Genetic Model Research Articles

Hydrogeochemical Evolution, Isotopic Insights, and Genetic Models of Geothermal Water in Anhui Province, China

Anhui Province is rich in geothermal water resources, making the study of its hydrochemical evolution and genetic models essential for scientific development and sustainable utilization. This study combines hydrochemical and hydrogen–oxygen isotopic data from different regions of Anhui Province to analyze the hydrogeochemical evolution characteristics and recharge mechanisms of basin-type and mountainous-type geothermal waters. The results show that basin-type geothermal water is predominantly of the Cl–Na type, with water–rock interactions mainly including halite dissolution, gypsum dissolution, dedolomitization, and silicate hydrolysis. The groundwater system is relatively closed off, with slow flow rates. In contrast, mountainous geothermal water is mainly of the HCO3–Na·Ca, SO4–Na·Ca, and SO4–Na types, with water–rock interactions primarily involving calcite dissolution, dolomite dissolution, and gypsum dissolution. Enhanced precipitation infiltration due to fault structures leads to stronger recharge and an open-system characteristic. The genetic models of the two types of geothermal water reveal the structural and recharge mechanisms of thermal reservoirs under different geological settings, highlighting the significant control of geological background on geothermal water formation.

Activin A receptor type 1C single nucleotide polymorphisms associated with esophageal squamous cell carcinoma risk in Chinese population

BACKGROUND Transforming growth factor-β (TGF-β) superfamily plays an important role in tumor progression and metastasis. Activin A receptor type 1C (ACVR1C) is a TGF-β type I receptor that is involved in tumorigenesis through binding to different ligands. AIM To evaluate the correlation between single nucleotide polymorphisms (SNPs) of ACVR1C and susceptibility to esophageal squamous cell carcinoma (ESCC) in Chinese Han population. METHODS In this hospital-based cohort study, 1043 ESCC patients and 1143 healthy controls were enrolled. Five SNPs (rs4664229, rs4556933, rs77886248, rs77263459, rs6734630) of ACVR1C were assessed by the ligation detection reaction method. Hardy-Weinberg equilibrium test, genetic model analysis, stratified analysis, linkage disequilibrium test, and haplotype analysis were conducted. RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC, and those with rs77886248 TA mutant were related with higher risk, especially in older male smokers. In the haplotype analysis, ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC, while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC. CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC, which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.

Associations of RANKL levels and polymorphisms with rheumatoid arthritis: A meta-analysis.

This study examined the correlation between circulating receptor activator for nuclear factor-κB ligand (RANKL) levels and rheumatoid arthritis (RA), and investigated the association between polymorphisms in the RANKL gene and susceptibility to RA. We searched the Medline, Embase, and Cochrane databases for relevant publications up to September 2024. A meta-analysis was conducted to assess serum/plasma RANKL levels in patients with RA and controls, and to explore the relationship between RANKL rs9533156 and rs2277438 polymorphisms and RA susceptibility. Ten studies encompassing 1,682 RA patients and 1,288 controls were analyzed. RANKL levels were significantly higher in RA patients compared to controls (SMD = 0.665, 95% CI = 0.290-1.040, P = 0.001). Subgroup analysis affirmed these findings' consistency across different sample sizes and publication years. RANKL levels were positively associated with rheumatoid factor (RF) and Disease Activity Score-28 (DAS28) (RF correlation coefficient = 0.157, 95% CI = 0.028-0.282, P = 0.018; DAS28 correlation coefficient = 0.151, 95% CI = 0.125-0.370, P < 0.001). Additionally, the meta-analysis revealed significant associations between the susceptibility to RA and the RANKL rs9533156 C allele (OR = 0.609, 95% CI = 0.520-0.714, P < 0.010) as well as the rs2277438 G allele (OR = 1.206, 95% CI = 1.003-1.451, P = 0.047). These associations were consistent across homozygote comparisons and different genetic models. This meta-analysis underscores the elevated circulating RANKL levels in RA patients and their significant correlation with RF and DAS28. Additionally, the RANKL rs9533156 and rs2277438 polymorphisms were significantly associated with RA susceptibility.

