Ecophysiological Crop Modelling Combined with Genetic Analysis Is a Powerful Tool for Ideotype Design

Improving the grain yield of crops in both favourable and stressful environments is the main breeding objective required to ensure food security. In this review, I outline a genotype-to-phenotype approach that exploits the potential values of quantitative genetics and process-based crop modelling in developing new plant types with high yields. The effects of quantitative trait locus (QTL), for traits typically at the single-organ level over a short time scale, were projected for their impact on crop growth during the whole growing season in the field. This approach can provide more markers for selection programmes for specific environments whilst also allowing for prioritization. Crop modelling is thus a powerful tool for ideotyping under contrasting conditions, i.e., use of single-environment information for predicting phenotypes under different environments.

Microstructural Dynamics of the Myocardium: Orientation of the Muscle Fibers and Occurrence of Cardiomyopathies

This paper considers the Holzapfel–Ogden (HO) model to examine the behavior of the left ventricle myocardium. At the tissue level, we analyze the contributions of the orientation angle of muscle fibers (MFs) and investigate their effects on the occurrence of certain cardiomyopathies and congenital diseases at the organ level. Knowing the importance of myocardial microstructure on cardiac function, we vary the angle between the direction of collagen sheets and MFs in all layers of the myocardium (from epicardium to endocardium) to model the effects of tilted MFs. Based on the HO model in which the directions of the fibers are orthogonal and using the strain energy of HO, we construct a tensile-compression test and simulate the dynamics of a cubic sample. We recover the authors’ results exhibiting the existence of residual stresses in various directions. Then, we modify the energy of HO slightly to assess the impact of the same stress states on the system with tilted MFs. A numerical tensile-compression test performed on this new cubic sample shows that, in certain directions, the heart tissue is more resistant to shear deformations in some planes than in others. Moreover, it appears that the residual stress is smaller as the angle of orientation of the MFs is small. Furthermore, we observe that the residual stress is greater in the new model compared to the normal HO model. This could affect the heart muscle at the organ level leading to hypertrophied/dilated cardiomyopathy.

Young and Aged Neuronal Tissue Dynamics With a Simplified Neuronal Patch Cellular Automata Model

Realistic single-cell neuronal dynamics are typically obtained by solving models that involve solving a set of differential equations similar to the Hodgkin-Huxley (HH) system. However, realistic simulations of neuronal tissue dynamics —especially at the organ level, the brain— can become intractable due to an explosion in the number of equations to be solved simultaneously. Consequently, such efforts of modeling tissue- or organ-level systems require a lot of computational time and the need for large computational resources. Here, we propose to utilize a cellular automata (CA) model as an efficient way of modeling a large number of neurons reducing both the computational time and memory requirement. First, a first-order approximation of the response function of each HH neuron is obtained and used as the response-curve automaton rule. We then considered a system where an external input is in a few cells. We utilize a Moore neighborhood (both totalistic and outer-totalistic rules) for the CA system used. The resulting steady-state dynamics of a two-dimensional (2D) neuronal patch of size 1, 024 × 1, 024 cells can be classified into three classes: (1) Class 0–inactive, (2) Class 1–spiking, and (3) Class 2–oscillatory. We also present results for different quasi-3D configurations starting from the 2D lattice and show that this classification is robust. The numerical modeling approach can find applications in the analysis of neuronal dynamics in mesoscopic scales in the brain (patch or regional). The method is applied to compare the dynamical properties of the young and aged population of neurons. The resulting dynamics of the aged population shows higher average steady-state activity 〈a(t → ∞)〉 than the younger population. The average steady-state activity 〈a(t → ∞)〉 is significantly simplified when the aged population is subjected to external input. The result conforms to the empirical data with aged neurons exhibiting higher firing rates as well as the presence of firing activity for aged neurons stimulated with lower external current.

CHIQUITA1 maintains temporal transition between proliferation and differentiation in Arabidopsis thaliana

Body size varies widely among species, populations, and individuals depending on the environment. Transitioning between proliferation and differentiation is a crucial determinant of final organ size, but how the timing of this transition is established and maintained remains unknown. Using cell proliferation markers and genetic analysis, we show that CHIQUITA1 (CHIQ1) is required to maintain the timing of the transition from proliferation to differentiation in Arabidopsis thaliana. Combining kinematic and cell lineage tracking studies, we found that the number of actively dividing cells in chiquita1-1 plants decreases prematurely compared to wild type plants, suggesting CHIQ1 maintains the proliferative capacity in dividing cells and ensures that cells divide a certain number of times. CHIQ1 belongs to a plant-specific gene family of unknown molecular function and physically and genetically interacts with three close members of its family to control the timing of proliferation exit. Our work reveals the interdependency between cellular and organ-level processes underlying final organ size determination.

