Structural basis and regulation of the reductive stress response.

Although oxidative phosphorylation is best known for producing ATP, it also yields reactive oxygen species (ROS) as invariant byproducts. Depletion of ROS below their physiological levels, a phenomenon known as reductive stress, impedes cellular signaling and has been linked to cancer, diabetes, and cardiomyopathy. Cells alleviate reductive stress by ubiquitylating and degrading the mitochondrial gatekeeper FNIP1, yet it is unknown how the responsible E3 ligase CUL2FEM1B can bind its target based on redox state and how this is adjusted to changing cellular environments. Here, we show that CUL2FEM1B relies on zinc as a molecular glue to selectively recruit reduced FNIP1 during reductive stress. FNIP1 ubiquitylation is gated by pseudosubstrate inhibitors of the BEX family, which prevent premature FNIP1 degradation to protect cells from unwarranted ROS accumulation. FEM1B gain-of-function mutation and BEX deletion elicit similar developmental syndromes, showing that the zinc-dependent reductive stress response must be tightly regulated to maintain cellular and organismal homeostasis.

A Cellular Mechanism to Detect and Alleviate Reductive Stress.

Metazoan organisms rely on conserved stress response pathways to alleviate adverse conditions and preserve cellular integrity. Stress responses are particularly important in stem cells that provide lifetime support for tissue formation and repair, but how these protective systems are integrated into developmental programs is poorly understood. Here we used myoblast differentiation to identify the E3 ligase CUL2FEM1B and its substrate FNIP1 as core components of the reductive stress response. Reductive stress, as caused by prolonged antioxidant signaling or mitochondrial inactivity, reverts the oxidation of invariant Cys residues in FNIP1 and allows CUL2FEM1B to recognize its target. The ensuing proteasomal degradation of FNIP1 restores mitochondrial activity to preserve redox homeostasis and stem cell integrity. The reductive stress response is therefore built around a ubiquitin-dependent rheostat that tunes mitochondrial activity to redox needs and implicates metabolic control in coordination of stress and developmental signaling.

Fatty Acids Regulate Germline Sex Determination through ACS-4-Dependent Myristoylation.

Fat metabolism has been linked to fertility and reproductive adaptation in animals and humans, and environmental sex determination potentially plays a role in the process. To investigate the impact of fatty acids (FA) on sex determination and reproductive development, we examined and observed an impact of FA synthesis and mobilization by lipolysis in somatic tissues on oocyte fate in Caenorhabditis elegans. The subsequent genetic analysis identified ACS-4, an acyl-CoA synthetase and its FA-CoA product, as key germline factors that mediate the role of FA in promoting oocyte fate through protein myristoylation. Further tests indicated that ACS-4-dependent protein myristoylation perceives and translates the FA level into regulatory cues that modulate the activities of MPK-1/MAPK and key factors in the germline sex-determination pathway. These findings, including a similar role of ACS-4 in a male/female species, uncover a likely conserved mechanism by which FA, an environmental factor, regulates sex determination and reproductive development.

A recurrent missense variant in the E3 ubiquitin ligase substrate recognition subunit FEM1B causes a rare syndromic neurodevelopmental disorder.

PURPOSE: Fem1 homolog B (FEM1B) acts as a substrate recognition subunit for ubiquitin ligase complexes belonging to the CULLIN 2-based E3 family. Several biological functions have been proposed for FEM1B, including a structurally resolved function as a sensor for redox cell status by controlling mitochondrial activity, but its implication in human disease remains elusive. METHODS: To understand the involvement of FEM1B in human disease, we made use of Matchmaker exchange platforms to identify individuals with de novo variants in FEM1B and performed their clinical evaluation. We performed functional validation using primary neuronal cultures and in utero electroporation assays, as well as experiments on patient's cells. RESULTS: Five individuals with a recurrent de novo missense variant in FEM1B were identified: NM_015322.5:c.377G>A NP_056137.1:p.(Arg126Gln) (FEM1BR126Q). Affected individuals shared a severe neurodevelopmental disorder with behavioral phenotypes and a variable set of malformations, including brain anomalies, clubfeet, skeletal abnormalities, and facial dysmorphism. Overexpression of the FEM1BR126Q variant but not FEM1B wild-type protein, during mouse brain development, resulted in delayed neuronal migration of the target cells. In addition, the individuals' cells exhibited signs of oxidative stress and induction of type I interferon signaling. CONCLUSION: Overall, our data indicate that p.(Arg126Gln) induces aberrant FEM1B activation, resulting in a gain-of-function mechanism associated with a severe syndromic developmental disorder in humans.

