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  • Articles  (10)
  • 2015-2019  (5)
  • 2010-2014  (5)
  • Natural Sciences in General  (6)
  • Chemistry and Pharmacology  (5)
  • 1
    Publication Date: 2012-01-18
    Description: The type III histone deacetylase sirtuin 1 (Sirt1) is a suppressor of both innate and adoptive immune responses. We have recently found that Sirt1 expression is highly induced in anergic T cells. However, the transcriptional program to regulate Sirt1 expression in T cells remains uncharacterized. Here we report that the early responsive genes 2 and 3, which can be up-regulated by T-cell receptor-mediated activation of nuclear factor of activated T-cell transcription factors and are involved in peripheral T-cell tolerance, bind to the sirt1 promoter to transcript sirt1 mRNA. In addition, the forkhead transcription factor, FoxO3a, interacts with early responsive genes 2/3 on the sirt1 promoter to synergistically regulate Sirt1 expression. Interestingly, IL-2, a cytokine that can reverse T-cell anergy, suppresses sirt1 transcription by sequestering FoxO3a to the cytoplasm through activating the PI3K-AKT pathway. Expression of the constitutively active form of FoxO3a blocks IL-2–mediated reversal of T-cell tolerance by retaining sirt1 expression. Our findings here provide a molecular explanation of IL-2–mediated reversion of T-cell anergy.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 2
    Publication Date: 2013-11-13
    Description: We have developed electroosmotic pumps (EOPs) fabricated from 15-nm-thick porous nanocrystalline silicon (pnc-Si) membranes. Ultrathin pnc-Si membranes enable high electroosmotic flow per unit voltage. We demonstrate that electroosmosis theory compares well with the observed pnc-Si flow rates. We attribute the high flow rates to high electrical fields present across the...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 3
    Publication Date: 2016-09-14
    Description: Humoral immunity involves multiple checkpoints during B-cell development, maturation, and activation. The cell death receptor CD95/Fas-mediated apoptosis plays a critical role in eliminating the unwanted activation of B cells by self-reactive antigens and in maintaining B-cell homeostasis through activation-induced B-cell death (AICD). The molecular mechanisms controlling AICD remain largely undefined....
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 4
    Publication Date: 2016-10-29
    Description: Bacterial endotoxin can induce inflammatory and metabolic changes in the host. In this study, we revealed a molecular mechanism by which a stress-inducible, liver-enriched transcription factor, cAMP-responsive element-binding protein hepatic-specific (CREBH), modulates lipid profiles to protect the liver from injuries upon the bacterial endotoxin lipopolysaccharide (LPS). LPS challenge can activate CREBH in mouse liver tissues in a toll-like receptor (TLR)/MyD88-dependent manner. Upon LPS challenge, CREBH interacts with TNF receptor-associated factor 6 (TRAF6), an E3 ubiquitin ligase that functions as a key mediator of TLR signaling, and this interaction relies on MyD88. Further analysis demonstrated that TRAF6 mediates K63-linked ubiquitination of CREBH to facilitate CREBH cleavage and activation. CREBH directly activates expression of the gene encoding Apolipoprotein A4 (ApoA4) under LPS challenge, leading to modulation of high-density lipoprotein (HDL) in animals. CREBH deficiency led to reduced production of circulating HDL and increased liver damage upon high-dose LPS challenge. Therefore, TLR/MyD88-dependent, TRAF6-facilitated CREBH activation represents a mammalian hepatic defense response to bacterial endotoxin by modulating HDL.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
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  • 5
    Publication Date: 2017-07-28
    Description: Afferent specific role of NMDA receptors for the circuit integration of hippocampal neurogliaform cells Nature Communications, Published online: 28 July 2017; doi:10.1038/s41467-017-00218-y Proper brain function depends on the correct assembly of excitatory and inhibitory neurons into neural circuits. Here the authors show that during early postnatal development in mice, NMDAR signaling via activity of long-range synaptic inputs onto neurogliaform cells is required for their appropriate integration into the hippocampal circuitry.
