An off-on fluorescence method for acid phosphatase assay based on the inner filter effect of MnO2 nanosheets on vitamin B2.

Fluorescence analysis has attracted much attention due to its rapidity and sensitivity. The present work describes a novel fluorescence detection method for acid phosphatase (ACP) on the basis of inner-filter effect (IFE), where MnO2 nanosheets (MnO2 NSs) and vitamin B2 (VB2) are served as absorbers and fluorophores, respectively. In the absence of ACP, the absorption band of MnO2 NSs overlaps well with the excitation band of VB2, resulting in effective IFE and inhibition of VB2 fluorescence. In the presence of ACP, 2-phospho-L-ascorbic acid trisodium salt (AAP) is hydrolyzed to generate ascorbic acid (AA), which efficiently trigger the reduction of MnO2 NSs into Mn2+ ions, causing the weakening of the MnO2 NSs absorption band and the recovery of VB2 fluorescence. Further investigation indicates that the fluorescence recovery degree of VB2 increases with the increase of ACP concentration. Under selected experimental conditions, the proposed method can achieve sensitive detection of ACP in the ranges of 0.5-4.0 mU/mL and 4.0-15 mU/mL along with a limit of detection (LOD) as low as 0.14 mU/mL. Finally, this method was successfully applied for the detection of ACP in human serum samples with satisfactory recoveries in the range of 95.0 %-108 %.

Induction of perineural invasion in salivary adenoid cystic carcinoma by circular RNA RNF111

Objective Local recurrence, distant metastasis, and perineural invasion (PNI) viciously occur in salivary adenoid cystic carcinoma (SACC), resulting in a poor prognosis. This study aimed to explore the mechanism by which circular RNA RNF111 (circ-RNF111) regulates PNI in SACC by targeting the miR-361-5p/high mobility group box 2 (HMGB2) axis. Method Circ-RNF111 and HMGB2 were highly expressed in SACC specimens, while miR-361-5p was underexpressed. Functional experiments showed that ablating circ-RNF111 or promoting miR-361-5p hindered the biological functions and PNI of SACC-LM cells. Results HMGB2 overexpression induced the reversal of SACC-LM cell biological functions and PNI caused by circ-RNF111 knockout. Furthermore, reduction of circ-RNF111 suppressed PNI in a SACC xenograft model. Circ-RNF111 regulated HMGB2 expression through targeted modulation of miR-361-5p. Conclusion Taken together, circ-RNF111 stimulates PNI in SACC by miR-361-5p/HMGB2 axis and may serve as a potential therapeutic target for SACC (AU)

A modified electrode based on a 3D reduced graphene oxide and MoS2 composite for simultaneous detection of sunset yellow and tartrazine.

A 3D reduced graphene oxide (3DrGO) composite loaded with cauliflower-like MoS2 was prepared. Benefiting from the synergistic effects of 3DrGO and cauliflower-like MoS2, a glassy carbon electrode (GCE) modified with the 3DrGO-MoS2 composite (3DrGO-MoS2/GCE) displays high sensing performance for sunset yellow (SY) and tartrazine (TZ) at working potentials of 0.795 and 1.034 V. Furthermore, a well separated oxidation peak potential can achieve simultaneous detection of the two analytes. Under selected conditions, the peak current exhibits a piecewise linear relationship with the SY concentration in the range of 0.05-10 µmol L-1 and 10-60 µmol L-1, and the plot of peak current versus the TZ concentration also exhibits two linear segments in the range of 0.1-6.0 µmol L-1 and 6.0-60 µmol L-1. The detection limits of SY and TZ are as low as 17.6 and 37.4 nmol L-1, respectively. The prepared 3DrGO-MoS2/GCE was applied for the determination of SY and TZ in food samples with excellent recoveries of 95.1-105.4%.

Induction of perineural invasion in salivary adenoid cystic carcinoma by circular RNA RNF111.

