The chromatin state of pluripotency genes has been studied extensively in embryonic stem cells (ESCs) and differentiated cells, but their potential interactions with other parts of the genome remain ...largely unexplored. Here, we identified a genome-wide, pluripotency-specific interaction network around the Nanog promoter by adapting circular chromosome conformation capture sequencing. This network was rearranged during differentiation and restored in induced pluripotent stem cells. A large fraction of Nanog-interacting loci were bound by Mediator or cohesin in pluripotent cells. Depletion of these proteins from ESCs resulted in a disruption of contacts and the acquisition of a differentiation-specific interaction pattern prior to obvious transcriptional and phenotypic changes. Similarly, the establishment of Nanog interactions during reprogramming often preceded transcriptional upregulation of associated genes, suggesting a causative link. Our results document a complex, pluripotency-specific chromatin “interactome” for Nanog and suggest a functional role for long-range genomic interactions in the maintenance and induction of pluripotency.
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•The Nanog promoter forms a pluripotency-specific, genome-wide chromatin interactome•Nanog interactions in ESCs are enriched for active marks and pluripotency factors•Mediator and cohesin are essential for the maintenance of the Nanog interactome•Many Nanog interactions form before increased gene expression during reprogramming
The Nanog promoter interacts with the rest of the genome in an unexpectedly complex pluripotency-specific chromatin interaction network that depends on Mediator and cohesin.
The promise of oceanic discovery has long intrigued scientists and explorers, whether with the idea of studying underwater ecology and climate change or with the hope of uncovering natural resources ...and historic secrets buried deep in archaeological sites. This quest to explore the oceans requires skilled human access, yet much of the oceans are inaccessible to human divers; nearly ninetenths of the ocean floor is at 1 km or deeper 1. Accessing these depths is imperative since factors such as pollution and deep-sea trawling threaten ecology and archaeological sites. While remotely operated vehicles (ROVs) are inadequate for the task, a robotic avatar could go where humans cannot and still embody human intelligence and intentions through immersive interfaces.
Upper-limb prosthesis users continue to reject devices despite continued research efforts. Today, the passive topology of body-powered prehensors, which physically transmits grasp force and position ...data between user and device, results in improved performance over myoelectric alternatives. However, the loads and postures on the user's body also result in discomfort, fatigue, and worsened grasp force control. Despite the long history and everyday adoption of body-powered prehensors in society, the measurement of how specific body loads and postures affect grasp performance and user experience has yet to be systematically studied. In this work, we present a body-powered prosthesis emulator to independently change required input forces and motions to study the positive and negative effects provided by the inherent haptic feedback. Using a simulated grasping task, we collect functional and qualitative data from 15 participants using a shoulder harness interface. Outcomes show that lowering required input motions and forces independently reduces negative outcomes, with diminishing returns below 1:1 output mappings. Given the tradeoff between force and motion in traditional body-powered transmissions, a transmission ratio of 1:1 balances both requirements. The purpose of this study is to inform future prehensor designs that leverage the transparency of body-power to deliver high functionality while mitigating user discomfort.
Underactuated, compliant, tendon-driven robotic hands are suited for deep-sea exploration. The robust Ocean One hand design utilizes elastic finger joints and a spring transmission to achieve a ...variety of pinch and wrap grasps. Compliance in the fingers and transmission determines the degree of load-sharing among contacts and the hands’ ability to secure irregularly shaped objects. However, it can also decrease external grasp stiffness and acquisition reliability. SimGrasp, a flexible dynamic hand simulator, enables parametric studies of the hand for acquisition and pull-out tests with varying transmission spring rates. In the present application, we take advantage of achieving different stiffnesses by reversing the direction of tendon windup using a torsional spring-loaded winch. With this provision, the hand can be relatively soft for handling delicate objects and stiff for tasks requiring strength. Two hands were field-tested as part of the Ocean One humanoid platform, which acquired a vase from the La Lune shipwreck site at a 91 m depth in the Mediterranean Sea.
Gentle suction flow at the fingertips of a compliant hand can enhance object acquisition and increase the robustness of pinch grasps under water. The approach adds a low-pressure pump and flexible ...tubes that terminate at the distal phalanges. The light flow rate does not create a powerful suction force, nor does it stir up significant sediment. The method works on porous and rough objects in addition to smooth objects as it does not require forming a seal. It changes contact conditions - normal force and coefficient of friction - and enlarges the acquisition region when grasping free objects under water. A simple hydrodynamic model matches empirical force measurements adequately for incorporation in a dynamic simulation to explore the effects of flow rate and object mass. Simulations and experiments show that effects of fingertip suction flow are most pronounced for acquiring objects on the order of 1 kg or less and when pinching large objects. Gentle suction flow is an effective, versatile, and convenient addition for robots that must grasp and manipulate objects under water.
