Biology subjects

Liu, M.

Publications and source records attributed to Liu, M..

At least 505 records · Page 28Linked to original sources

bioRxiv2019

Multilayered N-glycoproteomics reveals impaired N-glycosylation promoting Alzheimer’s disease

Alzheimers disease (AD) is one of the most common neurodegenerative diseases that currently lacks clear pathogenesis and effective treatment. Protein glycosylation is ubiquitous in brain tissue and site-specific analysis of N-glycoproteome, which is technically challenging, can advance our understanding of the glycoproteins role in AD. In this study, we profiled the multilayered variations in proteins, N-glycosites, N-glycans, and in particular site-specific N-glycopeptides in the APP/PS1 and wild type mouse brain through combining pGlyco 2.0 strategy with other quantitative N-glycoproteomic strategies. The comprehensive brain N-glycoproteome landscape was constructed, and rich details of the heterogeneous site-specific protein N-glycosylations were exhibited. Quantitative analyses explored generally downregulated N-glycosylation involving proteins such as glutamate receptors, as well as fucosylated and oligo-mannose type glycans in APP/PS1 mice versus wild type mice. Moreover, our preliminary functional study revealed that N-glycosylation was crucial for the membrane localization of NCAM1 and for maintaining the excitability and viability of neuron cells. Our work offered a panoramic view of the N-glycoproteomes in Alzheimers disease and revealed that generally impaired N-glycosylation promotes Alzheimers disease progression.

systems biology↗

bioRxiv2019

3D Multicolor Nanoscopy at 10,000 Cells a Day

Diffraction-unlimited single-molecule techniques like STORM and (F)PALM enable three-dimensional (3D) fluorescence imaging at tens of nanometer resolution and are invaluable to investigate sub-cellular organization. The multitude of camera frames required to reconstruct a super-resolved image limits the typical throughput of these techniques to tens of cells per day, rendering these methods incompatible with large-scale cell biological or clinical application. STORM acquisition rates can be increased by over an order of magnitude, however the data volumes of about 40 TB a day and concomitant analysis burdens exceed the capacity of existing workflows. Here we present an integrated platform which transforms SMLM from a trick-pony technique into a work horse for cell biology. We leverage our developments in microscopy-specific data compression, distributed storage, and distributed analysis to automatically perform real-time localization analysis, which enable SMLM at throughputs of 10,000 cells a day. We implemented these advances in a fully-integrated environment that supports a highly-flexible architecture for distributed analysis, enabling quickly- and graphically-reconfigurable analyses to be automatically initiated from the microscope during acquisition, remotely executed, and even feedback and queue new acquisition tasks on the microscope. We demonstrate the utility of this framework by imaging hundreds of cells per well in multi-well sample formats. Our platform, the PYthon-Microscopy Environment (PYME), is easily configurable for hardware control on custom microscopes, and includes a plugin framework so users can readily extend all components of their imaging, visualization, and analysis pipeline. PYME is cross-platform, open source, and efficiently puts high-caliber visualization and analysis tools into the hands of both microscope developers and users.

biophysics↗

bioRxiv2019

Fragment-based screening identifies molecules targeting the substrate-binding ankyrin repeat domains of tankyrase

The PARP enzyme and scaffolding protein tankyrase (TNKS, TNKS2) uses its ankyrin repeat clusters (ARCs) to bind a wide range of proteins and thereby controls diverse cellular functions. A number of these are implicated in cancer-relevant processes, including Wnt/{beta}-catenin signaling and telomere maintenance. The ARCs recognise a conserved tankyrase-binding peptide motif (TBM). All currently available tankyrase inhibitors target the catalytic domain and inhibit tankyrases poly(ADP-ribosyl)ation function. However, there is emerging evidence that catalysis-independent \"scaffolding\" mechanisms contribute to tankyrase function. Here we report a fragment-based screening program against tankyrase ARC domains, using a combination of biophysical assays, including differential scanning fluorimetry (DSF) and nuclear magnetic resonance (NMR). We identify fragment molecules that will serve as starting points for the development of tankyrase substrate binding antagonists. Such compounds will enable probing the scaffolding functions of tankyrase, and may, in the future, provide potential alternative therapeutic approaches to inhibiting tankyrase activity in cancer and other conditions.

