significantly reduced secretion of the extracellular matrix protein fibronectin (FN). Because FN is directly linked to the ability of cells to migrate, this prompted us to investigate the role of AnxA6 in cell migration. Up-regulation of AnxA6 in several cell models was associated with reduced cell migration in wound healing, individual cell tracking and three-dimensional migration/invasion assays. The reduced ability of AnxA6-expressing cells to migrate was associated with decreased cell surface expression of αVβ3 and α5β1 integrins, both FN receptors. Mechanistically, we found that elevated AnxA6 levels interfered with syntaxin-6 (Stx6)-dependent recycling of integrins to the cell surface. AnxA6 overexpression caused mislocalization and accumulation of Stx6 and integrins in recycling endosomes, whereas siRNA-mediated AnxA6 knockdown did not modify the trafficking of integrins. Given our recent findings that inhibition of cholesterol export from late endosomes (LEs) inhibits Stx6-dependent integrin recycling and that elevated AnxA6 levels cause LE cholesterol accumulation, we propose that AnxA6 and blockage of LE cholesterol transport are critical for endosomal function required for Stx6-mediated recycling of integrins in cell migration

Cholesterol regulates Syntaxin 6 trafficking at the TGN-endosomal boundaries

Inhibition of cholesterol export from late endosomes causes cellular cholesterol imbalance, including cholesterol depletion in the trans-Golgi network (TGN). Here, using Chinese hamster ovary (CHO) Niemann-Pick type C1 (NPC1) mutant cell lines and human NPC1 mutant fibroblasts, we show that altered cholesterol levels at the TGN/endosome boundaries trigger Syntaxin 6 (Stx6) accumulation into VAMP3, transferrin, and Rab11-positive recycling endosomes (REs). This increases Stx6/VAMP3 interaction and interferes with the recycling of αVβ3 and α5β1 integrins and cell migration, possibly in a Stx6-dependent manner. In NPC1 mutant cells, restoration of cholesterol levels in the TGN, but not inhibition of VAMP3, restores the steady-state localization of Stx6 in the TGN. Furthermore, elevation of RE cholesterol is associated with increased amounts of Stx6 in RE. Hence, the fine-tuning of cholesterol levels at the TGN-RE boundaries together with a subset of cholesterol-sensitive SNARE proteins may play a regulatory role in cell migration and invasion