Free volume theory explains the unusual behavior of viscosity in a non-confluent tissue during morphogenesis.

A recent experiment on zebrafish blastoderm morphogenesis showed that the viscosity (η) of a non-confluent embryonic tissue grows sharply until a critical cell packing fraction (ϕS). The increase in η up to ϕS is similar to the behavior observed in several glass-forming materials, which suggests that the cell dynamics is sluggish or glass-like. Surprisingly, η is a constant above ϕS. To determine the mechanism of this unusual dependence of η on ϕ, we performed extensive simulations using an agent-based model of a dense non-confluent two-dimensional tissue. We show that polydispersity in the cell size, and the propensity of the cells to deform, results in the saturation of the available free area per cell beyond a critical packing fraction. Saturation in the free space not only explains the viscosity plateau above ϕS but also provides a relationship between equilibrium geometrical packing to the dramatic increase in the relaxation dynamics.

3D Hydrogel Encapsulation Regulates Nephrogenesis in Kidney Organoids.

Stem cell-derived kidney organoids contain nephron segments that recapitulate morphological and functional aspects of the human kidney. However, directed differentiation protocols for kidney organoids are largely conducted using biochemical signals to control differentiation. Here, the hypothesis that mechanical signals regulate nephrogenesis is investigated in 3D culture by encapsulating kidney organoids within viscoelastic alginate hydrogels with varying rates of stress relaxation. Tubular nephron segments are significantly more convoluted in kidney organoids differentiated in encapsulating hydrogels when compared with those in suspension culture. Hydrogel viscoelasticity regulates the spatial distribution of nephron segments within the differentiating kidney organoids. Consistent with these observations, a particle-based computational model predicts that the extent of deformation of the hydrogel-organoid interface regulates the morphology of nephron segments. Elevated extracellular calcium levels in the culture medium, which can be impacted by the hydrogels, decrease the glomerulus-to-tubule ratio of nephron segments. These findings reveal that hydrogel encapsulation regulates nephron patterning and morphology and suggest that the mechanical microenvironment is an important design variable for kidney regenerative medicine.

The Flower Colour Influences Spontaneous Nectaring in Butterflies: a Case Study with Twenty Subtropical Butterflies.

Butterflies have a wide spectrum of colour vision, and changes in flower colour influence both the visiting and nectaring (the act of feeding on flower nectar) events of them. However, the spontaneous behavioural response of butterflies while foraging on real flowers is less characterised in wild conditions. Hence, this study intends to investigate flower colour affinity in wild butterflies in relation to nectaring frequency (NF) and nectaring duration (ND). Six distinct flower colours were used to study spontaneous nectaring behaviour in 20 species of subtropical butterflies. Both NF and ND greatly varied in the flower colours they offered. Yellow flowers were frequently imbibed by butterflies for longer durations, followed by orange, while red, pink, white and violet flowers were occasionally nectared in shorter bouts. Though butterflies have a general tendency to nectar on multiple flower colours, the Nymphalids were more biased towards nectaring on yellow flowers, but Papilionids preferred both yellow and orange, while the Pierids were likely to display an equal affinity for yellow, orange and violet flowers as their first order of preference. Even if the blooms are associated with higher nectar concentrations or a significant grade reward, the butterfly may prefer to visit different-coloured flowers instead. Flower colour choice appears to be a generalist phenomenon for butterflies, but their specialist visiting nature was also significant. Nymphalid representatives responded to a wider variety of floral colour affinities than Pierid and Papilionid species. The colour preference of butterflies aids in the identification of flowers during foraging and influences subsequent foraging decisions, which ultimately benefits pollination success. The current information will support the preservation and conservation of butterflies in their natural habitats.

Observe without disturbing: tracer particles sense local stresses in cell collectives without affecting the cancer cell dynamics.

Measurements of local stresses on the cancer cells (CCs), inferred by embedding inert compressible tracer particles (TPs) in a growing multicellular spheroid (MCS), show that pressure decreases monotonically as the distance from the core of the MCS increases. How faithfully do the TPs report the local stresses in the CCs is an important question because pressure buildup in the MCS is dynamically generated due to CC division, which implies that the CC dynamics should be minimally altered by the TPs. Here using theory and simulations, we show that although the TP dynamics is unusual, exhibiting sub-diffusive behavior on times less than the CC division times and hyper-diffusive dynamics in the long-time limit, they do not affect the long-time CC dynamics. The CC pressure profile within the MCS, which decays from a high value at the core to the periphery, is almost identical with and without the TPs. That the TPs have a small effect on the local stresses in the MCS implies that they are reasonale reporters of the CC microenvironment.