biophysics↗

bioRxiv2019

Exploring the influence of surface proteins on probiotic activity of Lactobacillus pentosus HC-2 in Litopenaeus vannamei midgut via Label-free quantitative proteomic analysis

Our previously work showed that Lactobacillus pentosus HC-2 as probiotic could improve the growth performance, immune response, gut bacteria diversity and disease resistance of Litopenaeus vannamei. However, the probiotic mechanism of was not fully characterized. In the present study, histology and proteomic analysis was performed to explore the influence of HC-2 surface protein on its probiotic effects to L. vannamei after feeding the intact surface proteins or the probiotic treated with lithium chloride (LiCl) to remove non-covalently bound surface proteins or no probiotic for four weeks. Histological observation found that feeding with normal HC-2 obviously improved the intestinal histology and enhanced the protective effect against pathogens damages, but fed with LiCl-treated HC-2 didnt improve the intestinal environment. A total over 2,764 Peptides and 1,118 uniproteins were identified from L. vannamei midgut, 211 proteins were significant differentially expressed normal HC-2 group compared with control, 510 proteins were significant differentially expressed in LiCl-tread HC-2 group compared with control, and 458 proteins were significant differentially expressed in LiCl-tread HC-2 group compared with normal HC-2 group. GO/KEGG enrichment analysis of the significantly different proteins demonstrated that fed with normal HC-2 mainly induced immune response, metabolic, cell adhesion and cell-cell signaling related proteins up-regulation, which were contributed to bacteria adhesion and colonization in midgut to improve shrimp immune system and growth, but these proteins were suppressed after feeding with deprived surface proteins bacteria. Taken together, these results indicating that the surface proteins were indispensable for HC-2 to execute probiotic effects in midgut of shrimp.

microbiology↗

bioRxiv2019

Requirement for TRanslocon-Associated Protein (TRAP) α in insulin biogenesis

The mechanistic basis for the biogenesis of peptide hormones and growth factors is poorly understood. Here we show that the conserved endoplasmic reticulum (ER) membrane translocon-associated protein (TRAP) , also known as signal sequence receptor 1 (SSR1)1, plays a critical role in the biosynthesis of insulin. A genetic screen in the nematode Caenorhabditis elegans revealed trap-1, which encodes the C. elegans TRAP ortholog, as a modifier of DAF-2 insulin receptor (InsR) signaling. Genetic analysis indicates that TRAP-1 acts upstream of DAF-2/InsR to control C. elegans development. Endogenous C. elegans TRAP-1 and mammalian TRAP both localized to the ER. In pancreatic beta cells, TRAP deletion impaired preproinsulin translocation but did not affect the synthesis of 1-antitrypsin, indicating that TRAP selectively influences the translocation of a subset of secreted proteins. Surprisingly, loss of TRAP function also resulted in disruption of distal steps in insulin biogenesis including proinsulin processing and secretion. These results show that TRAP assists in the ER translocation of preproinsulin and unveil unanticipated additional consequences of TRAP loss-of-function on the intracellular trafficking and maturation of proinsulin. The association of common intronic single nucleotide variants in the human TRAP gene with susceptibility to Type 2 diabetes and pancreatic beta cell dysfunction2 suggests that impairment of preproinsulin translocation and proinsulin trafficking may contribute to the pathogenesis of Type 2 diabetes.

genetics↗

bioRxiv2019

CTCF-mediated Chromatin Structures Dictate the Spatio-temporal Propagation of Replication Foci