Modelling spatio-temporal interactions between second messengers Ca 2 + and cAMP in a pancreatic ß -cell.

Calcium serves as a widespread second messenger in almost every human and animal cell. The regulation of various cellular processes, such as transcriptional control and the kinetics of membrane channels, is significantly influenced by intracellular calcium ions (Ca 2 + ), and linkages between Ca 2 + and other second messengers should activate signaling networks. The passage of ions across the cell membrane regulates Ca 2 + levels in pancreatic ß -cells and requires the coordinated interaction of various ion transport mechanisms and organelles. The signaling of Ca 2 + in ß -cells and its interactions with the intracellular dynamics of cyclic adenosine monophosphate (cAMP) is poorly understood. Therefore, the current investigation proposes a mathematical model to illustrate the spatiotemporal dynamical interaction between Ca 2 + and cAMP. In order to construct a one-dimensional mathematical model, the fundamental initial and boundary conditions derived from the physiological characteristics of the ß -cell are incorporated. The numerical results were obtained by MATLAB simulations using the finite element method and the Crank-Nicolson method. The current study aims to offer an update on regulation between Ca 2 + and cAMP signaling circuits, with a focus on interactions that occur in localized areas of the ß -cell. The model gives the individual effect of each parameter on the regulation of Ca 2 + and cAMP profiles in a ß -cell. Evidently, impairments in the regulation of messenger pathways contribute to the pathological conditions, as demonstrated by the results obtained.

Hidden functional complexity in the flora of an early land ecosystem.

The first land ecosystems were composed of organisms considered simple in nature, yet the morphological diversity of their flora was extraordinary. The biological significance of this diversity remains a mystery largely due to the absence of feasible study approaches. To study the functional biology of Early Devonian flora, we have reconstructed extinct plants from fossilised remains in silico. We explored the morphological diversity of sporangia in relation to their mechanical properties using finite element method. Our approach highlights the impact of sporangia morphology on spore dispersal and adaptation. We discovered previously unidentified innovations among early land plants, discussing how different species might have opted for different spore dispersal strategies. We present examples of convergent evolution for turgor pressure resistance, achieved by homogenisation of stress in spherical sporangia and by torquing force in Tortilicaulis-like specimens. In addition, we show a potential mechanism for stress-assisted sporangium rupture. Our study reveals the deceptive complexity of this seemingly simple group of organisms. We leveraged the quantitative nature of our approach and constructed a fitness landscape to understand the different ecological niches present in the Early Devonian Welsh Borderland flora. By connecting morphology to functional biology, these findings facilitate a deeper understanding of the diversity of early land plants and their place within their ecosystem.

W chromosome sequences of two bombycid moths provide an insight into the origin of Fem.