Determining Complete Chromosomal Haplotypes by mLinker.

Haplotype ("haploid genotype") phase is the combination of genotypes at sites of genetic variation along a chromosome [1]. We previously demonstrated that the complete chromosomal haplotype of diploid human genomes can be determined using molecular linkage from Hi-C sequencing and linked-reads sequencing [2]. In this chapter, we present a step-by-step guide to perform this analysis using mLinker, a software package for haplotype inference.

Mechanical feedback controls the emergence of dynamical memory in growing tissue monolayers.

The growth of a tissue, which depends on cell-cell interactions and biologically relevant processes such as cell division and apoptosis, is regulated by a mechanical feedback mechanism. We account for these effects in a minimal two-dimensional model in order to investigate the consequences of mechanical feedback, which is controlled by a critical pressure, pc. A cell can only grow and divide if its pressure, due to interaction with its neighbors, is less than pc. Because temperature is not a relevant variable, the cell dynamics is driven by self-generated active forces (SGAFs) that arise due to cell division. We show that even in the absence of intercellular interactions, cells undergo diffusive behavior. The SGAF-driven diffusion is indistinguishable from the well-known dynamics of a free Brownian particle at a fixed finite temperature. When intercellular interactions are taken into account, we find persistent temporal correlations in the force-force autocorrelation function (FAF) that extends over a timescale of several cell division times. The time-dependence of the FAF reveals memory effects, which increases as pc increases. The observed non-Markovian effects emerge due to the interplay of cell division and mechanical feedback and are inherently a non-equilibrium phenomenon.

Adhesion strength between cells regulate nonmonotonic growth by a biomechanical feedback mechanism.

We determine how intercellular interactions and mechanical pressure experienced by single cells regulate cell proliferation using a minimal computational model for three-dimensional multicellular spheroid (MCS) growth. We discover that emergent spatial variations in the cell division rate, depending on the location of the cells either at the core or periphery within the MCS, is regulated by intercellular adhesion strength (fad). Varying fad results in nonmonotonic proliferation of cells in the MCS. A biomechanical feedback mechanism coupling the fad and microenvironment-dependent pressure fluctuations relative to a threshold value (pc) determines the onset of a dormant phase, and explains the nonmonotonic proliferation response. Increasing fad from low values enhances cell proliferation because pressure on individual cells is smaller compared with pc. However, at high fad, cells readily become dormant and cannot rearrange effectively in spacetime, leading to arrested cell proliferation. Utilizing our theoretical predictions, we explain experimental data on the impact of adhesion strength on cell proliferation and find good agreement. Our work, which shows that proliferation is regulated by pressure-adhesion feedback mechanism, may be a general feature of multicellular growth.

Interparticle Adhesion Regulates the Surface Roughness of Growing Dense Three-Dimensional Active Particle Aggregates.

Activity and self-generated motion are fundamental features observed in many living and nonliving systems. Given that interparticle adhesive forces can regulate particle dynamics, we investigate how interparticle adhesion strength controls the boundary growth and roughness of active particle aggregates. Using particle based simulations incorporating both activity (birth, death, and growth) and systematic physical interactions (elasticity and adhesion), we establish that interparticle adhesion strength (fad) controls the surface roughness of a densely packed three-dimensional(3D) active particle aggregate expanding into a highly viscous medium. We discover that the surface roughness of a 3D active particle aggregate increases in proportion to the interparticle adhesion strength (fad) and show that asymmetry in the radial and transverse active particle mean-squared displacement (MSD) suppresses 3D surface roughness at lower adhesion strengths. By analyzing the statistical properties of particle displacements at the aggregate periphery, we determine that the 3D surface roughness is driven by the movement of active particle toward the core at high interparticle adhesion strengths. Our results elucidate the physics controlling the expansion of adhesive 3D active particle collectives into a highly viscous medium, with implications into understanding stochastic interface growth in active matter systems characterized by self-generation of particles.

Self-generated persistent random forces drive phase separation in growing tumors.

