We specifically focus on the locomotion of the blob to understand how an amorphous entangled ball of worms can break symmetry to move across a substrate. We hypothesize that the collective blob displays rudimentary differentiation of function across itself, which when combined with entanglement dynamics facilitates directed persistent blob locomotion. To test this, we develop a robophysical model of the worm blobs, which displays emergent locomotion in the collective without sophisticated control or programming of any individual robot. The emergent dynamics of the living functional blob and robophysical model can inform the design of additional classes of adaptive mechanofunctional living materials and emergent robotics.Color vision has evolved multiple times in both vertebrates and invertebrates and is largely determined by the number and variation in spectral sensitivities of distinct opsin subclasses. However, because of the difficulty of expressing long-wavelength (LW) invertebrate opsins in vitro, our understanding of the molecular basis of functional shifts in opsin spectral sensitivities has been biased toward research primarily in vertebrates. This has restricted our ability to address whether invertebrate Gq protein-coupled opsins function in a novel or convergent way compared to vertebrate Gt opsins. Here we develop a robust heterologous expression system to purify invertebrate rhodopsins, identify specific amino acid changes responsible for adaptive spectral tuning, and pinpoint how molecular variation in invertebrate opsins underlie wavelength sensitivity shifts that enhance visual perception. By combining functional and optophysiological approaches, we disentangle the relative contributions of lateral filtering pigments from red-shifted LW and blue short-wavelength opsins expressed in distinct photoreceptor cells of individual ommatidia. We use in situ hybridization to visualize six ommatidial classes in the compound eye of a lycaenid butterfly with a four-opsin visual system. We show experimentally that certain key tuning residues underlying green spectral shifts in blue opsin paralogs have evolved repeatedly among short-wavelength opsin lineages. Taken together, our results demonstrate the interplay between regulatory and adaptive evolution at multiple Gq opsin loci, as well as how coordinated spectral shifts in LW and blue opsins can act together to enhance insect spectral sensitivity at blue and red wavelengths for visual performance adaptation.The Antarctic Ice Sheet loses about half its mass through ocean-driven melting of its fringing ice shelves. However, the ocean processes governing ice shelf melting are not well understood, contributing to uncertainty in projections of Antarctica's contribution to global sea level. We use high-resolution large-eddy simulation to examine ocean-driven melt, in a geophysical-scale model of the turbulent ice shelf-ocean boundary layer, focusing on the ocean conditions observed beneath the Ross Ice Shelf. We quantify the role of double-diffusive convection in determining ice shelf melt rates and oceanic mixed layer properties in relatively warm and low-velocity cavity environments. https://www.selleckchem.com/products/am-095.html We demonstrate that double-diffusive convection is the first-order process controlling the melt rate and mixed layer evolution at these flow conditions, even more important than vertical shear due to a mean flow, and is responsible for the step-like temperature and salinity structure, or thermohaline staircase, observed beneath the ice. A robust feature of the multiday simulations is a growing saline diffusive sublayer that drives a time-dependent melt rate. This melt rate is lower than current ice-ocean parameterizations, which consider only shear-controlled turbulent melting, would predict. Our main finding is that double-diffusive convection is an important process beneath ice shelves, yet is currently neglected in ocean-climate models.What are the cortical neural correlates that distinguish goal-directed and non-goal-directed movements? We investigated this question in the monkey frontal eye field (FEF), which is implicated in voluntary control of saccades. Here, we compared FEF activity associated with goal-directed (G) saccades and non-goal-directed (nG) saccades made by the monkey. Although the FEF neurons discharged before these nG saccades, there were three major differences in the neural activity First, the variability in spike rate across trials decreased only for G saccades. Second, the local field potential beta-band power decreased during G saccades but did not change during nG saccades. Third, the time from saccade direction selection to the saccade onset was significantly longer for G saccades compared with nG saccades. Overall, our results reveal unexpected differences in neural signatures for G versus nG saccades in a brain area that has been implicated selectively in voluntary control. Taken together, these data add critical constraints to the way we think about saccade generation in the brain.Intracellular delivery of messenger RNA (mRNA)-based cancer vaccine has shown great potential to elicit antitumor immunity. To achieve robust antitumor efficacy, mRNA encoding tumor antigens needs to be efficiently delivered and translated in dendritic cells with concurrent innate immune stimulation to promote antigen presentation. Here, by screening a group of cationic lipid-like materials, we developed a minimalist nanovaccine with C1 lipid nanoparticle (LNP) that could efficiently deliver mRNA in antigen presenting cells with simultaneous Toll-like receptor 4 (TLR4) activation and induced robust T cell activation. The C1 nanovaccine entered cells via phagocytosis and showed efficient mRNA-encoded antigen expression and presentation. Furthermore, the C1 lipid nanoparticle itself induced the expression of inflammatory cytokines such as IL-12 via stimulating TLR4 signal pathway in dendritic cells. Importantly, the C1 mRNA nanovaccine exhibited significant antitumor efficacy in both tumor prevention and therapeutic vaccine settings. Overall, our work presents a C1 LNP-based mRNA cancer nanovaccine with efficient antigen expression as well as self-adjuvant property, which may provide a platform for developing cancer immunotherapy for a wide range of tumor types.
