Active membrane transport of plant hormones and their related compounds is an essential process that determines the distribution of the compounds within plant tissues and, hence, regulates various physiological events. Here, we report that the Arabidopsis NITRATE TRANSPORTER 1/PEPTIDE TRANSPORTER FAMILY 7.3 (NPF7.3) protein functions as a transporter of indole-3-butyric acid (IBA), a precursor of the major endogenous auxin indole-3-acetic acid (IAA). When expressed in yeast, NPF7.3 mediated cellular IBA uptake. Loss-of-function npf7.3 mutants showed defective root gravitropism with reduced IBA levels and auxin responses. Nevertheless, the phenotype was restored by exogenous application of IAA but not by IBA treatment. NPF7.3 was expressed in pericycle cells and the root tip region including root cap cells of primary roots where the IBA-to-IAA conversion occurs. Our findings indicate that NPF7.3-mediated IBA uptake into specific cells is required for the generation of appropriate auxin gradients within root tissues.A transplanted stem cell's engagement with a pathologic niche is the first step in its restoring homeostasis to that site. Inflammatory chemokines are constitutively produced in such a niche; their binding to receptors on the stem cell helps direct that cell's "pathotropism." Neural stem cells (NSCs), which express CXCR4, migrate to sites of CNS injury or degeneration in part because astrocytes and vasculature produce the inflammatory chemokine CXCL12. Binding of CXCL12 to CXCR4 (a G protein-coupled receptor, GPCR) triggers repair processes within the NSC. Although a tool directing NSCs to where needed has been long-sought, one would not inject this chemokine in vivo because undesirable inflammation also follows CXCL12-CXCR4 coupling. Alternatively, we chemically "mutated" CXCL12, creating a CXCR4 agonist that contained a strong pure binding motif linked to a signaling motif devoid of sequences responsible for synthetic functions. This synthetic dual-moity CXCR4 agonist not only elicited more extensive and persistent human NSC migration and distribution than did native CXCL 12, but induced no host inflammation (or other adverse effects); rather, there was predominantly reparative gene expression. When co-administered with transplanted human induced pluripotent stem cell-derived hNSCs in a mouse model of a prototypical neurodegenerative disease, the agonist enhanced migration, dissemination, and integration of donor-derived cells into the diseased cerebral cortex (including as electrophysiologically-active cortical neurons) where their secreted cross-corrective enzyme mediated a therapeutic impact unachieved by cells alone. Such a "designer" cytokine receptor-agonist peptide illustrates that treatments can be controlled and optimized by exploiting fundamental stem cell properties (e.g., "inflammo-attraction").The perception of sound textures, a class of natural sounds defined by statistical sound structure such as fire, wind, and rain, has been proposed to arise through the integration of time-averaged summary statistics. Where and how the auditory system might encode these summary statistics to create internal representations of these stationary sounds, however, is unknown. Here, using natural textures and synthetic variants with reduced statistics, we show that summary statistics modulate the correlations between frequency organized neuron ensembles in the awake rabbit inferior colliculus (IC). These neural ensemble correlation statistics capture high-order sound structure and allow for accurate neural decoding in a single trial recognition task with evidence accumulation times approaching 1 s. In contrast, the average activity across the neural ensemble (neural spectrum) provides a fast (tens of milliseconds) and salient signal that contributes primarily to texture discrimination. Intriguingly, perceptual studies in human listeners reveal analogous trends the sound spectrum is integrated quickly and serves as a salient discrimination cue while high-order sound statistics are integrated slowly and contribute substantially more toward recognition. The findings suggest statistical sound cues such as the sound spectrum and correlation structure are represented by distinct response statistics in auditory midbrain ensembles, and that these neural response statistics may have dissociable roles and time scales for the recognition and discrimination of natural sounds.Myostatin (MSTN) is a transforming growth factor-β (TGF-β) family member that normally acts to limit muscle growth. The function of MSTN is partially redundant with that of another TGF-β family member, activin A. MSTN and activin A are capable of signaling through a complex of type II and type I receptors. Here, we investigated the roles of two type II receptors (ACVR2 and ACVR2B) and two type I receptors (ALK4 and ALK5) in the regulation of muscle mass by these ligands by genetically targeting these receptors either alone or in combination specifically in myofibers in ****. We show that targeting signaling in myofibers is sufficient to cause significant increases in muscle mass, showing that myofibers are the direct target for signaling by these ligands in the regulation of muscle growth. Moreover, we show that there is functional redundancy between the two type II receptors as well as between the two type I receptors and that all four type II/type I receptor combinations are utilized in vivo. Targeting signaling specifically in myofibers also led to reductions in overall body fat content and improved glucose metabolism in **** fed either regular chow or a high-fat diet, demonstrating that these metabolic effects are the result of enhanced muscling. We observed no effect, however, on either bone density or muscle regeneration in **** in which signaling was targeted in myofibers. The latter finding implies that MSTN likely signals to other cells, such as satellite cells, in addition to myofibers to regulate muscle homeostasis.Domain walls, commonly occurring at the interface of different phases in solid-state materials, have recently been harnessed at the structural scale to enable additional modes of functionality. Here, we combine experimental, numerical, and theoretical tools to investigate the domain walls emerging upon uniaxial compression in a mechanical metamaterial based on the rotating-squares mechanism. We first show that these interfaces can be generated and controlled by carefully arranging a few phase-inducing defects. https://www.selleckchem.com/products/pentetic-acid.html We establish an analytical model to capture the evolution of the domain walls as a function of the applied deformation. We then employ this model as a guideline to realize interfaces of complex shape. Finally, we show that the engineered domain walls modify the global response of the metamaterial and can be effectively exploited to tune its stiffness as well as to guide the propagation of elastic waves.