Fem is a W-linked gene that encodes a piRNA precursor, and its product, Fem piRNA, is a master factor of female determination in Bombyx mori. Fem has low similarity to any known sequences, and the origin of Fem remains unclear. So far, two hypotheses have been proposed for the origin of Fem: The first hypothesis is that Fem is an allele of Masc, which assumes that the W chromosome was originally a homologous chromosome of the Z chromosome. The second hypothesis is that Fem arose by the transposition of Masc to the W chromosome. To explore the origin of Fem, we determined the W chromosome sequences of B. mori and, as a comparison, a closely relative bombycid species of Trilocha varians with a Fem-independent sex determination system. To our surprise, although the sequences of W and Z chromosomes show no homology to each other, a few pairs of homologues are shared by W and Z chromosomes, indicating the W chromosome of both species originated from Z chromosome. In addition, the W chromosome of T. varians lacks Fem, while the W chromosome of B. mori has over 100 copies of Fem. The high-quality assembly of the W chromosome of B. mori arose the third hypothesis about the origin of Fem: Fem is a chimeric sequence of multiple transposons. More than half of one transcriptional unit of Fem shows a significant homology to RTE-BovB. Moreover, the Fem piRNA-producing region could correspond to the boundary of the two transposons, gypsy and satellite DNA.

Simulative investigation of the required level of geometrical individualization of the lumbar spines to predict fractures.

Injury mechanisms of the lumbar spine under dynamic loading are dependent on spine curvature and anatomical variation. Impact simulation with finite element (FE) models can assist the reconstruction and prediction of injuries. The objective of this study was to determine which level of individualization of a baseline FE lumbar spine model is necessary to replicate experimental responses and fracture locations in a dynamic experiment.Experimental X-rays from 26 dynamic drop tower tests were used to create three configurations of a lumbar spine model (T12 to L5): baseline, with aligned vertebrae (positioned), and with aligned and morphed vertebrae (morphed). Each model was simulated with the corresponding loading and boundary conditions from dynamic lumbar spine experiments. Force, moment, and kinematic responses were compared to the experimental data. Cosine similarity was computed to assess how well simulation responses match the experimental data. The pressure distribution within the vertebrae was used to compare fracture risk and fracture location between the different models.The positioned models replicated the injured spinal level and the fracture patterns quite well, though the morphed models provided slightly more accuracy. However, for impact reconstruction or injury prediction, the authors recommend pure positioning for whole-body models, as the gain in accuracy was relatively small, while the morphing modifications of the model require considerably higher efforts. These results improve the understanding of the application of human body models to investigate lumbar injury mechanisms with FE models.

Turing pattern formation on the sphere is robust to the removal of a hole.

The formation of buds on the cell membrane of budding yeast cells is thought to be driven by reactions and diffusion involving the protein Cdc42. These processes can be described by a coupled system of partial differential equations known as the Schnakenberg system. The Schnakenberg system is known to exhibit diffusion-driven pattern formation, thus providing a mechanism for bud formation. However, it is not known how the accumulation of bud scars on the cell membrane affect the ability of the Schnakenberg system to form patterns. We have approached this problem by modelling a bud scar on the cell membrane with a hole on the sphere. We have studied how the spectrum of the Laplace-Beltrami operator, which determines the resulting pattern, is affected by the size of the hole, and by numerically solving the Schnakenberg system on a sphere with a hole using the finite element method. Both theoretical predictions and numerical solutions show that pattern formation is robust to the introduction of a bud scar of considerable size, which lends credence to the hypothesis that bud formation is driven by diffusion-driven instability.

Numerical model of pressure generated by elastic compression garments on a compressible human limb analogue.

OBJECTIVE: This study aimed to formulate a numerical approach (finite element modelling (FEM)) to calculate pressure values generated by compression garments on a compressible limb analogue, and to validate the numerical approach using experimental measurements. Existing models were also compared. METHOD: Experimentally measured pressure values and deformation caused by compression bands on a compressible human limb analogue were compared with values predicted using the Young-Laplace equation, a previously formulated analytical model and the FEM. RESULTS: The FEM provided greater accuracy in predicting the pressure generated by compression bands compared to existing models. The FEM also predicted deformation of the limb analogue with good agreement relative to experimental values. CONCLUSION: It was concluded that modelling the non-uniform manner in which the way a limb analogue is compressed should be incorporated into future modelling of the pressures generated by compression garments on a compressible limb analogue. DECLARATION OF INTEREST: The authors have no conflicts of interest to declare.