A single solid tumor, composed of nearly identical cells, exhibits heterogeneous dynamics. Dynamics of cells in the core is glass-like, whereas those in the periphery undergoes diffusive or super-diffusive behavior. Quantification of heterogeneity using the mean square displacement or the self-intermediate scattering function, which involves averaging over the cell population, hides the complexity of the collective movement. Using the t-distributed stochastic neighbor embedding (t-SNE), a popular unsupervised machine learning dimensionality reduction technique, we show that the phase space structure of an evolving colony of cells, driven by cell division and apoptosis, partitions into nearly disjoint sets composed principally of the core and periphery cells. The non-equilibrium phase separation is driven by the differences in the persistence of self-generated active forces induced by cell division. Extensive heterogeneity revealed by t-SNE paves the way toward understanding the origins of intratumor heterogeneity using experimental imaging data.

Modelling climate change impacts on maize yields under low nitrogen input conditions in sub-Saharan Africa.

Smallholder farmers in sub-Saharan Africa (SSA) currently grow rainfed maize with limited inputs including fertilizer. Climate change may exacerbate current production constraints. Crop models can help quantify the potential impact of climate change on maize yields, but a comprehensive multimodel assessment of simulation accuracy and uncertainty in these low-input systems is currently lacking. We evaluated the impact of varying [CO2 ], temperature and rainfall conditions on maize yield, for different nitrogen (N) inputs (0, 80, 160 kg N/ha) for five environments in SSA, including cool subhumid Ethiopia, cool semi-arid Rwanda, hot subhumid Ghana and hot semi-arid Mali and Benin using an ensemble of 25 maize models. Models were calibrated with measured grain yield, plant biomass, plant N, leaf area index, harvest index and in-season soil water content from 2-year experiments in each country to assess their ability to simulate observed yield. Simulated responses to climate change factors were explored and compared between models. Calibrated models reproduced measured grain yield variations well with average relative root mean square error of 26%, although uncertainty in model prediction was substantial (CV = 28%). Model ensembles gave greater accuracy than any model taken at random. Nitrogen fertilization controlled the response to variations in [CO2 ], temperature and rainfall. Without N fertilizer input, maize (a) benefited less from an increase in atmospheric [CO2 ]; (b) was less affected by higher temperature or decreasing rainfall; and (c) was more affected by increased rainfall because N leaching was more critical. The model intercomparison revealed that simulation of daily soil N supply and N leaching plays a crucial role in simulating climate change impacts for low-input systems. Climate change and N input interactions have strong implications for the design of robust adaptation approaches across SSA, because the impact of climate change in low input systems will be modified if farmers intensify maize production with balanced nutrient management.

Correction: Spatially heterogeneous dynamics of cells in a growing tumor spheroid: comparison between theory and experiments.

Correction for 'Spatially heterogeneous dynamics of cells in a growing tumor spheroid: comparison between theory and experiments' by Sumit Sinha et al., Soft Matter, 2020, 16, 5294-5304, DOI: .

Spatially heterogeneous dynamics of cells in a growing tumor spheroid: comparison between theory and experiments.

Collective cell movement, characterized by multiple cells that are in contact for substantial periods of time and undergo correlated motion, plays a central role in cancer and embryogenesis. Recent imaging experiments have provided time-dependent traces of individual cells, thus providing an unprecedented picture of tumor spheroid growth. By using simulations of a minimal cell model, we analyze the experimental data that map the movement of cells in a fibrosarcoma tumor spheroid embedded in a collagen matrix. Both simulations and experiments show that cells in the core of the spheroid exhibit subdiffusive glassy dynamics (mean square displacement, Δ(t) ≈ tα with α < 1), whereas cells in the periphery exhibit superdiffusive motion, Δ(t) ≈ tα with α > 1. The motion of most of the cells near the periphery is highly persistent and correlated directional motion due to cell doubling and apoptosis rates, thus explaining the observed superdiffusive behavior. The α values for cells in the core and periphery, extracted from simulations and experiments, are in near quantitative agreement with each other, which is surprising given that no parameter in the model was used to fit the measurements. The qualitatively different dynamics of cells in the core and periphery is captured by the fourth order susceptibility, introduced to characterize metastable states in glass forming systems. Analyses of the velocity autocorrelation of individual cells show remarkable spatial heterogeneity with no two cells exhibiting similar behavior. The prediction that α should depend on the location of the cells in the tumor is amenable to experimental testing. The highly heterogeneous dynamics of cells in the tumor spheroid provides a plausible mechanism for the origin of intratumor heterogeneity.

