Innate immunity offers the first line of defense against infections and other types of danger such as tumorigenesis. Its discovery provides tremendous therapeutic opportunities for numerous human diseases. Delving int...Innate immunity offers the first line of defense against infections and other types of danger such as tumorigenesis. Its discovery provides tremendous therapeutic opportunities for numerous human diseases. Delving into the structural basis of signal transduction by innate immune receptors, our lab has recently helped to establish the new paradigm in which innate immune receptors transduce ligand-binding signals through formation of higher-order assemblies containing intracellular adapters, signaling enzymes and their substrates. These large signalosome assemblies may be visible under light microscopy as punctate structures in the μm scale, connecting to the underlying molecular structures in the nm scale. They drive proximity-induced enzyme activation, and provide a mechanism for signaling amplification by nucleated polymerization. These supramolecular signaling complexes also open new questions on their cellular organization and mode of regulation, pose challenges to our methodology, and afford valuable implications in drug discovery against these medically important pathways.展开更多
Mechanical cues present in the stem cell niche resulting from intracellular processes or external force sources significantly affect the basic functions of stem cells such as self-renewal and differentiation.Creation ...Mechanical cues present in the stem cell niche resulting from intracellular processes or external force sources significantly affect the basic functions of stem cells such as self-renewal and differentiation.Creation of artificial cellular matrices exhibiting intrinsic mechanical cues generated by mechanical movements remains scarce.Herein,we reported on mechanically dynamic hydrogel matrices undergoing photo-induced directional domain sliding movement and their role in regulating embryonic stem cell(ESC)differentiation.The mechanically dynamic hydrogels were prepared via the self-assembly of an alternating hydrophilic and hydrophobic peptide with a photocaged cysteine residue.Upon light irradiation,the assemblies of the caged peptide were converted to non-equilibrated non-caged peptide bilayers that underwent the directional domain sliding motion induced by the thermodynamically favorable hydrophobic collapse transition.Culturing murine ESCs on the mechanically dynamic hydrogels resulted in biased differentiation toward the ectodermal lineage.We further showed that the mechanically dynamic hydrogels stimulated the translocation of a mechanotransduction protein Yes-associated protein(YAP)into the nucleus,implicating a potential mechanotransduction mechanism for the biased differentiation of ESCs.The finding of the biased ectodermal differentiation of ESCs induced by the mechanically dynamic hydrogels implies the great potency of the mechanically dynamic hydrogels as biomaterials for disease therapy and tissue regeneration in the future.展开更多
Although salamanders have been shown to respond to classical conditioning, spatial learning has been largely unstudied. We tested whether salamanders could learn to locate foraging areas by using landmarks. We trained...Although salamanders have been shown to respond to classical conditioning, spatial learning has been largely unstudied. We tested whether salamanders could learn to locate foraging areas by using landmarks. We trained 10 salamanders Plethodon angusticlavius to use landmarks （small rocks） to locate patches within the arena containing food （blackworms Lumbriculus variegatus）. At the comers of each square testing arena were four plastic dishes, one containing blackworms and the other three empty. A rock was placed in front of the dish containing blackworms, and the location of the food-dish was randomly chosen for each training trial. A control group was also trained to feed on blackworms in the presence of a rock, but the rock was positioned randomly among the four dish locations so that the rock was not a reliable landmark for the worms. Although the length of the training period for individual salamanders varied （22-38 trainings per individual）, the mean number of trainings for salamanders in the control and experimental groups was equal （30 training trials）. During testing, no blackworms were present to eliminate any visual or chemical cues emanating directly from the prey. Individuals trained with the rock landmarks spent sig- nificantly more time in the area of the landmark than did control salamanders [Current Zoology 57 （4）： 485-490, 2011].展开更多
文摘Innate immunity offers the first line of defense against infections and other types of danger such as tumorigenesis. Its discovery provides tremendous therapeutic opportunities for numerous human diseases. Delving into the structural basis of signal transduction by innate immune receptors, our lab has recently helped to establish the new paradigm in which innate immune receptors transduce ligand-binding signals through formation of higher-order assemblies containing intracellular adapters, signaling enzymes and their substrates. These large signalosome assemblies may be visible under light microscopy as punctate structures in the μm scale, connecting to the underlying molecular structures in the nm scale. They drive proximity-induced enzyme activation, and provide a mechanism for signaling amplification by nucleated polymerization. These supramolecular signaling complexes also open new questions on their cellular organization and mode of regulation, pose challenges to our methodology, and afford valuable implications in drug discovery against these medically important pathways.
基金supported by the National Key R&D Program of China (2018YFC1313003)the Fundamental Research Funds for the Central Universities+1 种基金the National Natural Science Foundation of China (21774065 and 31622038)the Natural Science Foundation of Tianjin (18JCQNJC14100 and 18JCJQJC48400)
文摘Mechanical cues present in the stem cell niche resulting from intracellular processes or external force sources significantly affect the basic functions of stem cells such as self-renewal and differentiation.Creation of artificial cellular matrices exhibiting intrinsic mechanical cues generated by mechanical movements remains scarce.Herein,we reported on mechanically dynamic hydrogel matrices undergoing photo-induced directional domain sliding movement and their role in regulating embryonic stem cell(ESC)differentiation.The mechanically dynamic hydrogels were prepared via the self-assembly of an alternating hydrophilic and hydrophobic peptide with a photocaged cysteine residue.Upon light irradiation,the assemblies of the caged peptide were converted to non-equilibrated non-caged peptide bilayers that underwent the directional domain sliding motion induced by the thermodynamically favorable hydrophobic collapse transition.Culturing murine ESCs on the mechanically dynamic hydrogels resulted in biased differentiation toward the ectodermal lineage.We further showed that the mechanically dynamic hydrogels stimulated the translocation of a mechanotransduction protein Yes-associated protein(YAP)into the nucleus,implicating a potential mechanotransduction mechanism for the biased differentiation of ESCs.The finding of the biased ectodermal differentiation of ESCs induced by the mechanically dynamic hydrogels implies the great potency of the mechanically dynamic hydrogels as biomaterials for disease therapy and tissue regeneration in the future.
文摘Although salamanders have been shown to respond to classical conditioning, spatial learning has been largely unstudied. We tested whether salamanders could learn to locate foraging areas by using landmarks. We trained 10 salamanders Plethodon angusticlavius to use landmarks （small rocks） to locate patches within the arena containing food （blackworms Lumbriculus variegatus）. At the comers of each square testing arena were four plastic dishes, one containing blackworms and the other three empty. A rock was placed in front of the dish containing blackworms, and the location of the food-dish was randomly chosen for each training trial. A control group was also trained to feed on blackworms in the presence of a rock, but the rock was positioned randomly among the four dish locations so that the rock was not a reliable landmark for the worms. Although the length of the training period for individual salamanders varied （22-38 trainings per individual）, the mean number of trainings for salamanders in the control and experimental groups was equal （30 training trials）. During testing, no blackworms were present to eliminate any visual or chemical cues emanating directly from the prey. Individuals trained with the rock landmarks spent sig- nificantly more time in the area of the landmark than did control salamanders [Current Zoology 57 （4）： 485-490, 2011].