Model of Calcium Dynamics Regulating [Formula: see text], ATP and Insulin Production in a Pancreatic [Formula: see text]-Cell.

The calcium signals regulate the production and secretion of many signaling molecules like inositol trisphosphate ([Formula: see text]) and adenosine triphosphate (ATP) in various cells including pancreatic [Formula: see text]-cells. The calcium signaling mechanisms regulating [Formula: see text], ATP and insulin responsible for various functions of [Formula: see text]-cells are still not well understood. Any disturbance in these mechanisms can alter the functions of [Formula: see text]-cells leading to diabetes and metabolic disorders. Therefore, a mathematical model is proposed by incorporating the reaction-diffusion equation for calcium dynamics and a system of first-order differential equations for [Formula: see text], ATP-production and insulin secretion with initial and boundary conditions. The model incorporates the temporal dependence of [Formula: see text]-production and degradation, ATP production and insulin secretion on calcium dynamics in a [Formula: see text]-cell. The piecewise linear finite element method has been used for the spatial dimension and the Crank-Nicolson scheme for the temporal dimension to obtain numerical results. The effect of changes in source influxes and buffers on calcium dynamics and production of [Formula: see text], ATP and insulin levels in a [Formula: see text]-cell has been analyzed. It is concluded that the dysfunction of source influx and buffers can cause significant variations in calcium levels and dysregulation of [Formula: see text], ATP and insulin production, which can lead to various metabolic disorders, diabetes, obesity, etc. The proposed model provides crucial information about the changes in mechanisms of calcium dynamics causing proportionate disturbances in [Formula: see text], ATP and insulin levels in pancreatic cells, which can be helpful for devising protocols for diagnosis and treatment of various metabolic diseases.

A Self-Temperature Compensation Barometer Based on All-Quartz Resonant Pressure Sensor.

This paper reports a self-temperature compensation barometer based on a quartz resonant pressure sensor. A novel sensor chip that contains a double-ended tuning fork (DETF) resonator and a single-ended tuning fork (SETF) resonator is designed and fabricated. The two resonators are designed on the same diaphragm. The DETF resonator works as a pressure sensor. To reduce the influence of the temperature drift, the SETF resonator works as a temperature compensation sensor, which senses the instantaneous temperature of the DETF resonator. The temperature compensation method based on polynomial fitting is studied. The experimental results show that the accuracy is 0.019% F.S. in a pressure range of 200~1200 hPa over a temperature range of -20 °C~+60 °C. The absolute errors of the barometer are within ±23 Pa. To verify its actual performance, a drone flight test was conducted. The test results are consistent with the actual flight trajectory.

Detection of a Submillimeter Notch-Type Defect at Multiple Orientations by a Lamb Wave A0 Mode at 550 kHz for Long-Range Structural Health Monitoring Applications.

The early detection of small cracks in large metal structures is a crucial requirement for the implementation of a structural health monitoring (SHM) system with a low transducers density. This work tackles the challenging problem of the early detection of submillimeter notch-type defects with a semielliptical shape and a groove at a constant width of 100 µm and 3 mm depth in a 4.1 mm thick aluminum plate. This defect is investigated with an ultrasonic guided wave (UGW) A0 mode at 550 kHz to investigate the long range in thick metal plates. The mode selection is obtained by interdigital transducers (IDTs) designed to operate with a 5 mm central wavelength. The novel contribution is the validation of the detection by pulse-echo and pitch and catch with UGW transducers to cover a distance up to 70 cm to reduce the transducers density. The analysis of scattering from this submillimeter defect at different orientations is carried out using simulations with a Finite Element Model (FEM). The detection of the defect is obtained by comparing the scattered signals from the defect with baseline signals of the pristine laminate. Finally, the paper shows that the simulated results are in good agreement with the experimental ones, demonstrating the possible implementation in an SHM system based on the efficient propagation of an antisymmetric mode by IDTs.

A Combined Magnetoelectric Sensor Array and MRI-Based Human Head Model for Biomagnetic FEM Simulation and Sensor Crosstalk Analysis.