Virtual reality for 3D histology: multi-scale visualization of organs with interactive feature exploration

Background Virtual reality (VR) enables data visualization in an immersive and engaging manner, and it can be used for creating ways to explore scientific data. Here, we use VR for visualization of 3D histology data, creating a novel interface for digital pathology to aid cancer research. Methods Our contribution includes 3D modeling of a whole organ and embedded objects of interest, fusing the models with associated quantitative features and full resolution serial section patches, and implementing the virtual reality application. Our VR application is multi-scale in nature, covering two object levels representing different ranges of detail, namely organ level and sub-organ level. In addition, the application includes several data layers, including the measured histology image layer and multiple representations of quantitative features computed from the histology. Results In our interactive VR application, the user can set visualization properties, select different samples and features, and interact with various objects, which is not possible in the traditional 2D-image view used in digital pathology. In this work, we used whole mouse prostates (organ level) with prostate cancer tumors (sub-organ objects of interest) as example cases, and included quantitative histological features relevant for tumor biology in the VR model. Conclusions Our application enables a novel way for exploration of high-resolution, multidimensional data for biomedical research purposes, and can also be used in teaching and researcher training. Due to automated processing of the histology data, our application can be easily adopted to visualize other organs and pathologies from various origins.

Multiomic study of skin, peripheral blood, and serum: is serum proteome a reflection of disease process at the end-organ level in systemic sclerosis?

Background Serum proteins can be readily assessed during routine clinical care. However, it is unclear to what extent serum proteins reflect the molecular dysregulations of peripheral blood cells (PBCs) or affected end-organs in systemic sclerosis (SSc). We conducted a multiomic comparative analysis of SSc serum profile, PBC, and skin gene expression in concurrently collected samples. Methods Global gene expression profiling was carried out in skin and PBC samples obtained from 49 SSc patients enrolled in the GENISOS observational cohort and 25 unaffected controls. Levels of 911 proteins were determined by Olink Proximity Extension Assay in concurrently collected serum samples. Results Both SSc PBC and skin transcriptomes showed a prominent type I interferon signature. The examination of SSc serum profile revealed an upregulation of proteins involved in pro-fibrotic homing and extravasation, as well as extracellular matrix components/modulators. Notably, several soluble receptor proteins such as EGFR, ERBB2, ERBB3, VEGFR2, TGFBR3, and PDGF-Rα were downregulated. Thirty-nine proteins correlated with severity of SSc skin disease. The differential expression of serum protein in SSc vs. control comparison significantly correlated with the differential expression of corresponding transcripts in skin but not in PBCs. Moreover, the differentially expressed serum proteins were significantly more connected to the Well-Associated-Proteins in the skin than PBC gene expression dataset. The assessment of the concordance of between-sample similarities revealed that the molecular profile of serum proteins and skin gene expression data were significantly concordant in patients with SSc but not in healthy controls. Conclusions SSc serum protein profile shows an upregulation of profibrotic cytokines and a downregulation of soluble EGF and other key receptors. Our multilevel comparative analysis indicates that the serum protein profile in SSc correlates more closely with molecular dysregulations of skin than PBCs and might serve as a reflection of disease severity at the end-organ level.

Physiological responses of freshwater insects to salinity: molecular-, cellular- and organ-level studies

ABSTRACT Salinization of freshwater is occurring throughout the world, affecting freshwater biota that inhabit rivers, streams, ponds, marshes and lakes. There are many freshwater insects, and these animals are important for ecosystem health. These insects have evolved physiological mechanisms to maintain their internal salt and water balance based on a freshwater environment that has comparatively little salt. In these habitats, insects must counter the loss of salts and dilution of their internal body fluids by sequestering salts and excreting water. Most of these insects can tolerate salinization of their habitats to a certain level; however, when exposed to salinization they often exhibit markers of stress and impaired development. An understanding of the physiological mechanisms for controlling salt and water balance in freshwater insects, and how these are affected by salinization, is needed to predict the consequences of salinization for freshwater ecosystems. Recent research in this area has addressed the whole-organism response, but the purpose of this Review is to summarize the effects of salinization on the osmoregulatory physiology of freshwater insects at the molecular to organ level. Research of this type is limited, and pursuing such lines of inquiry will improve our understanding of the effects of salinization on freshwater insects and the ecosystems they inhabit.

A Reversal in Hair Cell Orientation Organizes Both the Auditory and Vestibular Organs

Sensory hair cells detect mechanical stimuli with their hair bundle, an asymmetrical brush of actin-based membrane protrusions, or stereocilia. At the single cell level, stereocilia are organized in rows of graded heights that confer the hair bundle with intrinsic directional sensitivity. At the organ level, each hair cell is precisely oriented so that its intrinsic directional sensitivity matches the direction of mechanical stimuli reaching the sensory epithelium. Coordinated orientation among neighboring hair cells usually ensures the delivery of a coherent local group response. Accordingly, hair cell orientation is locally uniform in the auditory and vestibular cristae epithelia in birds and mammals. However, an exception to this rule is found in the vestibular macular organs, and in fish lateral line neuromasts, where two hair cell populations show opposing orientations. This mirror-image hair cell organization confers bidirectional sensitivity at the organ level. Here I review our current understanding of the molecular machinery that produces mirror-image organization through a regional reversal of hair cell orientation. Interestingly, recent evidence suggests that auditory hair cells adopt their normal uniform orientation through a global reversal mechanism similar to the one at work regionally in macular and neuromast organs. Macular and auditory organs thus appear to be patterned more similarly than previously appreciated during inner ear development.