Interleukin 6 plays a role in the migration of magnetically levitated mesenchymal stem cells spheroids

Mesenchymal stem cells (MSCs) reside quiescently within a specialised ‘niche’ environment in the bone marrow. However, following appropriate signalling cues, MSCs mobilise and migrate out from the niche, typically toward either sites of injury (a regenerative response) or toward primary tumours (an intrinsic homing response, which promotes MSCs as cellular vectors for therapeutic delivery). To date, very little is known about MSC mobilisation. By adopting a 3D MSC niche model, whereby MSC spheroids are cultured within a type I collagen gel, recent studies have highlighted interleukin-6 (IL-6) as a key cytokine involved in MSC migration. Herein, the ability of IL-6 to induce MSC migration was further investigated, and the key matrix metalloproteinases used to effect cell mobilisation were identified. Briefly, the impact of IL-6 on the MSC migration in a two-dimensional model systems was characterised—both visually using an Ibidi chemotaxis plate array (assessing for directional migration) and then via a standard 2D monolayer experiment, where cultured cells were challenged with IL-6 and extracted media tested using an Abcam Human MMP membrane antibody array. The 2D assay displayed a strong migratory response toward IL-6 and analysis of the membrane arrays data showed significant increases of several key MMPs. Both data sets indicated that IL-6 is important in MSC mobilisation and migration. We also investigated the impact of IL-6 induction on MSCs in 3D spheroid culture, serving as a simplistic model of the bone marrow niche, characterised by fluorescently tagged magnetic nanoparticles and identical membrane antibody arrays. An increase in MMP levels secreted by cells treated with 1 ng/mL IL-6 versus control conditions was noted in addition to migration of cells away from the central spheroid mass

Computational Notebooks as Co-Design Tools:Engaging Young Adults Living with Diabetes, Family Carers, and Clinicians with Machine Learning Models

Engaging end user groups with machine learning (ML) models can help align the design of predictive systems with people's needs and expectations. We present a co-design study investigating the benefits and challenges of using computational notebooks to inform ML models with end user groups. We used a computational notebook to engage young adults, carers, and clinicians with an example ML model that predicted health risk in diabetes care. Through co-design workshops and retrospective interviews, we found that participants particularly valued using the interactive data visualisations of the computational notebook to scaffold multidisciplinary learning, anticipate benefits and harms of the example ML model, and create fictional feature importance plots to highlight care needs. Participants also reported challenges, from running code cells to managing information asymmetries and power imbalances. We discuss the potential of leveraging computational notebooks as interactive co-design tools to meet end user needs early in ML model lifecycles

Observations and Dynamical Implications of Active Normal Faulting in South Peru

Orogenic plateaus can exist in a delicate balance in which the buoyancy forces due to gravity acting on the high topography and thick crust of the plateau interior are balanced by the compressional forces acting across their forelands. Any shortening or extension within a plateau can indicate a perturbation to this force balance. In this study we present new observations of the kinematics, morphology and slip rates of active normal faults in the South Peruvian Altiplano obtained from field studies, high-resolution DEMs, Quaternary dating and remote sensing. We then investigate the implications of this faulting for the forces acting on the Andes. We find that the mountains are extending NNE-SSW to NE-SW along a normal fault system that cuts obliquely across the Altiplano plateau, which in many places reactivates Miocene-age reverse faults. Radiocarbon dating of offset late Quaternary moraines and alluvial fan surfaces indicates horizontal extension rates across the fault system of between 1 and 4 mm/yr — equivalent to an extensional strain rate in the range of 0.5-2×10−8 1/yr averaged across the plateau. We suggest the rate and pattern of extension implies there has been a change in the forces exerted between the foreland and the Andes mountains. A reduction in the average shear stresses on the sub-Andean foreland detachment of <4 MPa (<20-25% of the total force) can account for the rate of extension. These results show that, within a mountain belt, the pattern of faulting is sensitive to small spatial and temporal variations in the strength of faults along their margins

Direct and ozone-mediated forcing of the Southern Annular Mode by greenhouse gases

We assess the roles of long-lived greenhouse gases and ozone depletion in driving meridional surface pressure gradients in the southern extratropics; these gradients are a defining feature of the Southern Annular Mode. Stratospheric ozone depletion is thought to have caused a strengthening of this mode during summer, with increasing long-lived greenhouse gases playing a secondary role. Using a coupled atmosphere-ocean chemistry-climate model, we show that there is cancelation between the direct, radiative effect of increasing greenhouse gases by the also substantial indirect—chemical and dynamical—feedbacks that greenhouse gases have via their impact on ozone. This sensitivity of the mode to greenhouse gas-induced ozone changes suggests that a consistent implementation of ozone changes due to long-lived greenhouse gases in climate models benefits the simulation of this important aspect of Southern Hemisphere climate

Understanding the relationships between self-esteem, experiential avoidance, and paranoia: structural equation modelling and experience sampling studies

Hypothesized relationships between experiential avoidance (EA), self-esteem, and paranoia were tested using structural equation modeling in a sample of student participants (N = 427). EA in everyday life was also investigated using the Experience Sampling Method in a subsample of students scoring high (N = 17) and low (N = 15) on paranoia. Results showed that paranoid students had lower self-esteem and reported higher levels of EA than nonparanoid participants. The interactive influence of EA and stress predicted negative self-esteem: EA was particularly damaging at high levels of stress. Greater EA and higher social stress independently predicted lower positive self-esteem. Low positive self-esteem predicted engagement in EA. A direct association between EA and paranoia was also found. These results suggest that similar mechanisms may underlie EA and thought suppression. Although people may employ EA to regulate self-esteem, this strategy is maladaptive as it damages self-esteem, incurs cognitive costs, and fosters paranoid thinking.status: publishe

Observations and dynamical implications of active normal faulting in South Peru

Orogenic plateaus can exist in a delicate balance in which the buoyancy forces due to gravity acting on the high topography and thick crust of the plateau interior are balanced by the compressional forces acting across their forelands. Any shortening or extension within a plateau can indicate a perturbation to this force balance. In this study we present new observations of the kinematics, morphology and slip rates of active normal faults in the South Peruvian Altiplano obtained from field studies, high resolution DEMs, Quaternary dating and remote sensing. We then investigate the implications of this faulting for the forces acting on the Andes. We find that the mountains are extending ~NNE-SSW to ~NE-SW along a normal fault system that cuts obliquely across the Altiplano plateau, which in many places reactivates Miocene age reverse faults. Radiocarbon dating of o set late Quaternary moraines and alluvial fan surfaces indicates horizontal extension rates across the fault system of between 1 and 4 mm/yr -equivalent to an extensional strain rate in the range of 0.5-2 x 10 -8 1/yr averaged across the plateau. We suggest the rate and pattern of extension implies there has been a change in the forces exerted between the foreland and the Andes mountains. A reduction in the average shear stresses on the sub-Andean foreland detachment of ≤4 MPa (20-25% of the total force) can account for the rate of extension. These results show that, within a mountain belt, the pattern of faulting is sensitive to small spatial and temporal variations in the strength of faults along their margins