OBJECTIVE: Local recurrence, distant metastasis, and perineural invasion (PNI) viciously occur in salivary adenoid cystic carcinoma (SACC), resulting in a poor prognosis. This study aimed to explore the mechanism by which circular RNA RNF111 (circ-RNF111) regulates PNI in SACC by targeting the miR-361-5p/high mobility group box 2 (HMGB2) axis. METHOD: Circ-RNF111 and HMGB2 were highly expressed in SACC specimens, while miR-361-5p was underexpressed. Functional experiments showed that ablating circ-RNF111 or promoting miR-361-5p hindered the biological functions and PNI of SACC-LM cells. RESULTS: HMGB2 overexpression induced the reversal of SACC-LM cell biological functions and PNI caused by circ-RNF111 knockout. Furthermore, reduction of circ-RNF111 suppressed PNI in a SACC xenograft model. Circ-RNF111 regulated HMGB2 expression through targeted modulation of miR-361-5p. CONCLUSION: Taken together, circ-RNF111 stimulates PNI in SACC by miR-361-5p/HMGB2 axis and may serve as a potential therapeutic target for SACC.

Convergent loss of anthocyanin pigments is controlled by the same MYB gene in cereals.

Loss of anthocyanin pigments is a common transition during cereal domestication, diversification, and improvement. However, the genetic basis for this convergent transition in cereal remains largely unknown. Here, we identified a chromosomal syntenic block across different species that contained R2R3-MYB genes (c1/pl1) responsible for the convergent decoloring of anthocyanins in cereals. Quantitative trait locus (QTL) mapping identified a major QTL for aerial root color corresponding to pl1 and a major QTL for spikelet color corresponding to c1 on maize chromosomes 6 and 9, respectively. One insertion in the regulatory region that led to transcriptional down-regulation was present in maize pl1, and several insertions in the coding region resulting in loss of function occurred in maize c1. A transposable element insertion in the third exon of c1, leading to three new non-functional transcripts, was responsible for decoloring in foxtail millet. The c1/pl1 genes enhanced the transcription of the core enzyme-encoding genes, including pr1, fht1, a1, a2, bz1, and aat1 in the anthocyanin pathway, while they repressed the expression of fnsii1 in flavones, sm2 in maysin, and bx3, bx4, bx5, and bx10 in DIMBOA. Our results indicated that the convergent decoloring of these plants shared the same genetic basis across different cereal species.

Transposon Insertion Drove the Loss of Natural Seed Shattering during Foxtail Millet Domestication.

Loss of seed shattering was a key step during cereal domestication, and it greatly facilitated seed harvest of the staple cereal foxtail millet (Setaria italica) because the cereal has very small seeds. However, the genetic basis for this loss has been largely unknown. Here, we combined comparative and association mapping to identify an 855-bp Harbinger transposable element insertion in the second exon of the foxtail millet gene shattering1 (sh1) that was responsible for the loss of seed shattering. The sh1 gene encodes zinc finger and YABBY domains. The insert prevents transcription of the second exon, causing partial loss of the zinc finger domain and then loss of natural seed shattering. Specifically, sh1 functions as a transcription repressor and represses the transcription of genes associated with lignin synthesis in the abscission zone, including CAD2. The diversity of sh1 is highly reduced in foxtail millet, consistent with either a severe domestication bottleneck or a selective sweep. Phylogenetic analysis of sh1 further revealed a single origin of foxtail millet in China. Our results support the theories that transposons were the most active factors in genome evolution driving loss of natural seed shattering during foxtail millet domestication and that sh1 underwent parallel selection during domestication across different cereal species.

A gene regulatory network for tiller development mediated by Tin8 in maize.

The complex gene regulatory network underlying tiller development in maize remains largely unknown. Here we identified two major quantitative trait loci for tiller number, Tin8 on chromosome 8 and the previously known Tb1 on chromosome 1, in a population derived from a teosinte-maize cross. Map-based cloning and association mapping revealed that Tin8, corresponding to Zcn8 encoding a phosphatidylethanolamine-binding-related kinase, is down-regulated in transcription, which results in decreased tiller number. A strong interaction between Tin8 and the key gen Tb1 was detected for tiller number. Further RNA-seq analysis showed that the expression of 13 genes related to tiller development was controlled by Tin8. Our results support the existence of a complex gene regulatory network for the outgrowth of the tiller bud in maize, in which Zcn8 controls 13 tiller-related genes, including four genes for hormonal responses. In particular, Zcn8 represses Gt1, D14, and Tru1 through the interaction with Tb1.

Gene duplication drove the loss of awn in sorghum.