Inhibited peroxidase activity of peroxiredoxin 1 by palmitic acid exacerbates nonalcoholic steatohepatitis in male mice

Reactive oxygen species exacerbate nonalcoholic steatohepatitis (NASH) by oxidizing macromolecules; yet how they promote NASH remains poorly understood. Here, we show that peroxidase activity of global hepatic peroxiredoxin (PRDX) is significantly decreased in NASH, and palmitic acid (PA) binds to PRDX1 and inhibits its peroxidase activity. Using three genetic models, we demonstrate that hepatic PRDX1 protects against NASH in male mice. Mechanistically, PRDX1 suppresses STAT signaling and protects mitochondrial function by scavenging hydrogen peroxide, and mitigating the oxidation of protein tyrosine phosphatases and lipid peroxidation. We further identify rosmarinic acid (RA) as a potent agonist of PRDX1. As revealed by the complex crystal structure, RA binds to PRDX1 and stabilizes its peroxidatic cysteine. RA alleviates NASH through specifically activating PRDX1’s peroxidase activity. Thus, beyond revealing the molecular mechanism underlying PA promoting oxidative stress and NASH, our study suggests that boosting PRDX1’s peroxidase activity is a promising intervention for treating NASH.

CURRENT ISSUES OF MODELING HEART FAILURE AND MYOCARDIAL FIBROSIS IN RATS

HighlightsMethods for modeling heart failure in rats are classified into models requiring surgical intervention, toxic, genetic and autoimmune models, models based on the effects of physical factors, the use of special dietary regimens.It is impossible to single out a single ideal model, since the development of heart failure is a multifactorial process, it is preferable to use a combination of several methods.The correctness of the choice of the model and its compliance with the tasks of future research must be confirmed by combining several diagnostic methods for verifying myocardial fibrosis - laboratory, histological, instrumental. AnnotationDetailed study of the mechanisms of heart failure and its main pathogenetic factor, myocardial fibrosis, is required for developing new effective treatment strategies. The choice of an appropriate model is key for a reliable experimental study. The aim of the review is to systematize current data on methods for modeling heart failure in rats. The main advantages of these animals are high genetic, biochemical and physiological similarity with humans, ease of breeding, availability of maintenance, small size, while allowing for surgery. This article classifies the currently available rat models of heart failure, discusses their pathophysiological basis, timing of the formation of heart failure, clinical features, advantages and disadvantages of each experimental model. The authors have paid particular attention to methods developed by domestic scientists. Methods for assessing the developed myocardial fibrosis and the influence of drugs on its formation are considered. The study of heart failure requires reliable animal models to assess biochemical, functional, morphological changes in damaged myocardium, and controlled testing of new drugs. Should the necessity arise, specialists should use several methods simultaneously, whereas the choice of treatment strategy depends on the aim of the study.

Unveiling shared genetic regulators of plant architectural and biomass yield traits in sorghum.

Sorghum is emerging as an ideal genetic model for designing high-biomass bioenergy crops. Biomass yield, a complex trait influenced by various plant architectural characteristics, is typically regulated by numerous genes. This study aimed to dissect the genetic regulators underlying fourteen plant architectural traits and ten biomass yield traits in the Sorghum Association Panel across two growing seasons. We identified 321 associated loci through genome-wide association studies (GWAS), involving 234,264 single nucleotide polymorphisms (SNPs). These loci include genes with known associations to biomass traits, such as 'maturity', 'dwarfing (Dw)', and 'leafbladeless1', as well as several uncharacterized loci not previously linked to these traits. We also identified 22 pleiotropic loci associated with variation in multiple phenotypes. Three of these loci, located on chromosomes 3 (S03_15463061), 6 (S06_42790178; Dw2), and 9 (S09_57005346; Dw1), exerted significant and consistent effects on multiple traits across both growing seasons. Additionally, we identified three genomic hotspots on chromosomes 6, 7, and 9, each containing multiple SNPs associated with variation in plant architecture and biomass yield traits. Chromosome-wise correlation analyses revealed multiple blocks of positively associated SNPs located near or within the same genomic regions. Finally, genome-wide correlation-based network analysis showed that loci associated with flowering, plant heights, leaf traits, plant density, and tiller number per plant were highly interconnected with other genetic loci influencing with plant architectural and biomass yield traits. The pyramiding of favorable alleles related to these traits holds promise for enhancing the future development of bioenergy sorghum crops.