Mammalian DNA replication is initiated at numerous replication origins, which are clustered into thousands of replication domains (RDs) across the genome. However, it remains unclear whether the replication origins within each RD are activated stochastically. To understand how replication is regulated at the sub-RD level, we directly visualized the spatio-temporal organization, morphology, and in situ epigenetic signatures of individual replication foci (RFi) across S-phase using super-resolution stochastic optical reconstruction microscopy (STORM). Importantly, we revealed a hierarchical radial pattern of RFi propagation that reverses its directionality from early to late S-phase, and is diminished upon caffeine treatment or CTCF knockdown. Together with simulation and bioinformatic analyses, our findings point to a CTCF-organized REplication Propagation (CoREP) model. The CoREP model suggests a non-random selection mechanism for replication activation mediated by CTCF at the sub-RD level, as well as the critical involvement of local chromatin environment in regulating replication in space and time.

cell biology↗

bioRxiv2019

Gene Panel Sequencing in a Chinese High-risk Breast Cancer Cohort

Currently, over 20 genes have been defined that can confer susceptibility for high-risk breast cancer. Although research has proved the utility of multiple-gene sequencing in the assessment of breast cancer risk, there is little data from China patients. Here, we use a multiple-gene sequencing panel to identify the variant spectrum in Chinese high-risk breast cancer subjects.\n\nA total of 829 Chinese high-risk breast cancer patients participated in the research. The coding regions of 115 hereditary cancer susceptibility genes were sequenced using a next generation sequencing platform. In total, 193 pathogenic variants were identified in 45 genes from 177 patients. The pathogenic variant carrier rate is 21.4%: with 10.5% patients carrying a BRCA1 or BRCA2 mutation only, 10.0% of patients carried non-BRCA gene mutations only, while 1.0% of patients carried both a BRCA1/2 and a non-BRCA gene mutation. Variants of uncertain significance (VUS) totaling 2632 were identified in 115 genes from 787 of 829 patients: 82.5% patients carried more than one VUS, and only 5.1% patients did not carry any VUS. Families carrying pathogenic variants were tracked and adenoma was founded in three of them. Our data provide a comprehensive analysis of potential susceptibility variations of high-risk for breast cancer in a Chinese population. This data will be useful for the comparison of the susceptibility variation spectrum between different populations and to discover potential pathogenic variants to improve the prevention and treatment of high-risk breast cancer.

cancer biology↗

bioRxiv2018

Cysteine dioxygenase 1 is a metabolic liability for non-small cell lung cancer

NRF2 is emerging as a major regulator of cellular metabolism. However, most studies have been performed in cancer cells, where co-occurring mutations and tumor selective pressures complicate the influence of NRF2 on metabolism. Here we use genetically engineered, non-transformed primary cells to isolate the most immediate effects of NRF2 on cellular metabolism. We find that NRF2 promotes the accumulation of intracellular cysteine and engages the cysteine homeostatic control mechanism mediated by cysteine dioxygenase 1 (CDO1), which catalyzes the irreversible metabolism of cysteine to cysteine sulfinic acid (CSA). Notably, CDO1 is preferentially silenced by promoter methylation in non-small cell lung cancers (NSCLC) harboring mutations in KEAP1, the negative regulator of NRF2. CDO1 silencing promotes proliferation of NSCLC by limiting the futile metabolism of cysteine to the wasteful and toxic byproducts CSA and sulfite, and depletion of cellular NADPH. Thus, CDO1 is a metabolic liability for NSCLC cells with high intracellular cysteine, particularly NRF2/KEAP1 mutant cells.

cancer biology↗

bioRxiv2018

Biological adaptation under fluctuating selection

Bet-hedging--an evolutionary strategy that reduces fitness variance at the expense of lower mean fitness--is the primary explanation for most forms of biological adaptation to environmental unpredictability. However, most applications of bet-hedging theory to biological problems have largely made unrealistic demographic assumptions, such as non-overlapping generations and fixed population sizes. Consequently, the generality and applicability of bet-hedging theory to real world phenomena remains unclear. Here we use continuous-time, stochastic Lotka-Volterra models to relax overly restrictive demographic assumptions and explore a suite of biological adaptations to fluctuating environments. We discover a novel \"rising-tide strategy\" that--unlike the bet-hedging strategy--generates both a higher mean and variance in fitness. The positive fitness effects of the rising-tide strategys specialization to good years can overcome any negative effects of higher fitness variance in unpredictable environments. Moreover, we show not only that the rising-tide strategy will be selected for over a much broader range of environmental conditions than the bet-hedging strategy, but also under more realistic demographic circumstances. Ultimately, our model demonstrates that there are likely to be a wide range of ways that organisms respond to environmental unpredictability.