Can nature-based solutions contribute to water security in Bhopal?

Bhojtal, a large man-made lake bordering the city of Bhopal (Madhya Pradesh state, central India), is important for the city's water supply, connoted the lifeline of the city. Despite the dry though not arid and markedly seasonal climate, soil impermeability hampers infiltration into the complex geology underlying the Bhojtal catchment. Rural communities in the catchment are nonetheless high dependent on underlying aquifers. This paper develops baseline understanding of trends in the ecology, water quality and uses of Bhojtal, discussing their implications for the long-term wellbeing of the Bhopal city region. It highlights increasing dependency on water diverted from out-of-catchment sources, and also abstraction across the Bhojtal catchment in excess of replenishment that is depressing groundwater and contributing to reported declining lake level and water quality. Despite some nature-based management initiatives, evidence suggests little progress in haltering on-going groundwater depression and declines in lake water level and quality. Significant declines in ecosystem services produced by Bhojtal are likely without intervention, a major concern given the high dependency of people in the Bhopal region on Bhojtal for their water supply and socio-economic and cultural wellbeing. Over-reliance on appropriation of water from increasingly remote sources is currently compensating for lack of attention to measures protecting or regenerating local resources that may provide greater resilience and regional self-sufficiency. Improved knowledge of catchment hydrogeology on a highly localised scale could improve the targeting and efficiency of water harvesting and other management interventions in the Bhojtal catchment, and their appropriate hybridisation with engineered solutions, protecting the catchment from unintended impacts of water extraction or increasing its carrying capacity, and also providing resilience to rising population and climate change. Ecosystem service assessment provides useful insights into the breadth of benefits of improved management of Bhojtal and its catchment.

Spinopelvic parameters in patients with lumbar degenerative disc disease, spondylolisthesis, and failed back syndrome: Comparison vis-à-vis normal asymptomatic population and treatment implications.

BACKGROUND: Most of the literature on role of spinopelvic parameters in various lumbar spine pathologies has been based on studies done on Caucasian population. AIMS AND OBJECTIVES: The present study attempts to establish a database of measurements of the sagittal profile of spine in asymptomatic Indian population and their comparison with subjects having various lumbar spine pathologies. MATERIALS AND METHODS: We performed a prospective case control study at All India Institute of Medical Sciences, New Delhi in which we enrolled 109 patients and 22 healthy asymptomatic subjects in 2 years from 2015 to 2017. All patients underwent standing lateral radiographs of the pelvis and the entire spine and various spino-pelvic parameters were measured using Surgimap software. RESULTS: The mean Pelvic incidence (PI) in the asymptomatic individuals was 49.29 ± 5.95° which was significantly lower when compared with patients of chronic low backache (53.96 ± 9.47, P-<0.001), lumbar listhesis (59.4 ± 21.33, P-<0.001) and failed back surgery syndrome (56.7 ± 8.21, P-<0.001). The mean Pelvic Tilt (PT) in healthy subjects was 14.3±4.08° which was significantly lower when compared with patients of lumbar listhesis (23.35 ± 14.03, P-<0.001) and failed back surgery syndrome (22.8 ± 8.09, P-<0.001). Sacral slope (SS) and sagittal vertical axis (SVA) offset did not show any statistically significant difference. The mean Lumbar lordosis (LL) measured in healthy individuals was 42.5 ± 7.89° which was significantly lower when compared with patients of lumbar listhesis (46.24 ± 19.24, P-0.04) and failed back surgery syndrome (45.12 ± 6.87, P-0.05). CONCLUSION: PT and PI showed statistically significant difference in subjects having lumbar spondylolisthesis and failed back surgery syndrome as compared to healthy asymptomatic subjects.

Cervical Spondylotic Myelopathy: Natural Course and the Value of Diagnostic Techniques -WFNS Spine Committee Recommendations.