Active membrane transport of plant hormones and their related compounds is an essential process that determines the distribution of the compounds within plant tissues and, hence, regulates various physiological events. Here, we report that the Arabidopsis NITRATE TRANSPORTER 1/PEPTIDE TRANSPORTER FAMILY 7.3 (NPF7.3) protein functions as a transporter of indole-3-butyric acid (IBA), a precursor of the major endogenous auxin indole-3-acetic acid (IAA). When expressed in yeast, NPF7.3 mediated cellular IBA uptake. Loss-of-function npf7.3 mutants showed defective root gravitropism with reduced IBA levels and auxin responses. Nevertheless, the phenotype was restored by exogenous application of IAA but not by IBA treatment. NPF7.3 was expressed in pericycle cells and the root tip region including root cap cells of primary roots where the IBA-to-IAA conversion occurs. Our findings indicate that NPF7.3-mediated IBA uptake into specific cells is required for the generation of appropriate auxin gradients within root tissues.A transplanted stem cell's engagement with a pathologic niche is the first step in its restoring homeostasis to that site. Inflammatory chemokines are constitutively produced in such a niche; their binding to receptors on the stem cell helps direct that cell's "pathotropism." Neural stem cells (NSCs), which express CXCR4, migrate to sites of CNS injury or degeneration in part because astrocytes and vasculature produce the inflammatory chemokine CXCL12. Binding of CXCL12 to CXCR4 (a G protein-coupled receptor, GPCR) triggers repair processes within the NSC. Although a tool directing NSCs to where needed has been long-sought, one would not inject this chemokine in vivo because undesirable inflammation also follows CXCL12-CXCR4 coupling. Alternatively, we chemically "mutated" CXCL12, creating a CXCR4 agonist that contained a strong pure binding motif linked to a signaling motif devoid of sequences responsible for synthetic functions. This synthetic dual-moity CXCR4 agonist not only elicited more extensive and persistent human NSC migration and distribution than did native CXCL 12, but induced no host inflammation (or other adverse effects); rather, there was predominantly reparative gene expression. When co-administered with transplanted human induced pluripotent stem cell-derived hNSCs in a mouse model of a prototypical neurodegenerative disease, the agonist enhanced migration, dissemination, and integration of donor-derived cells into the diseased cerebral cortex (including as electrophysiologically-active cortical neurons) where their secreted cross-corrective enzyme mediated a therapeutic impact unachieved by cells alone. Such a "designer" cytokine receptor-agonist peptide illustrates that treatments can be controlled and optimized by exploiting fundamental stem cell properties (e.g., "inflammo-attraction").The perception of sound textures, a class of natural sounds defined by statistical sound structure such as fire, wind, and rain, has been proposed to arise through the integration of time-averaged summary statistics. Where and how the auditory system might encode these summary statistics to create internal representations of these stationary sounds, however, is unknown. Here, using natural textures and synthetic variants with reduced statistics, we show that summary statistics modulate the correlations between frequency organized neuron ensembles in the awake rabbit inferior colliculus (IC). These neural ensemble correlation statistics capture high-order sound structure and allow for accurate neural decoding in a single trial recognition task with evidence accumulation times approaching 1 s. In contrast, the average activity across the neural ensemble (neural spectrum) provides a fast (tens of milliseconds) and salient signal that contributes primarily to texture discrimination. Intriguingly, perceptual studies in human listeners reveal analogous trends the sound spectrum is integrated quickly and serves as a salient discrimination cue while high-order sound statistics are integrated slowly and contribute substantially more toward recognition. The findings suggest statistical sound cues such as the sound spectrum and correlation structure are represented by distinct response statistics in auditory midbrain ensembles, and that these neural response statistics may have dissociable roles and time scales for the recognition and discrimination of natural sounds.Myostatin (MSTN) is a transforming growth factor-β (TGF-β) family member that normally acts to limit muscle growth. The function of MSTN is partially redundant with that of another TGF-β family member, activin A. MSTN and activin A are capable of signaling through a complex of type II and type I receptors. Here, we investigated the roles of two type II receptors (ACVR2 and ACVR2B) and two type I receptors (ALK4 and ALK5) in the regulation of muscle mass by these ligands by genetically targeting these receptors either alone or in combination specifically in myofibers in mice. We show that targeting signaling in myofibers is sufficient to cause significant increases in muscle mass, showing that myofibers are the direct target for signaling by these ligands in the regulation of muscle growth. Moreover, we show that there is functional redundancy between the two type II receptors as well as between the two type I receptors and that all four type II/type I receptor combinations are utilized in vivo. Targeting signaling specifically in myofibers also led to reductions in overall body fat content and improved glucose metabolism in mice fed either regular chow or a high-fat diet, demonstrating that these metabolic effects are the result of enhanced muscling. We observed no effect, however, on either bone density or muscle regeneration in mice in which signaling was targeted in myofibers. The latter finding implies that MSTN likely signals to other cells, such as satellite cells, in addition to myofibers to regulate muscle homeostasis.Domain walls, commonly occurring at the interface of different phases in solid-state materials, have recently been harnessed at the structural scale to enable additional modes of functionality. Here, we combine experimental, numerical, and theoretical tools to investigate the domain walls emerging upon uniaxial compression in a mechanical metamaterial based on the rotating-squares mechanism. We first show that these interfaces can be generated and controlled by carefully arranging a few phase-inducing defects. https://www.selleckchem.com/products/pentetic-acid.html We establish an analytical model to capture the evolution of the domain walls as a function of the applied deformation. We then employ this model as a guideline to realize interfaces of complex shape. Finally, we show that the engineered domain walls modify the global response of the metamaterial and can be effectively exploited to tune its stiffness as well as to guide the propagation of elastic waves.
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