ecology↗

bioRxiv2018

Differential gene expression, including Sjfs800, in Schistosoma japonicum females before, during, and after male-female pairing

Schistosomiasis is a prevalent but neglected tropical disease caused by parasitic trematodes of the genus Schistosoma, with the primary disease-causing species being S. haematobium, S. mansoni, and S. japonicum. Male-female pairing of schistosomes is necessary for sexual maturity and the production of a large number of eggs, which are primarily responsible for schistosomiasis dissemination and pathology. Here, we used microarray hybridization, bioinformatics, quantitative PCR, in situ hybridization, and gene silencing assays to identify genes that play critical roles in S. japonicum reproduction biology, particularly in vitellarium development, a process that affects male-female pairing, sexual maturation, and subsequent egg production. Microarray hybridization analyses generated a comprehensive set of genes differentially transcribed before and after male-female pairing. Although the transcript profiles of females were similar 16 and 18 days after host infection, marked gene expression changes were observed at 24 days. The 30 most abundantly transcribed genes on day 24 included those associated with vitellarium development. Among these, genes for female-specific 800 (fs800), eggshell precursor protein, and superoxide dismutase (cu-zn-SOD) were substantially upregulated. Our in situ hybridization results in female S. japonicum indicated that cu-zn-SOD mRNA was highest in the ovary and vitellarium, eggshell precursor protein mRNA was expressed in the ovary, ootype, and vitellarium, and Sjfs800 mRNA was observed only in the vitellarium, localized in mature vitelline cells. Knocking down the Sjfs800 gene in female S. japonicum by approximately 60% reduced the number of mature vitelline cells, decreased rates of pairing and oviposition, and decreased the number of eggs produced in each male-female pairing by about 50%. These results indicate that Sjfs800 is essential for vitellarium development and egg production in S. japonicum and suggest that Sjfs800 regulation may provide a novel approach for the prevention or treatment of schistosomiasis.\n\nAuthor SummarySchistosomiasis is a common but largely unstudied tropical disease caused by parasitic trematodes of the genus Schistosoma. The eggs of schistosomes are responsible for schistosomiasis transmission and pathology, and the production of these eggs is dependent on the pairing of females and males. In this study, we determined which genes in Schistosoma japonicum females were differentially expressed before and after pairing with males, identifying the 30 most abundantly expressed of these genes. Among these 30 genes, we further characterized those in female S. japonicum that were upregulated after pairing and that were related to reproduction and vitellarium development, a process that affects male-female pairing, sexual maturation, and subsequent egg production. We identified three such genes, S. japonicum female-specific 800 (Sjfs800), eggshell precursor protein, and superoxide dismutase, and confirmed that the mRNAs for these genes were primarily localized in reproductive structures. By using gene silencing techniques to reduce the amount of Sjfs800 mRNA in females by about 60%, we determined that Sjfs800 plays a key role in development of the vitellarium and egg production. This finding suggests that regulation of Sjfs800 may provide a novel approach to reduce egg counts and thus aid in the prevention or treatment of schistosomiasis.

genomics↗

bioRxiv2018

Emotional Mirrors in the Rat’s Anterior Cingulate Cortex

AbstractHow do the emotions of others affect us? The human anterior cingulate cortex (ACC) responds while experiencing pain in the self and witnessing pain in others, but underlying cellular mechanisms remain poorly understood. Here we show the ACC (area 24) contains neurons responding when a rat experiences pain and while witnessing another receive footshocks. Most of these do not respond to a fear conditioned tone (CS). Deactivating this region reduces freezing while witnessing footshocks to others but not while hearing the CS. A decoder trained on spike counts while witnessing footshocks can decode the animals own pain intensity when experiencing pain. Mirror-like neurons thus exist in ACC that encode the pain of others in a code shared with pain but not fear in the self.\n\nOne Sentence SummaryACC contains neurons responding selectively when a rat witnesses anothers pain and experiences pain in the self.