Studies of mechanical signalling are typically performed by comparing cells cultured on soft and stiff hydrogel-based substrates. However, it is challenging to independently and robustly control both ...substrate stiffness and extracellular matrix tethering to substrates, making matrix tethering a potentially confounding variable in mechanical signalling investigations. Moreover, unstable matrix tethering can lead to poor cell attachment and weak engagement of cell adhesions. To address this, we developed StemBond hydrogels, a hydrogel in which matrix tethering is robust and can be varied independently of stiffness. We validate StemBond hydrogels by showing that they provide an optimal system for culturing mouse and human pluripotent stem cells. We further show how soft StemBond hydrogels modulate stem cell function, partly through stiffness-sensitive ERK signalling. Our findings underline how substrate mechanics impact mechanosensitive signalling pathways regulating self-renewal and differentiation, indicating that optimising the complete mechanical microenvironment will offer greater control over stem cell fate specification.
A hallmark of naive pluripotency is the presence of two active X chromosomes in females. It is not clear whether prevention of X chromosome inactivation (XCI) is mediated by gene networks that ...preserve the naive state. Here, we show that robust naive pluripotent stem cell (nPSC) self-renewal represses expression of Xist, the master regulator of XCI. We found that nPSCs accumulate Xist on the male X chromosome and on both female X chromosomes as they become NANOG negative at the onset of differentiation. This is accompanied by the appearance of a repressive chromatin signature and partial X-linked gene silencing, suggesting a transient and rapid XCI-like state in male nPSCs. In the embryo, Xist is transiently expressed in males and in females from both X chromosomes at the onset of naive epiblast differentiation. In conclusion, we propose that XCI initiation is gender independent and triggered by destabilization of naive identity, suggesting that gender-specific mechanisms follow, rather than precede, XCI initiation.
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•A robust naive pluripotent transcription factor network abolishes expression of Xist•Xist accumulates on the male X and both female Xs at the onset of differentiation•Males undergo transient and rapid partial XCI•Male XCI is triggered by downregulation of the naive identity
Silva and colleagues report that the initiation of X chromosome inactivation takes place in males and on both X chromosomes in females. This is transient and rapid and is triggered by downregulation of naive pluripotent transcription factors during the onset of differentiation.
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•A flexible, thin-film carbon electrode developed for detection of dopamine.•The electrode was electrochemically characterised to assess its sensitivity.•The electrode provided a ...dopamine limit of detection of ~50 pM.•Good selectivity shown between dopamine and key interferent, ascorbic acid.
A flexible, thin-film carbon electrode is reported for detection of the key neurotransmitter dopamine using standard electroanalytical techniques of cyclic voltammetry, differential pulse voltammetry and square wave voltammetry. The thin-film electrode has been explored as a possible low-cost solution to detect low concentrations of dopamine and its performance has been compared with a commercially available screen printed carbon electrode. It was found that the thin-film electrode is more sensitive than the screen printed electrode, and can faithfully detect dopamine between 50 pM and 1 mM concentrations. The electrode provides a limit of detection of ~50 pM, displays good selectivity between dopamine and ascorbic acid, and is able to show a level of differentiation between the two compounds in terms of peak currents as well as oxidative potentials at physiologically relevant concentrations. This is in contrast to the screen printed electrode which is unable to discriminate between dopamine and ascorbic acid at the same concentrations. The key advantages of the presented electrode system are its low-cost, flexible substrate, and the ability to achieve very low levels of dopamine detection without requiring any electrode surface modification steps, a key factor in reducing fabrication costs and overall device complexity.
A multifunctional sensor that responds to all – static/quasi-static or dynamic temperature or force – is reported. The sensor is based on a ferroelectric poly(vinylidene fluoride trifluoroethylene) ...(P(VDF-TrFE)) capacitor connected to the gate of organic field-effect transistor (OFET). Both, the P(VDF-TrFE) capacitance and the output voltage of the P(VDF-TrFE)/OFET sensor exhibit a logarithmic response to static compressive force, leading to higher sensitivity for small forces. In addition, both the P(VDF-TrFE) capacitance and the output voltage of the P(VDF-TrFE)/OFET sensor exhibit a linear dependence on the static/constant temperature. Response to static force or temperature is observed irrespective of whether P(VDF-TrFE) is in ferroelectric or paraelectric states, confirming that piezo/pyroelectricity is not essential when monitoring static events. The piezo/pyroelectricity become activated during dynamic events (dynamic force or temperature) when the ferroelectric P(VDF-TrFE)/OFET sensor is used. The obtained results indicate different sensing mechanisms for static and dynamic stimuli. Consequently, by choosing P(VDF-TrFE) layers in ferroelectric or paraelectric states a route for differentiating between the static and dynamic stimuli may exist.
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•Multifunctional sensor based on P(VDF-TrFE) and low-voltage organic transistor.•The sensor responds to static/constant and dynamic/changing force or temperature.•Different P(VDF-TrFE) properties are used for sensing static vs. dynamic stimuli.•P(VDF-TrFE)/OFET sensors exhibits logarithmic response to static force.•P(VDF-TrFE)/OFET sensors exhibits linear response to static temperature.
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