Loss of the awn in some cereals, including sorghum, is a key transition during cereal domestication or improvement that has facilitated grain harvest and storage. The genetic basis of awn loss in sorghum during domestication or improvement remains unknown. Here, we identified the awn1 gene encoding a transcription factor with the ALOG domain that is responsible for awn loss during sorghum domestication or improvement. awn1 arose from a gene duplication on chromosome 10 that translocated to chromosome 3, recruiting a new promoter from the neighboring intergenic region filled with "noncoding DNA" and recreating the first exon and intron. awn1 acquired high expression after duplication and represses the elongation of awns in domesticated sorghum. Comparative mapping revealed high collinearity at the awn1 paralog locus on chromosome 10 across cereals, and awn growth and development were successfully reactivated on the rice spikelet by inactivating the rice awn1 ortholog. RNA-seq and DAP-seq revealed that as a transcriptional repressor, AWN1 bound directly to a motif in the regulatory regions of three MADS genes related to flower development and two genes, DL and LKS2, involved in awn development. AWN1 downregulates the expression of these genes, thereby repressing awn elongation. The preexistence of regulatory elements in the neighboring intergenic region of awn1 before domestication implicates that noncoding DNA may serve as a treasure trove for evolution during sorghum adaptation to a changing world. Taken together, our results suggest that gene duplication can rapidly drive the evolution of gene regulatory networks in plants.

Opposite response of maize ZmCCT to photoperiod due to transposon jumping.

KEY MESSAGE: The new 4.2-kb transposable insertion in the intron of ZmCCT reversely responded relative to the known 5.1-kb transposable insertion to photoperiods between low- and high-latitude regions. Flowering time is a key trait for cereal adaptation that is controlled by a complex genetic background in maize. The effect of multiple alleles from a quantitative trait locus (QTL) on flowering time remains largely unknown. Here, we fine-mapped a major QTL for flowering time on maize chromosome 10 corresponding to ZmCCT, where a new allele with a 4.2-kilobase (kb) transposable insertion was present in the intron. The known allele with a 5.1-kb transposon insertion in the promoter of ZmCCT enhances flowering in high-latitude regions, but has no effect on flowering time in low-latitude regions in comparison with the null allele lacking this insertion. However, our new allele with a 4.2-kb insertion reduced flowering in the low-latitude region, but produced unchanged flowering time in the high-latitude region relative to the 5.1-kb transposable insertion. Transcription analysis revealed that the new allele with 4.2-kb insertion versus the 5.1-kb insertion repressed and unchanged the transcription of ZmCCT in the low- and high-latitude regions, respectively. Thus, the allele with the 4.2-kb transposable insertion showed a completely opposite response to photoperiods between these two regions. Phylogenetic analysis revealed that the 4.2-kb transposable insertion in the two Northern flint corns originated from tropical maize. RNA-seq analysis and dual-luciferase transient expression assays further identified a conserved gene regulation network of ZmCCT between maize and rice, in which ZmCCT directly repressed the transcription of the florigen gene ZCN8 via ZmEhd1. Our results suggest that transposable elements play an important role in maize adaptation.

Fibulin-3 affects vascular endothelial function and is regulated by angiotensin II.

OBJECTIVE: The aim of the present study was to investigate the effect of fibulin-3 on vascular endothelial function, and to explore the relevant underlying mechanism with regard to the involvement of angiotensin II (AngII). METHODS: One hundred and eight patients with essential hypertension (EH) and 31 controls were included to measure the flow-mediated dilatation (FMD). Serum fibulin-3 and AngII were examined using enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay. Stable transfection of fibulin-3 was conducted on human umbilical vein endothelial cells (HUVECs) and SV40T-transformed HUVECs (PUMC-HUVEC-T1 cells). Cell counting kit-8 assay, cell cycle assay, wound healing assay, Transwell assay, apoptosis assay, and tube formation assay were subsequently performed. The expression of angiogenesis-associated genes [endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor A (VEGFA)] were measured by western blot analysis. HUVECs and PUMC-HUVEC-T1 cells were treated with AngII, and with or without an inhibitor of nuclear factor κB (NF-κB), BAY 11-7082. Pro-inflammatory cytokines [interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)] were detected by ELISA. The expression levels of fibulin-3 and p65 were then measured by western blotting. RESULTS: Lower levels of serum fibulin-3 were accompanied by poorer FMD and higher levels of serum AngII in patients with EH. Fibulin-3 overexpression promoted cell proliferation, migration, and angiogenesis, but led to an inhibition of apoptosis. By contrast, fibulin-3 downregulation inhibited cell proliferation, migration and angiogenesis, but promoted apoptosis. AngII induced inflammation and inhibited the expression of fibulin-3. BAY 11-7082 eliminated the inhibitory effect of AngII on fibulin-3. CONCLUSIONS: Taken together, the results of the present study have shown that serum fibulin-3 may be a predictor of vascular endothelial function in patients with EH. Fibulin-3 gene may also have a beneficial role in repairing the vascular endothelium. Furthermore, the results also suggested that fibulin-3 gene was suppressed by AngII via the NF-κB signaling pathway.