neuroscience↗

bioRxiv2018

B1a cells protect against Schistosoma japonicum-induced liver inflammation and fibrosis by controlling monocyte infiltration

During Schistosoma infection, lack of B cells results in more severe granulomas, inflammation, and fibrosis in the liver, but the mechanisms underlying this pathology remain unclear. Thus, our aim was to clarify the mechanisms underpinning the immunomodulation of B cells in mice infected with Schistosoma japonicum. We found that B cell deficiency led to aggravated liver pathology, as demonstrated by increases in the size of the egg-associated granulomas, alanine transaminase levels, and collagen deposition. Compared with infected wild-type mice, infected B cell-deficient MT mice showed increased infiltration of Ly6Chi monocytes and higher levels of proinflammatory cytokines (tumor necrosis factor alpha, interleukin 6, and interleukin 12) and chemokines ([C-C motif] ligands (CCL)2, CCL3, CCL4, and CCL5). The results of flow cytometric analysis and cell transfer experiments showed that B1a cells increased significantly in the liver following S. japonicum infection, with some of those cells deriving from the peritoneal cavity. We also found that secretion of IL-10 from hepatic B cells increased significantly in infected wild-type mice and that this IL-10 was mainly derived from B1a cells. In addition, adoptively transferring peritoneal cavity B cells purified from wild-type, but not from IL-10-deficient mice, to MT mice significantly reduced liver pathology and liver infiltration of Ly6Chi monocytes. These reductions were accompanied by decreases in the expression levels of chemokines and inflammatory cytokines. Taken together, these data indicated that after S. japonicum infection, an increased number of hepatic B1a cells secrete IL-10, which inhibits the expression of chemokines and cytokines and suppresses the infiltration of Ly6Chi monocytes into the liver thereby alleviating liver early inflammation and late fibrosis. Understanding this immunomodulatory role of B1a cells in schistosomiasis may lead to the development of therapeutic strategies for Schistosoma-induced liver disease.\n\nAuthor summaryInfection with Schistosoma, a waterborne parasitic flatworm (trematode) commonly called a blood fluke, results in strong granulomatous inflammation caused by the deposition of eggs in the liver. A granuloma is a substantial immune cell infiltration around the eggs intermixed with liver cells that can protect the host against liver damage. However, excessive infiltration and inflammation can lead to severe liver injury and fibrosis. Here, we found that B1a cells accumulate in the liver of mice after S. japonicum-induced infection and that these B1a cells release the anti-inflammatory cytokine interleukin 10 to regulate inflammation. The B1a cell-derived interleukin 10 inhibits the expression of chemokines (which attract cells such as monocytes to sites of infection or inflammation) and thus restrains excessive infiltration of Ly6Chi monocytes (which may have proinflammatory activity) into the liver, thereby alleviating early inflammation and later fibrosis. Our study provides insight into the immunomodulation of B1a cells in schistosomiasis and offers key information for the development of therapeutic strategies in Schistosoma-induced liver disease.

immunology↗

bioRxiv2018

Influenza incidence prediction for the United States: an update for the 2018-2019 season

IntroductionSeasonal influenza causes a high disease burden every year in the United States and worldwide. Anticipating epidemic size ahead of season can contribute to preparedness and more targetted control and prevention of seasonal influenza.\n\nMethodsA recently developed process-based epidemiological model that incorporates evolutionary change of the virus and generates incidence forecasts for the H3N2 subtype ahead of the season, was previously validated by several statistical criteria, including an accurate real-time prediction for the 2016-2017 influenza season. With this model, a new forecast is generated here for the upcoming 2018-2019 season. The accuracy of predictions published for the 2017-2018 season is also retrospectively evaluated.\n\nResultsFor 2017-2018, the model correctly predicted the dominance of the H3N2 subtype and its higher than average incidence. Based on surveillance and sequence data up to June 2018, the new forecast for the upcoming 2018-2019 season indicates low levels for H3N2, and suggests an H1N1 dominant season with low incidence of influenza B.\n\nDiscussionReal-time forecasts, those generated with a model that was parameterized based on data preceding the predicted season, allows valuable evaluation of the approach. Anticipating the dominant subtype and the size of the upcoming epidemic ahead of season informs disease control. Further studies are needed to promote more accurate ahead-of-season forecasts and extend the approach to multiple subtypes.