Magnetoelectric (ME) magnetic field sensors are novel sensing devices of great interest in the field of biomagnetic measurements. We investigate the influence of magnetic crosstalk and the linearity of the response of ME sensors in different array and excitation configurations. To achieve this aim, we introduce a combined multiscale 3D finite-element method (FEM) model consisting of an array of 15 ME sensors and an MRI-based human head model with three approximated compartments of biological tissues for skin, skull, and white matter. A linearized material model at the small-signal working point is assumed. We apply homogeneous magnetic fields and perform inhomogeneous magnetic field excitation for the ME sensors by placing an electric point dipole source inside the head. Our findings indicate significant magnetic crosstalk between adjacent sensors leading down to a 15.6% lower magnetic response at a close distance of 5 mm and an increasing sensor response with diminishing crosstalk effects at increasing distances up to 5 cm. The outermost sensors in the array exhibit significantly less crosstalk than the sensors located in the center of the array, and the vertically adjacent sensors exhibit a stronger crosstalk effect than the horizontally adjacent ones. Furthermore, we calculate the ratio between the electric and magnetic sensor responses as the sensitivity value and find near-constant sensitivities for each sensor, confirming a linear relationship despite magnetic crosstalk and the potential to simulate excitation sources and sensor responses independently.

A Dual-Mode Surface Acoustic Wave Delay Line for the Detection of Ice on 64°-Rotated Y-Cut Lithium Niobate.

Ice accumulation on infrastructure poses severe safety risks and economic losses, necessitating effective detection and monitoring solutions. This study introduces a novel approach employing surface acoustic wave (SAW) sensors, known for their small size, wireless operation, energy self-sufficiency, and retrofit capability. Utilizing a SAW dual-mode delay line device on a 64°-rotated Y-cut lithium niobate substrate, we demonstrate a solution for combined ice detection and temperature measurement. In addition to the shear-horizontal polarized leaky SAW, our findings reveal an electrically excitable Rayleigh-type wave in the X+90° direction on the same cut. Experimental results in a temperature chamber confirm capability for reliable differentiation between liquid water and ice loading and simultaneous temperature measurements. This research presents a promising advancement in addressing safety concerns and economic losses associated with ice accretion.

Regulatory disturbances in the dynamical signaling systems of C a 2 + and NO in fibroblasts cause fibrotic disorders.

Studying the calcium dynamics within a fibroblast cell individually has provided only a restricted understanding of its functions. However, research efforts focusing on systems biology approaches for such investigations have been largely neglected by researchers until now. Fibroblast cells rely on signaling from calcium ( C a 2 + ) and nitric oxide (NO) to maintain their physiological functions and structural stability. Various studies have demonstrated the correlation between NO and the control of C a 2 + dynamics in cells. However, there is currently no existing model to assess the disruptions caused by various factors in regulatory dynamics, potentially resulting in diverse fibrotic disorders. A mathematical model has been developed to investigate the effects of changes in parameters such as buffer, receptor, sarcoplasmic endoplasmic reticulum C a 2 + -ATPase (SERCA) pump, and source influx on the regulation and dysregulation of spatiotemporal calcium and NO dynamics in fibroblast cells. This model is based on a system of reaction-diffusion equations, and numerical simulations are conducted using the finite element method. Disturbances in key processes related to calcium and nitric oxide, including source influx, buffer mechanism, SERCA pump, and inositol trisphosphate ( I P 3 ) receptor, may contribute to deregulation in the calcium and NO dynamics within fibroblasts. The findings also provide new insights into the extent and severity of disorders resulting from alterations in various parameters, potentially leading to deregulation and the development of fibrotic disease.

Effects of different patterns of movement for correcting a deep curve of Spee with clear aligners on the anterior teeth: a finite element analysis.