A membrane-targeted photoswitch restores physiological ON/OFF responses to light in the degenerate retina

The lack of effective therapies for visual restoration in Retinitis pigmentosa and macular degeneration has led to the development of new strategies, such as optogenetics and retinal prostheses. However, visual restoration is poor due to the massive light-evoked activation of retinal neurons, regardless of the segregation of visual information in ON and OFF channels, which is essential for contrast sensitivity and spatial resolution. Here, we show that Ziapin2, a membrane photoswitch that modulates neuronal capacitance and excitability in a light-dependent manner, is capable of reinstating, in mouse and rat genetic models of photoreceptor degeneration, brisk and sluggish ON, OFF, and ON-OFF responses in retinal ganglion cells evoked by full-field stimuli, with reactivation of their excitatory and inhibitory conductances. Intravitreally injected Ziapin2 in fully blind rd10 mice restores light-driven behavior and optomotor reflexes. The results indicate that Ziapin2 is a promising molecule for reinstating physiological visual responses in the late stages of retinal degeneration.

Genetic variations in IGF2BP2 and CAPN10 and their interaction with environmental factors increase gestational diabetes mellitus risk in Chinese women.

This study aims to investigate the association of the genetic variations in IGF2BP2 and CAPN10 as well as gene-environment interactions with the risk of gestational diabetes (GDM) in Chinese women. A total of 1,566 pregnant Chinese women participated in this case-control study. We employed targeted next-generation sequencing to analyze specific SNPs in IGF2BP2 (rs11927381, rs1470579, rs4402960, rs7640539) and CAPN10/rs2975760. Various genetic models were used to assess the associations of these polymorphisms with GDM risk. Gene-gene and gene-environment interactions were examined using GMDR to identify interaction models, Subsequently, logistic regression was employed to confirm the significance of these models and to evaluate their impact on GDM susceptibility. Our study identified significant associations between the C allele of IGF2BP2/rs11927381 and an increased GDM susceptibility in both dominant (P = 0.031, OR = 1.247) and heterozygote (P = 0.043, OR = 1.239) gene models. Conversely, the heterozygote TC genotype of CAPN10/rs2975760 was associated with a reduced risk of GDM (P = 0.046, OR = 0.766). Increased BMI and O3 levels were linked to a higher GDM susceptibility. We discovered interactions between CAPN10/rs2975760 CC and IGF2BP2/rs11927381 TC genotype that exacerbated GDM risk (P = 0.022, OR = 11.337). Furthermore, interactions between IGF2BP2/rs11927381 and environmental factors were observed, indicating increased GDM risks (BMI: P = 0.004, OR = 1.011; O3: P = 0.013, OR = 1.002; PM2.5: P = 0.042, OR = 1.005；BC: P = 0.048, OR = 1.094; NO3-:P = 0.045, OR = 1.024). GDM is significantly associated with IGF2BP2/rs11927381 and CAPN10/rs2975760 polymorphisms as well as exposure to O3. Furthermore, the interaction between the CAPN10/rs2975760 CC genotype and IGF2BP2/rs11927381 TC genotype, as well as environmental factors (O3, PM2.5, BMI), significantly increases the risk of GDM in Chinese women.

Constitutive deletion of the obscurin-Ig58/59 domains induces atrial remodeling and Ca2+-based arrhythmogenesis.

Obscurin is a giant protein that coordinates diverse aspects of striated muscle physiology. Obscurin immunoglobulin domains 58/59 (Ig58/59) associate with essential sarcomeric and Ca2+ cycling proteins. To explore the pathophysiological significance of Ig58/59, we generated the Obscn-ΔIg58/59 mouse model, expressing obscurin constitutively lacking Ig58/59. Males in this line develop atrial fibrillation by 6-months, with atrial and ventricular dilation by 12-months. As Obscn-ΔIg58/59 left ventricles at 6-months exhibit no deficits in sarcomeric ultrastructure or Ca2+ signaling, we hypothesized that susceptibility to arrhythmia may emanate from the atria. Ultrastructural evaluation of male Obscn-ΔIg58/59 atria uncovered prominent Z-disk streaming by 6-months and further misalignment by 12-months. Relatedly, isolated Obscn-ΔIg58/59 atrial cardiomyocytes exhibited increased Ca2+ spark frequency and age-specific alterations in Ca2+ cycling dynamics, coinciding with arrythmia onset and progression. Quantitative analysis of the transverse-axial tubule (TAT) network using super-resolution microscopy demonstrated significant TAT depletion in Obscn-ΔIg58/59 atria. These structural and Ca2+ signaling deficits were accompanied by age-specific alterations in the expression and/or phosphorylation of T-cap, which links transverse-tubules to Z-disks, and junctophilin-2, which connects transverse-tubules to the sarcoplasmic reticulum. Collectively, our work establishes the Obscn-ΔIg58/59 model as a reputable genetic model for atrial cardiomyopathy and provides mechanistic insights into atrial fibrillation and remodeling.