bioinformatics↗

bioRxiv2018

Sequencing of the MHC region defines HLA-DQA1 as the major independent risk for anti-citrullinated protein antibodies (ACPA)-positive rheumatoid arthritis in Han population

The strong genetic contribution of the major histocompatibility complex (MHC) to rheumatoid arthritis (RA) susceptibility has been generally attributed to HLA-DRB1. However, due to the high linkage disequilibrium in the MHC region, it is difficult to define the real or/and additional independent genetic risks using the conventional HLA genotyping or chip-based microarray technology. By the capture sequencing of entire MHC region for discovery and HLA-typing for validation in 2,773 subjects of Han ancestry, we identified HLA-DQ1:160D as the strongest independent genetic risk for anti-citrullinated protein antibodies (ACPA)-positive RA in Han population (P = 6.16 x 10-36, OR=2.29). Further stepwise conditional analysis revealed that DR{beta}1:37N has an independent protective effect on ACPA-positive RA (P = 5.81 x 10-16, OR=0.49). The DQ1:160 coding allele DQA1*0303 displayed high impact on joint radiographic severity, especially in patients with early disease and smoking (P = 3.02 x 10-5). Interaction analysis by comparative molecular modeling revealed that the negative charge of DQ1:160D stabilizes the dimer of dimers, leading to an increased T cell activation. The electrostatic potential surface analysis indicated that the negative charged DR{beta}1:37N encoding alleles could bind with epitope P9 arginine, thus may result in a decreased RA susceptibility.\n\nIn this study, we provide the first evidence that HLA-DQA1, instead of HLA-DRB1, is the strongest and independent genetic risk for ACPA-positive RA in Chinese Han population. Our study also illustrates the value of MHC deep sequencing for fine mapping disease risk variants in the MHC region.

genetics↗

bioRxiv2018

A Chemically-triggered Transition from Conflict to Cooperation in Burying Beetles

Although interspecific competition has long been recognized as a major driver of trait divergence and adaptive evolution1-3, relatively little effort has focused on how it influences the evolution of intraspecific cooperation4-6. Here we identify the mechanism by which the perceived pressure of interspecific competition influences the transition from intraspecific conflict to cooperation in a facultative cooperatively breeding species, the Asian burying beetle Nicrophorus nepalensis. In their natural environment in central Taiwan, N. nepalensis are typically aggressive to conspecifics and only cooperate with others of their own species at critical carcass resources in the presence of blowflies, their primary competitors7. We demonstrate that beetles form larger groups and are more cooperative in carcass preparation in warmer environments where the pressure of interspecific competition with blowflies is highest8. To test the hypothesis that the presence of blowflies promotes beetle cooperation and to identify the mechanism by which this occurs, we manipulated blowfly larvae on carcasses in the lab. We not only found that beetles are more cooperative at carcasses when blowfly maggots have begun to digest the tissue, but that this social cooperation appears to be triggered by a single chemical cue-- dimethyl disulfide (DMDS)--emitted from carcasses consumed by blowflies but not from control carcasses lacking blowflies. Our results provide experimental evidence that interspecific competition promotes the transition from intraspecific conflict to cooperation in N. nepalensis via a surprisingly simple social chemical cue that is a reliable indicator of interspecific competition. This finding helps bridge the gap between the proximate and ultimate factors regulating the transition between cooperation and conflict and moves toward a more comprehensive understanding of the evolution of mechanisms governing intraspecific variation in social behaviour.

evolutionary biology↗

bioRxiv2018

Coordinative Metabolism of Glutamine Carbon and Nitrogen in proliferating Cancer Cells Under Hypoxia