OBJECTIVE: To analyse the anterior teeth effects of clear aligners on five different patterns of mandibular molar movement and to define the most effective configuration to be implemented with clear aligners through finite element analysis. METHODS: A three-dimensional mandibular model with a deep overbite in the mandible was constructed using cone beam computerized tomography (CBCT) data. The model included the mandibular dentition, mandibular periodontal ligaments, attachments, and aligners. Five models were created: (1) configuration A: second molar distalization (0.25 mm); (2) configuration B: second molar distalization (0.25 mm), first molar extrusion (0.15 mm); (3) configuration C: second molar distalization (0.25 mmm), first and second premolar extrusion(0.15 mm); (4) configuration D: second molar distalization (0.25 mm), first molar and first/second premolar extrusion(0.15 mm); and (5) configuration E: second molar distalization (0.25 mm), first molar and first/second premolar extrusion (0.15 mm), first molar and first/second premolar expansion (0.15 mm). RESULTS: In all configurations, the anterior teeth exhibited labial tipping and the mandibular central incisor of configuration E showed the highest labial tipping. Configuration E demonstrated a relatively minor impact on mandibular molars distalization compared with configuration A. Configuration A showed the highest distal displacement value, and configuration E produced the lowest displacement value. Configuration E caused the highest periodontal ligament (PDL) pressure of the central and lateral incisors. The differences in the canines between configurations C and D,were not significant, and the stress distribution differed among the five groups. CONCLUSIONS: All patterns utilizing clear aligners facilitated mandibular molar distalization. Extruding the premolars and second molar distalization at the same time had little impact on second molar distalization; When expansion and extrusion were simultaneously performed during the distalization of mandibular molars, our prime consideration was the alveolar bone on the labial side of the anterior teeth to prevent the occurrence of gingival recession, dehiscence, and fenestration. Due to the lack of consideration for periodontal tissues in this study, clinical protocols should be designed based on the periodontal status of the mandibular anterior teeth.

Automatic quality control of the numerical accuracy of EEG lead fields.

Precise individualized EEG source localization is predicated on having accurate subject-specific Lead Fields (LFs) obtained from their Magnetic Resonance Images (MRI). LF calculation is a complex process involving several error-prone steps that start with obtaining a realistic head model from the MRI and finalizing with computationally expensive solvers such as the Boundary Element Method (BEM) or Finite Element Method (FEM). Current Big-Data applications require the calculation of batches of hundreds or thousands of LFs. LF. Quality Control is conventionally checked subjectively by experts, a procedure not feasible in practice for larger batches. To facilitate this step, we introduce the Lead Field Automatic-Quality Control Index (LF-AQI) that flags LF with potential errors. We base our LF-AQI on the assumption that LFs obtained from simpler head models, i.e., the homogeneous head model LF (HHM-LF) or spherical head model LF (SHM-LF), deviate only moderately from a "good" realistic test LF. Since these simpler LFs are easier to compute and check for errors, they may serve as "reference LF" to detect anomalous realistic test LF. We investigated this assumption by comparing correlation-based channel ρmin(ref,test)and source τmin(ref,test) similarity indices (SI) between "gold standards," i.e., very accurate FEM and BEM LFs, and the proposed references (HHM-LF and SHM-LF). Surprisingly we found that the most uncomplicated possible reference, HHM-LF had high SI values with the gold standards-leading us to explore further use of the channel ρmin(HHM-LF,test)and source τmin(HHM-LF,test)SI as a basis for our LF-AQI. Indeed, these SI successfully detected five simulated scenarios of LFs artifacts. This result encouraged us to evaluate the SI on a large dataset and thus define our LF-AQI. We thus computed the SI of 1251 LFs obtained from the Child Mind Institute (CMI) MRI dataset. When ρmin(HHM-LF,test)and source τmin(HHM-LF,test) were plotted for all test subjects on a 2D space, most were tightly clustered around the median of a high similarity centroid (HSC), except for a smaller proportion of outliers. We define the LF-AQI for a given LF as the log Euclidean distance between its SI and the HSC median. To automatically detect outliers, the threshold is at the 90th percentile of the CMI LF-AQIs (-0.9755). LF-AQI greater than this threshold flag individual LF to be checked. The robustness of this LF-AQI screening was checked by repeated out-of-sample validation. Strikingly, minor corrections in re-processing the flagged cases eliminated their status as outliers. Furthermore, the "doubtful" labels assigned by LF-AQI were validated by neuroscience students using a Likert scale questionnaire designed to manually check the LF's quality. Item Response Theory (IRT) analysis was applied to the questionnaire results to compute an optimized model and a latent variable θ for that model. A linear mixed model (LMM) between the θ and LF-AQI resulted in an effect with a Cohen's d value of 1.3 and a p-value <0.001, thus validating the correspondence of LF-AQI with the visual quality control. We provide an open-source pipeline to implement both LF calculation and its quality control to allow further evaluation of our index.