EFEMP1 as a Potential Biomarker for Diagnosis and Prognosis of Osteosarcoma.

Osteosarcoma (OS) is the most common primary bone malignancy. Our previous study revealed an association between the level of epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) and the invasion, metastasis, and poor prognosis of OS. However, the exact correlation between the serum EFEMP1 level and OS diagnosis and progression was unclear. This study is aimed at determining the value of the serum EFEMP1 level in the diagnosis and prognosis of OS. Fifty-one consecutive OS patients were prospectively registered in this study. The serum EFEMP1 levels were measured using ELISA at diagnosis, after neoadjuvant chemotherapy, and before and after surgical treatment. Sixty-nine healthy subjects in the control group, nine patients with chondrosarcoma, and 12 patients with giant cell tumor of the bone were also enrolled in this study. Surgical orthotopic implantation was used to generate a mouse OS model, and the correlation between the circulating EFEMP1 levels and tumor progression was examined. Then, OS patients had significantly higher mean serum EFEMP1 levels (7.61 ng/ml) than the control subjects (1.47 ng/ml). The serum EFEMP1 levels were correlated with the Enneking staging system (r = 0.32, P = 0.021) and lung metastasis (r = 0.50, P < 0.001). There was also a correlation between the serum EFEMP1 level and EFEMP1 expression in the respective OS samples (r = 0.49, P < 0.001). Additionally, patients with either chondrosarcoma or giant cell tumor of the bone had significantly higher serum EFEMP1 levels than OS patients. Surgical and chemotherapeutic treatment led to an increase in the serum EFEMP1 levels. Then, the destruction of bone tissues might be one of the factors about the EFEMP1 levels. In the mouse OS model, the serum EFEMP1 level was correlated with tumor progression. Our results suggested that serum EFEMP1 levels might be used to distinguish OS patients from healthy controls and as an indicator for OS lung metastasis. Serum EFEMP1 levels could serve as a new and assisted biomarker for the auxiliary diagnosis and prognosis of OS.

A Large Transposon Insertion in the stiff1 Promoter Increases Stalk Strength in Maize.

Stalk lodging, which is generally determined by stalk strength, results in considerable yield loss and has become a primary threat to maize (Zea mays) yield under high-density planting. However, the molecular genetic basis of maize stalk strength remains unclear, and improvement methods remain inefficient. Here, we combined map-based cloning and association mapping and identified the gene stiff1 underlying a major quantitative trait locus for stalk strength in maize. A 27.2-kb transposable element insertion was present in the promoter of the stiff1 gene, which encodes an F-box domain protein. This transposable element insertion repressed the transcription of stiff1, leading to the increased cellulose and lignin contents in the cell wall and consequently greater stalk strength. Furthermore, a precisely edited allele of stiff1 generated through the CRISPR/Cas9 system resulted in plants with a stronger stalk than the unedited control. Nucleotide diversity analysis revealed that the promoter of stiff1 was under strong selection in the maize stiff-stalk group. Our cloning of stiff1 reveals a case in which a transposable element played an important role in maize improvement. The identification of stiff1 and our edited stiff1 allele pave the way for efficient improvement of maize stalk strength.

The tin1 gene retains the function of promoting tillering in maize.