Under hypoxia, most of glucose is converted to secretory lactate, which leads to the lack of carbon source from glucose and thus the overuse of glutamine-carbon. However, under such a condition how glutamine nitrogen is disposed to avoid releasing potentially toxic ammonia remains to be determined. Here we identify a metabolic flux of glutamine to secretory dihydroorotate under hypoxia. We found that glutamine nitrogen is indispensable to nucleotide biosynthesis, but enriched in dihyroorotate and orotate rather than processing to its downstream uridine monophosphate under hypoxia. Dihyroorotate, not orotate, is then secreted out of cells. The specific metabolic pathway occurs in vivo and is required for tumor growth. Such a metabolic pathway renders glutamine mainly to acetyl coenzyme A for lipogenesis, with the rest carbon and nitrogen being safely removed. Our results reveal how glutamine carbon and nitrogen are coordinatively metabolized under hypoxia, and provide a comprehensive understanding on glutamine metabolism.\n\nSignificanceTumor cells often addict to glutamine, and particularly utilize its carbon for lipogenesis under hypoxia. We reveal that tumor cells package the excessive glutamine-nitrogen into secretory dihydroorotate, instead of toxic ammonia. This specifically reprogrammed pathway supports in vivo tumor growth, and could offer diagnostic markers and therapeutic targets for cancers.

biochemistry↗

bioRxiv2018

Can we obtain in vivo transmural mean hoop stress of the aortic wall without knowing patient-specific material properties and residual deformations?

It is well known that residual deformations/stresses alter the mechanical behavior of arteries, e.g. the pressure-diameter curves. In an effort to enable personalized analysis of the aortic wall stress, approaches have been developed to incorporate experimentally-derived residual deformations into in vivo loaded geometries in finite element simulations using thick-walled models. Solid elements are typically used to account for \"bending-like\" residual deformations. Yet, the difficulty in obtaining patient-specific residual deformations and material properties has become one of the biggest challenges of these thick-walled models. In thin-walled models, fortunately, static determinacy offers an appealing prospect that allows for the calculation of the thin-walled membrane stress without patient-specific material properties. The membrane stress can be computed using forward analysis by enforcing an extremely stiff material property as penalty treatment, which is referred to as the forward penalty approach. However, thin-walled membrane elements, which have zero bending stiffness, are incompatible with the residual deformations, and therefore, it is often stated as a limitation of thin-walled models. In this paper, by comparing the predicted stresses from thin-walled models and thick-walled models, we demonstrate that the transmural mean hoop stress is the same for the two models and can be readily obtained from in vivo clinical images without knowing the patient-specific material properties and residual deformations. Computation of patient-specific mean hoop stress can be greatly simplified by using membrane model and the forward penalty approach, which may be clinically valuable.

bioengineering↗

bioRxiv2018

Estimation of in vivo constitutive parameters of the aortic wall: a machine learning approach

The patient-specific biomechanical analysis of the aorta demands the in vivo mechanical properties of individual patients. Current inverse approaches have shown the feasibility of estimating the nonlinear, anisotropic material parameters from in vivo image data using certain optimization schemes. However, since such inverse methods are dependent on iterative nonlinear optimization, these methods are highly computation-intensive, which may take weeks to complete for only a single patient, inhibiting rapid feedback for clinical use. Recently, machine learning (ML) techniques have led to revolutionary breakthroughs in many applications. A potential paradigm-changing solution to the bottleneck associated with patient-specific computational modeling is to incorporate ML algorithms to expedite the procedure of in vivo material parameter identification. In this paper, we developed a ML-based approach to identify the material parameters from three-dimensional aorta geometries obtained at two different blood pressure levels, namely systolic and diastolic geometries. The nonlinear relationship between the two loaded shapes and the constitutive parameters are established by a ML-model, which was trained and tested using finite element (FE) simulation datasets. Cross-validation was used to adjust the ML-model structure on a training/validation dataset. The accuracy of the ML-model was examined using a testing dataset.

bioengineering↗