Outcome measures for electric field modeling in tES and TMS: A systematic review and large-scale modeling study.

BACKGROUND: Electric field (E-field) modeling is a potent tool to estimate the amount of transcranial magnetic and electrical stimulation (TMS and tES, respectively) that reaches the cortex and to address the variable behavioral effects observed in the field. However, outcome measures used to quantify E-fields vary considerably and a thorough comparison is missing. OBJECTIVES: This two-part study aimed to examine the different outcome measures used to report on tES and TMS induced E-fields, including volume- and surface-level gray matter, region of interest (ROI), whole brain, geometrical, structural, and percentile-based approaches. The study aimed to guide future research in informed selection of appropriate outcome measures. METHODS: Three electronic databases were searched for tES and/or TMS studies quantifying E-fields. The identified outcome measures were compared across volume- and surface-level E-field data in ten tES and TMS modalities targeting two common targets in 100 healthy individuals. RESULTS: In the systematic review, we extracted 308 outcome measures from 202 studies that adopted either a gray matter volume-level (n = 197) or surface-level (n = 111) approach. Volume-level results focused on E-field magnitude, while surface-level data encompassed E-field magnitude (n = 64) and normal/tangential E-field components (n = 47). E-fields were extracted in ROIs, such as brain structures and shapes (spheres, hexahedra and cylinders), or the whole brain. Percentiles or mean values were mostly used to quantify E-fields. Our modeling study, which involved 1,000 E-field models and > 1,000,000 extracted E-field values, revealed that different outcome measures yielded distinct E-field values, analyzed different brain regions, and did not always exhibit strong correlations in the same within-subject E-field model. CONCLUSIONS: Outcome measure selection significantly impacts the locations and intensities of extracted E-field data in both tES and TMS E-field models. The suitability of different outcome measures depends on the target region, TMS/tES modality, individual anatomy, the analyzed E-field component and the research question. To enhance the quality, rigor, and reproducibility in the E-field modeling domain, we suggest standard reporting practices across studies and provide four recommendations.

Disturbances in system dynamics of [Formula: see text] and [Formula: see text] perturbing insulin secretion in a pancreatic [Formula: see text]-cell due to type-2 diabetes.

The individual study of [Formula: see text] and [Formula: see text] dynamics respectively in a [Formula: see text]-cell has yielded limited information about the cell functions. But the systems biology approaches for such studies have received very little attention by the research workers in the past. In the present work, a system-dynamics model for the interdependent [Formula: see text] and [Formula: see text] signaling that controls insulin secretion in a [Formula: see text]-cell has been suggested. A two-way feedback system of [Formula: see text] and [Formula: see text] has been considered and one-way feedback between [Formula: see text] and insulin has been implemented in the model. The finite element method along with the Crank-Nicolson method have been applied for simulation. Numerical results have been used to analyze the impact of perturbations in [Formula: see text] and [Formula: see text] dynamics on insulin secretion for normal and Type-2 diabetic conditions. The results reveal that Type-2 diabetes comes from abnormalities in insulin secretion caused by the perturbation in buffers and pumps (SERCA and PMCA).