Region-specific roles of oviductal motile cilia in oocyte/embryo transport and fertility

Abstract The physiological and clinical importance of motile cilia in reproduction is well recognized, however, the specific role they play in transport through the oviduct and how ciliopathies lead to subfertility and infertility is still unclear. The contribution of cilia beating, fluid flow, and smooth muscle contraction to overall progressive transport within the oviduct remains under debate. Therefore, we investigated the role of cilia in the oviduct transport of preimplantation eggs and embryos using a combination of genetic and advanced imaging approaches. We show that the region of the oviduct where cumulus-oocyte complex circling occurs, around the time of fertilization, is correlated with asymmetrical mucosal fold arrangement and non-radially distributed ciliated epithelium. Our results suggest that motile cilia, as well as mucosal fold asymmetry, may contribute to the local flow fields that help steer luminal contents away from the epithelial walls. We also present in vivo, volumetric evidence of delayed egg transport in a genetic mouse model with disrupted motile cilia function in the female reproductive system. Females with Dnah5 deleted in the oviduct epithelium are subfertile and demonstrate disrupted motile cilia activity within the oviduct mucosa. 50% of Dnah5 mutant females have delayed egg transport where COCs did not progress to the ampulla at the expected time-point and remained within the ovarian bursa. The integration of advanced imaging with genetic dysfunction of motile cilia activity provides valuable insights into oviductal transport processes. Potentially, these data could be valuable for better understanding and management of tubal pathologies and human infertility.

Free and forced vibrations of circular plates made of functionally graded graphene origami-enabled auxetic metamaterials

Presented herein is a numerical investigation into the free and forced vibrational characteristics of circular plates made of functionally graded graphene origami-enabled auxetic metamaterials (FG-GOEAMs). The material properties of FG-GOEAM are estimated using genetic programing-assisted micromechanical models considering two graphene content distribution patterns. The effects of graphene content, size and folding degree on the material properties are taken into account by the models. The formulation of the paper is in the context of first-order shear deformation plate theory, and the governing equations of motion are achieved utilizing Hamilton’s principle. In the solution approach, the variational differential quadrature (VDQ) method is employed by which the variational statement of problem is directly derived and discretized using matrix differential and integral operators. Selected numerical results are presented to study the effects of graphene origami (GOri) content, folding degree, and distribution pattern on the free and forced vibration responses of FG-GOEAM circular plates with clamped and hinged boundary conditions.

The value of a metabolic and immune-related gene signature and adjuvant therapeutic response in pancreatic cancer

BackgroundPancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by a dismal prognosis. Treatment outcomes exhibit substantial variability across patients, underscoring the urgent need for robust predictive models to effectively estimate survival probabilities and therapeutic responses in PDAC.MethodsMetabolic and immune-related genes exhibiting differential expression were identified using the TCGA-PDAC and GTEx datasets. A genetic prognostic model was developed via univariable Cox regression analysis on a training cohort. Predictive accuracy was assessed using Kaplan-Meier (K-M) curves, calibration plots, and ROC curves. Additional analyses, including GSAE and immune cell infiltration studies, were conducted to explore relevant biological mechanisms and predict therapeutic efficacy.ResultsAn 8-gene prognostic model (AK2, CXCL11, TYK2, ANGPT4, IL20RA, MET, ENPP6, and CA12) was established. Three genes (AK2, ENPP6, and CA12) were associated with metabolism, while the others were immune-related. Most genes correlated with poor prognosis. Validation in TCGA-PDAC and GSE57495 datasets demonstrated robust performance, with AUC values for 1-, 3-, and 5-year OS exceeding 0.7. The model also effectively predicted responses to adjuvant therapy.ConclusionThis 8-gene signature enhances prognostic accuracy and therapeutic decision-making in PDAC, offering valuable insights for clinical applications and personalized treatment strategies.

Expansion microscopy reveals neural circuit organization in genetic animal models.