Sweet maize and popcorn retain tillering growth habit during maize diversification. However, the underlying molecular genetic mechanism remains unknown. Here, we show that the retention of maize tillering is controlled by a major quantitative trait locus (QTL), tin1, which encodes a C2H2-zinc-finger transcription factor that acts independently of tb1. In sweet maize, a splice-site variant from G/GT to C/GT leads to intron retention, which enhances tin1 transcript levels and consequently increases tiller number. Comparative genomics analysis and DNA diversity analysis reveal that tin1 is under parallel selection across different cereal species. tin1 is involved in multiple pathways, directly represses two tiller-related genes, gt1 and Laba1/An-2, and interacts with three TOPLESS proteins to regulate the outgrowth of tiller buds. Our results support that maize tin1, derived from a standing variation in wild progenitor teosinte population, determines tillering retention during maize diversification.

Genetic Architecture of domestication- and improvement-related traits using a population derived from Sorghum virgatum and Sorghum bicolor.

The genetic basis of domestication and improvement remains largely unknown in sorghum as a typical multiple-origins species. In this study, the F2 and F3 populations derived from a cross between Sorghum virgatum and domesticated sorghum were used to study the genetic architecture of domestication- and improvement-related traits. We found that human selection had greatly reshaped sorghum through the Quantitative Trait Loci (QTLs) with large genetic effects in the traits of harvest, plant architecture and grain taste including the reduction of shattering, few branches, short plant stature and the removal of polyphenols from seed. The expansion of seed width was selected to improve the yield through accumulating small-effect QTLs. Two major QTLs of plant height (QTI-ph1 and dw1) were narrowed down into 24.5-kilobase (kb) and 13.9-kb, respectively. DNA diversity analysis and association mapping of dw1 gene suggested the functional variant (A1361 T) might originate from the same event not long time ago. Our results supported that parallel phenotypic changes across different species during domestication and improvement might share the same genetic basis, QTL × QTL interactions might not play an important role in the reshaping of traits during sorghum domestication and improvement, and offered new views on transgressive segregation and segregation distortion. Our study greatly deepens our understandings of the genetic basis of sorghum domestication and improvement.

krn1, a major quantitative trait locus for kernel row number in maize.

Kernel row number is a fundamental component of maize (Zea mays) yield and an important target for maize breeding. The revolutionary transition from the two-rowed teosinte to maize with increased kernel row numbers dramatically enhanced yields during domestication. Kernel row number is controlled by many quantitative trait loci (QTLs), however most genes responsible for these QTLs remain uncharacterised and the molecular genetic mechanisms are unknown. Here, we combined map-based cloning and association mapping to identify a major QTL for kernel row number, krn1, which is likely to correspond to an existing gene (ids1/Ts6) encoding an AP2 domain protein homologous to the product of the wheat key domestication gene Q. The increased expression of ids1/Ts6 in two maize mutants increased spikelet pair meristem numbers and then enhanced kernel row numbers. Nucleotide diversity analysis further revealed that ids1/Ts6 and Q were under strong parallel selection in maize and wheat that increased their yields during domestication or improvement. RNA-seq revealed that ids1/Ts6 is involved in multiple pathways regulating spikelet pair meristem development, involving several key genes such as fea3, fea4 and ra3. The cloning of the krn1 gene will pave a new way to efficiently improve maize yield in the near future.

Parallel Stochastic Discrete Event Simulation of Calcium Dynamics in Neuron.

The intra-cellular calcium signaling pathways of a neuron depends on both biochemical reactions and diffusions. Some quasi-isolated compartments (e.g., spines) are so small and calcium concentrations are so low that one extra molecule diffusing in by chance can make a nontrivial difference in concentration (percentage-wise). These rare events can affect dynamics discretely in such a way that they cannot be evaluated by a deterministic and continuous simulation. Stochastic models of such a system provide a more detailed understanding of these systems than existing deterministic models because they capture their behavior at a molecular level. Our research focuses on the development of a high performance parallel discrete event simulation environment, Neuron Time Warp (NTW), which is intended for use in the parallel simulation of stochastic reaction-diffusion systems such as intra-calcium signaling. NTW is integrated with NEURON, a simulator which is widely used within the neuroscience community. We simulate two models, a calcium buffer and a calcium wave model. The calcium buffer model is employed in order to verify the correctness and performance of NTW by comparing it to a sequential deterministic simulation in NEURON. We also derived a discrete event calcium wave model from a deterministic model using the stochastic $\text{IP}_{3}\text{R}$IP3R structure.

QTL mapping in a maize F2 population using Genotyping-by-Sequencing and a modified fine-mapping strategy.