We specifically focus on the locomotion of the blob to understand how an amorphous entangled ball of worms can break symmetry to move across a substrate. We hypothesize that the collective blob displays rudimentary differentiation of function across itself, which when combined with entanglement dynamics facilitates directed persistent blob locomotion. To test this, we develop a robophysical model of the worm blobs, which displays emergent locomotion in the collective without sophisticated control or programming of any individual robot. The emergent dynamics of the living functional blob and robophysical model can inform the design of additional classes of adaptive mechanofunctional living materials and emergent robotics.Color vision has evolved multiple times in both vertebrates and invertebrates and is largely determined by the number and variation in spectral sensitivities of distinct opsin subclasses. However, because of the difficulty of expressing long-wavelength (LW) invertebrate opsins in vitro, our understanding of the molecular basis of functional shifts in opsin spectral sensitivities has been biased toward research primarily in vertebrates. This has restricted our ability to address whether invertebrate Gq protein-coupled opsins function in a novel or convergent way compared to vertebrate Gt opsins. Here we develop a robust heterologous expression system to purify invertebrate rhodopsins, identify specific amino acid changes responsible for adaptive spectral tuning, and pinpoint how molecular variation in invertebrate opsins underlie wavelength sensitivity shifts that enhance visual perception. By combining functional and optophysiological approaches, we disentangle the relative contributions of lateral filtering pigments from red-shifted LW and blue short-wavelength opsins expressed in distinct photoreceptor cells of individual ommatidia. We use in situ hybridization to visualize six ommatidial classes in the compound eye of a lycaenid butterfly with a four-opsin visual system. We show experimentally that certain key tuning residues underlying green spectral shifts in blue opsin paralogs have evolved repeatedly among short-wavelength opsin lineages. Taken together, our results demonstrate the interplay between regulatory and adaptive evolution at multiple Gq opsin loci, as well as how coordinated spectral shifts in LW and blue opsins can act together to enhance insect spectral sensitivity at blue and red wavelengths for visual performance adaptation.The Antarctic Ice Sheet loses about half its mass through ocean-driven melting of its fringing ice shelves. However, the ocean processes governing ice shelf melting are not well understood, contributing to uncertainty in projections of Antarctica's contribution to global sea level. We use high-resolution large-eddy simulation to examine ocean-driven melt, in a geophysical-scale model of the turbulent ice shelf-ocean boundary layer, focusing on the ocean conditions observed beneath the Ross Ice Shelf. We quantify the role of double-diffusive convection in determining ice shelf melt rates and oceanic mixed layer properties in relatively warm and low-velocity cavity environments. https://www.selleckchem.com/products/am-095.html We demonstrate that double-diffusive convection is the first-order process controlling the melt rate and mixed layer evolution at these flow conditions, even more important than vertical shear due to a mean flow, and is responsible for the step-like temperature and salinity structure, or thermohaline staircase, observed beneath the ice. A robust feature of the multiday simulations is a growing saline diffusive sublayer that drives a time-dependent melt rate. This melt rate is lower than current ice-ocean parameterizations, which consider only shear-controlled turbulent melting, would predict. Our main finding is that double-diffusive convection is an important process beneath ice shelves, yet is currently neglected in ocean-climate models.What are the cortical neural correlates that distinguish goal-directed and non-goal-directed movements? We investigated this question in the monkey frontal eye field (FEF), which is implicated in voluntary control of saccades. Here, we compared FEF activity associated with goal-directed (G) saccades and non-goal-directed (nG) saccades made by the monkey. Although the FEF neurons discharged before these nG saccades, there were three major differences in the neural activity First, the variability in spike rate across trials decreased only for G saccades. Second, the local field potential beta-band power decreased during G saccades but did not change during nG saccades. Third, the time from saccade direction selection to the saccade onset was significantly longer for G saccades compared with nG saccades. Overall, our results reveal unexpected differences in neural signatures for G versus nG saccades in a brain area that has been implicated selectively in voluntary control. Taken together, these data add critical constraints to the way we think about saccade generation in the brain.Intracellular delivery of messenger RNA (mRNA)-based cancer vaccine has shown great potential to elicit antitumor immunity. To achieve robust antitumor efficacy, mRNA encoding tumor antigens needs to be efficiently delivered and translated in dendritic cells with concurrent innate immune stimulation to promote antigen presentation. Here, by screening a group of cationic lipid-like materials, we developed a minimalist nanovaccine with C1 lipid nanoparticle (LNP) that could efficiently deliver mRNA in antigen presenting cells with simultaneous Toll-like receptor 4 (TLR4) activation and induced robust T cell activation. The C1 nanovaccine entered cells via phagocytosis and showed efficient mRNA-encoded antigen expression and presentation. Furthermore, the C1 lipid nanoparticle itself induced the expression of inflammatory cytokines such as IL-12 via stimulating TLR4 signal pathway in dendritic cells. Importantly, the C1 mRNA nanovaccine exhibited significant antitumor efficacy in both tumor prevention and therapeutic vaccine settings. Overall, our work presents a C1 LNP-based mRNA cancer nanovaccine with efficient antigen expression as well as self-adjuvant property, which may provide a platform for developing cancer immunotherapy for a wide range of tumor types.
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