Expansion microscopy is a super-resolution technique in which physically enlarging the samples in an isotropic manner increases inter-molecular distances such that nano-scale structures can be resolved using light microscopy. This is particularly useful in neuroscience as many important structures are smaller than the diffraction limit. Since its invention in 2015, a variety of expansion microscopy protocols have been generated and applied to advance knowledge in many prominent organisms in neuroscience, including zebrafish, mice, Drosophila, and Caenorhabditis elegans. We review the last decade of expansion microscopy-enabled advances with a focus on neuroscience.

Transcription factor 7-like 2 (TCF7l2) regulates CNS myelination separating from its role in upstream oligodendrocyte differentiation.

Oligodendrocyte progenitor cells (OPCs) differentiation into oligodendrocytes (OLs) and subsequent myelination are two closely coordinated yet differentially regulated steps for myelin formation and repair in the CNS. Previously thought as an inhibitory factor by activating Wnt/beta-catenin signaling, we and others have demonstrated that the Transcription factor 7-like 2 (TCF7l2) promotes OL differentiation independent of Wnt/beta-catenin signaling activation. However, it remains elusive if TCF7l2 directly controls CNS myelination separating from its role in upstream oligodendrocyte differentiation. This is partially because of the lack of genetic animal models that could tease out CNS myelination from upstream OL differentiation. Here, we report that constitutively depleting TCF7l2 transiently inhibited oligodendrocyte differentiation during early postnatal development, but it impaired CNS myelination in the long term in adult mice. Using time-conditional and developmental-stage-specific genetic approaches, we further showed that depleting TCF7l2 in already differentiated OLs did not impact myelin protein gene expression nor oligodendroglial populations, instead, it perturbed CNS myelination in the adult. Therefore, our data convincingly demonstrate the crucial role of TCF7l2 in regulating CNS myelination independent of its role in upstream oligodendrocyte differentiation.

A genetic algorithm model for route optimisation of cold chain product transportation using vehicles

A genetic algorithm model for route optimisation of cold chain product transportation using vehicles

Antagonisation of Prokineticin Receptor‐2 Attenuates Preeclampsia Symptoms

ABSTRACTPreeclampsia (PE) is the most threatening pathology of human pregnancy. Placenta from PE patients releases harmful factors that contribute to the exacerbation of the disease. Among these factors is the prokineticin1 (PROK1) and its receptor, PROKR2 that we identified as a mediators of PE. Here we tested the effects of PKRA, an antagonist of PROKR2, on the attenuation of PE symptoms. We used the genetic PE mouse model, STOX1 that overexpresses Stox1 gene in a heterozygosis manner in the placenta. This model allowed exploiting two genotypes of the offspring, those that overexpress the Stox1 gene, and the WT that grow in a PE environment (STE). We characterised the effect PKRA (1 μM) on the attenuation of PE symptoms and compared its effects on STOX1 and STE placentas. We also used STOX1 overexpressing trophoblast cells to decipher the PROK1‐underlying mechanism. We demonstrated that (i) antagonisation of PROKR2 attenuated PE‐mediated hypertension and proteinuria, (ii) STE placentas and foetuses exhibited better outcomes in response to PKRA, (iii) the secretome of STOX1‐trophoblasts impacted the integrity of the fetal vasculature that was attenuated by PKRA treatment. This study demonstrates the direct involvement of the PROK1 in PE and identifies PKRA as a promising therapy for PE.

Advancing de novo lipogenesis: Genetic and metabolic insights.

De novo lipogenesis (DNL) is the process whereby cells synthesize fatty acids from acetyl-CoA, contributing to steatosis in fatty liver disease. Two new studies, using genetic mouse models, metabolomics, and pharmacology, identified alternative pathways in DNL and unexpected physiological effects when targeting key enzymes in this pathway.

Role of peroxisome proliferator-activated receptors α and γ in mediating the beneficial effects of β-caryophyllene in a rat model of fragile X syndrome.