OBJECTIVE: This study presents the results of a systematic literature review conducted to determine most up-to-date information on the natural outcome of cervical spondylotic myelopathy (CSM) and the most reliable diagnostic techniques. METHODS: A literature search was performed for articles published during the last 10 years. RESULTS: The natural course of patients with cervical stenosis and signs of myelopathy is quite variable. In patients with no symptoms, but significant stenosis, the risk of developing myelopathy with cervical stenosis is approximately 3% per year. Myelopathic signs are useful for the clinical diagnosis of CSM. However, they are not highly sensitive and may be absent in approximately one-fifth of patients with myelopathy. The electrophysiological tests to be used in CSM patients are motor evoked potential (MEP), spinal cord evoked potential, somatosensory evoked potential, and electromyography (EMG). The differential diagnosis of CSM from other neurological conditions can be accomplished by those tests. MEP and EMG monitoring are useful to reduce C5 root palsy during CSM surgery. Notable spinal cord T2 hyperintensity on cervical magnetic resonance imaging (MRI) is correlated with a worse outcome, whereas lighter signal changes may predict better outcomes. T1 hypointensity should be considered a sign of more advanced disease. CONCLUSION: The natural course of CSM is quite variable. Signal changes on MRI and some electrophysiological tests are valuable adjuncts to diagnosis.

Cervical rotation before and after hinge-door cervical laminoplasty for cervical spondylotic myelopathy.

BACKGROUND: Hinge-Door Cervical laminoplasty is commonly performed procedure in patients with cervical spondylotic myelopathy. Most available studies have established restriction of flexion and extension motion post laminoplasty but the literature on post-laminoplasty axial rotation is sparse. OBJECTIVE: To study the axial neck rotation on either side following hinge door cervical laminoplasty. MATERIALS AND METHODS: Twenty consecutive patients of cervical spondylotic myelopathy planned for cervical laminoplasty were included in the study. Preoperative and postoperative radiological data was recorded for each patient and analysed by an experienced neuroradiologist. The clinical and radiological follow-up was recorded at 6 months post surgery. All patients underwent standard hinge door C3-C6 laminoplasty preserving the muscle attachments to C2 and C7 vertebra. RESULTS: There were 13 men and 7 women with a mean age of 60.5 years, age range 58-70 years. The mean preop C1 C2 rotation was 46.5 degrees and mean post-operative C1-C2 rotation was 44.3 degrees. The average subaxial cervical spine rotation was 11.66 degrees preoperatively and 12.47 degrees postoperatively. The global cervical spine rotation was 80.95 degrees preoperatively and 76.82 degrees postoperatively. There is no significant change in segmental, subaxial and global cervical spine rotation following hinge door C3-C6 laminoplasty preserving the muscle attachments to C2 and C7 vertebra. CONCLUSION: Cervical laminoplasty preserves cervical ROM and is a motion-preserving surgery as far as axial rotation is concerned.

Intracranial Pressure Monitoring in Children with Severe Traumatic Brain Injury: A Retrospective Study.

INTRODUCTION: There is a paucity of literature on intracranial pressure (ICP) monitoring in children. The aim of this study was to ascertain whether ICP monitoring is useful in children with severe traumatic brain injury (TBI). MATERIALS AND METHODS: Medical records of children between 1 and 12 years, admitted to neurocritical care unit with severe TBI in 2 years, were reviewed. The children were divided into two groups: study group (ICP monitored) and control group (ICP not monitored). Admission demographics, vital parameters, and computed tomographic scan findings were recorded. In the study group, date of ICP catheter insertion/removal with ICP values and treatment carried out for increased ICP were noted. Data on tracheostomy, duration of mechanical ventilation, hospital stay, and outcome at discharge were noted. RESULTS: Demographic variables were comparable between the two groups. When adjusted for death, no significant difference was observed between the study and the control groups in median duration of mechanical ventilation: 35 days (95% confidence interval [CI]: 12-73) versus 55 days (95% CI: 29-55) (P = 0.96), hospital stay: 36 days (95% CI: 12-73) versus 58 days (95% CI: 29-58) (P = 0.96), and time to tracheostomy: 6 days (95% CI: 5-8) versus 5 days (95% CI: 4-7) (P = 0.49). Mortality rates, incidence of cranial surgeries, and outcome at discharge were also comparable. CONCLUSION: ICP monitoring did not reduce the incidence of death, cranial surgeries, duration of mechanical ventilation, hospital stay, or improve the outcome at discharge in children with severe TBI.