Maize possesses a tremendous genetic diversity, most of which is deposited in a large number of landraces. However, the genetic basis of local diversity from maize landrace remains largely unknown. Traditional fine mapping of the causal gene for complex trait, based on the transition from the quantitative trait locus (QTL) to a single qualitative gene through backcrossing or the construction of heterogeneous inbred family (HIF), has achieved great success in model crop rice. However, this fine-mapping strategy did not work well in maize. In this study, an F2 population derived from a maize landrace and an elite inbred line was firstly genotyped by genotyping by sequencing (GBS). QTL analysis further revealed 29 QTLs of 12 traits, most of which individually accounted for more than 10% of phenotypic variations. Next traditional fine-mapping method successfully narrowed down a major QTL of kernel color qCOK1, but failed in the fine mapping of another major QTL of ear height EH4 because the EH4 remained quantitative feature in the HIF. Based on the quantitative feature of the EH4 in the HIF, we then performed the correlation tests between genotypes and phenotypes in the descendant populations derived from the recombination plants to enable the process of fine mapping. Our modified fine-mapping strategy successfully narrowed down the EH4 into a 3.23-Mb region on chromosome 8. The modified fine-mapping method can be applied to fast clone the QTLs originated from maize landraces.

A new allele of the Brachytic2 gene in maize can efficiently modify plant architecture.

The applications of semi-dwarf genes such as sd1 and Rht1 in rice and wheat resulted in the first "green revolution" in the 1960s. However, such semi-dwarf genes that can efficiently reduce plant stature and have few negative yield traits have not yet been identified in maize. In this study, a new allele of Brachytic2 gene (qpa1) encoding P-glycoprotein was rapidly fine-mapped using a modified method. The qpa1, containing a 241-bp deletion in the last exon, had no negative effect on yield, but greatly modified the plant architecture including significantly reduced plant height and ear height, increased stalk diameter and erected leaf. A common variant similar to maize qpa1 was also present in the sorghum orthologous dw3 locus. Comparative RNA-seq analysis next showed 99 differentially co-expressed genes affected by Br2 in maize and dw3 in sorghum, including four plant height genes D3, BAK1, Actin7 and Csld1, which are involved in gibberellin and brassinosteroid biosynthesis, auxin transport and cellulose synthesis. The qpa1 can be applied to efficiently modify plant stature in maize and in combination with D3, BAK1, Actin7, Csld1 and the other 95 differentially co-expressed genes, can be edited using new genomic editing tools for further applications and studies.

The genetic architecture of nodal root number in maize.

The maize nodal root system plays a crucial role in the development of the aboveground plant and determines the yield via the uptake of water and nutrients in the field. However, the genetic architecture of the maize nodal root system is not well understood, and it has become the 'dark matter' of maize genetics. Here, a large teosinte-maize population was analyzed, and high-resolution mapping revealed that 62 out of 133 quantitative trait loci (QTLs), accounting for approximately half of the total genetic variation in nodal root number, were derived from QTLs for flowering time, which was further validated through a transgenic analysis and a genome-wide association study. However, only 16% of the total genetic variation in nodal root number was derived from QTLs for plant height. These results gave a hint that flowering time played a key role in shaping nodal root number via indirect selection during maize domestication. Our results also supported that more aerial nodal roots and fewer crown roots might be favored in temperate maize, and this root architecture might efficiently improve root-lodging resistance and the ability to take up deep water and nitrogen under dense planting.

Load balancing for multi-threaded PDES of stochastic reaction-diffusion in neurons.

Stochastic simulation of chemical reactions and diffusion in a neuron helps to provide a realistic view of the molecular dynamics within a neuron. We developed a multi-threaded PDES simulator, Neuron Time Warp-Multi Thread, suitable for the stochastic simulation of reaction and diffusion in a neuron. In this paper we make use of Q-Learning and Simulated Annealing to determine the parameters for a dynamic load balancing algorithm and for dynamic window control. During the simulation, the runtime statistics of each thread are collected and used to determine the execution time of the simulation. Based upon this assessment, workload is migrated from the most overloaded threads to the most under-load ones. As the results for a calcium wave model show, both approaches can improve the execution time for small simulations by up to 31% (Q-Learning) and 19% (SA). The simulated annealing approach is more suitable for larger populations, decreasing execution time by 41%.