β-Caryophyllene (BCP) is a naturally occurring sesquiterpene found in numerous plant species, including Cannabis sativa. BCP has shown a high safety profile and a wide range of biological functions, including beneficial effects in neurodegenerative and inflammatory diseases. Here, we used behavioral, pharmacological, and in-silico docking analyses to investigate the effects and mechanism of action of BCP in Fragile X Syndrome (FXS), the most common inherited cause of Autism Spectrum Disorder (ASD) and intellectual disability. To this aim, we used the recently validated Fmr1-Δexon 8 rat model of FXS, that is also a genetic rat model of ASD. Acute and repeated oral administration of BCP rescued the cognitive deficits displayed by Fmr1-Δexon 8 rats, without inducing tolerance after repeated administration. These beneficial effects were mediated by activation of hippocampal peroxisome proliferator-activated receptors (PPARs) α and γ, and were mimicked by the PPARα agonist Fenofibrate and the PPARγ agonist Pioglitazone. Conversely, CB2 cannabinoid receptors were not involved. Docking analyses further confirmed the ability of BCP to bind rat PPARs. Together, our findings demonstrate that hippocampal PPARs α and γ play a role in the cognitive deficits observed in a rat model of FXS, and provide first preclinical evidence about the efficacy and mechanism of action of BCP in neurodevelopmental disorders.

Corticostriatal maldevelopment in the R6/2 mouse model of juvenile Huntington's disease.

There is a growing consensus that brain development in Huntington's disease (HD) is abnormal, leading to the idea that HD is not only a neurodegenerative but also a neurodevelopmental disorder. Indeed, structural and functional abnormalities have been observed during brain development in both humans and animal models of HD. However, a concurrent study of cortical and striatal development in a genetic model of HD is still lacking. Here we report significant alterations of corticostriatal development in the R6/2 mouse model of juvenile HD. We examined wildtype (WT) and R6/2 mice at postnatal (P) days 7, 14, and 21. Morphological examination demonstrated early structural and cellular alterations reminiscent of malformations of cortical development, and ex vivo electrophysiological recordings of cortical pyramidal neurons (CPNs) demonstrated significant age- and genotype-dependent changes of intrinsic membrane and synaptic properties. In general, R6/2 CPNs had reduced cell membrane capacitance and increased input resistance (P7 and P14), along with reduced frequency of spontaneous excitatory and inhibitory synaptic events during early development (P7), suggesting delayed cortical maturation. This was confirmed by increased occurrence of GABAA receptor-mediated giant depolarizing potentials at P7. At P14, the rheobase of CPNs was significantly reduced, along with increased excitability. Altered membrane and synaptic properties of R6/2 CPNs recovered progressively, and by P21 they were similar to WT CPNs. In striatal medium-sized spiny neurons (MSNs), a different picture emerged. Intrinsic membrane properties were relatively normal throughout development, except for a transient increase in membrane capacitance at P14. The first alterations in MSNs synaptic activity were observed at P14 and consisted of significant deficits in GABAergic inputs, however, these also were normalized by P21. In contrast, excitatory inputs began to decrease at this age. We conclude that the developing HD brain is capable of compensating for early developmental abnormalities and that cortical alterations precede and are a main contributor of striatal changes. Addressing cortical maldevelopment could help prevent or delay disease manifestations.

In Silico Validation of Non-Invasive Arterial Compliance Estimation and Potential Determinants of its Variability

Arterial compliance (AC) is an important cardiovascular parameter characterizing mechanical properties of arteries. AC is significantly influenced by arterial wall structure and vasomotion, and it markedly influences cardiac load. A new method, based on a two-element Windkessel model, has been recently proposed for estimating AC as the ratio of the time constant τ of the diastolic blood pressure decay and peripheral vascular resistance derived from clinically available stroke volume measurements and selected peripheral blood pressure parameters which are less prone to peripheral distortions. The aim of this study was to validate AC estimation using a virtual population generated by in silico model of the systemic arterial tree. In the second part of study, we analysed causal coupling between AC oscillations and variability of its potential determinants – systolic blood pressure and heart rate in healthy young human subjects. The pool of virtual subjects (n=3818) represented an extensive AC distribution. AC was estimated from the peripheral blood pressure curve and by the standard method from the aortic blood pressure curve. The proposed method slightly overestimated AC set in the model but both ACs were strongly correlated (r=0.94, p&lt;0.001). In real data, we observed that AC dynamics was coupled with basic cardiovascular parameters variability independently of the autonomic nervous system state. In silico analysis suggests that AC can be reliably estimated by noninvasive method. The analysis of short-term AC variability together with its determinants could improve our understanding of factors involved in AC dynamics potentially improving assessment of AC changes associated with atherosclerosis process.