    Electronic ISSN: 2041-1723
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics
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  • 6
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2017-04-29
    Description: Origami structures are of great interest in microelectronics, soft actuators, mechanical metamaterials, and biomedical devices. Current methods of fabricating origami structures still have several limitations, such as complex material systems or tedious processing steps. We present a simple approach for creating three-dimensional (3D) origami structures by the frontal photopolymerization method, which can be easily implemented by using a commercial projector. The concept of our method is based on the volume shrinkage during photopolymerization. By adding photoabsorbers into the polymer resin, an attenuated light field is created and leads to a nonuniform curing along the thickness direction. The layer directly exposed to light cures faster than the next layer; this nonuniform curing degree leads to nonuniform curing–induced volume shrinkage. This further introduces a nonuniform stress field, which drives the film to bend toward the newly formed side. The degree of bending can be controlled by adjusting the gray scale and the irradiation time, an easy approach for creating origami structures. The behavior is examined both experimentally and theoretically. Two methods are also proposed to create different types of 3D origami structures.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 7
    Publication Date: 2018-06-09
    Description: Soft adaptable materials that change their shapes, volumes, and properties in response to changes under ambient conditions have important applications in tissue engineering, soft robotics, biosensing, and flexible displays. Upon water absorption, most existing soft materials, such as hydrogels, show a positive volume change, corresponding to a positive swelling. By contrast, the negative swelling represents a relatively unusual phenomenon that does not exist in most natural materials. The development of material systems capable of large or anisotropic negative swelling remains a challenge. We combine analytic modeling, finite element analyses, and experiments to design a type of soft mechanical metamaterials that can achieve large effective negative swelling ratios and tunable stress-strain curves, with desired isotropic/anisotropic features. This material system exploits horseshoe-shaped composite microstructures of hydrogel and passive materials as the building blocks, which extend into a periodic network, following the lattice constructions. The building block structure leverages a sandwiched configuration to convert the hydraulic swelling deformations of hydrogel into bending deformations, thereby resulting in an effective shrinkage (up to around –47% linear strain) of the entire network. By introducing spatially heterogeneous designs, we demonstrated a range of unusual, anisotropic swelling responses, including those with expansion in one direction and, simultaneously, shrinkage along the perpendicular direction. The design approach, as validated by experiments, allows the determination of tailored microstructure geometries to yield desired length/area changes. These design concepts expand the capabilities of existing soft materials and hold promising potential for applications in a diverse range of areas.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 8
    Publication Date: 2013-11-16
    Description: The inositol-requiring enzyme 1α (IRE1α) is a serine-threonine kinase that plays crucial roles in activating the unfolded protein response. Studies suggest that IRE1α is activated during thymic T cell development and in effector CD8+ T cells. However, its role in regulating T helper cell differentiation remains unknown. We find that IRE1α is up-regulated and activated upon CD4+ T cell activation and plays an important role in promoting cytokine IL-4 production. CD4+ T cells from IRE1α KO mice have reduced IL-4 protein expression, and this impaired IL-4 production is not due to the altered expression of Th2 lineage-specific transcription factors, such as GATA3. Instead, IL-4 mRNA stability is reduced in IRE1α KO T cells. Furthermore, treatment of T cells with an IRE1α-specific inhibitor, 4μ8C, leads to a block in IL-4, IL-5, and IL-13 production, confirming the role of IRE1α in the regulation of IL-4. This study identifies a regulatory function for IRE1α in the promotion of IL-4 in T cells.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
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  • 9
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    The American Society for Biochemistry and Molecular Biology (ASBMB)
    Publication Date: 2013-12-28
    Description: The type III histone deacetylase Sirt1 has recently emerged as a critical immune regulator by suppressing T cell immunity and macrophage activation during inflammation, but its role in dendritic cells (DCs) remains unknown. Here, we show that mice with genetic Sirt1 deletion specifically in DCs are resistant to MOG-induced experimental autoimmune encephalomyelitis. Loss of Sirt1 functions in DCs enhances their ability to produce IL-27 and interferon β (IFN-β). Co-cultivation of Sirt1-null DCs with CD4+ T cells inhibited Th17 differentiation, which is reversed by anti-IL27 and anti-IFN-β neutralization antibodies. Sirt1 antagonizes acetylation of IRF1, a transcription factor that drives IL-27 production. Genetic deletion of IRF1 in Sirt1-null DCs abolishes IL-27 production and suppresses Th17 differentiation. Our results show that the histone deacetylase Sirt1 programs DCs to regulate Th17 differentiation during inflammation.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
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  • 10
    Publication Date: 2014-02-01
    Description: Magnesium is widely used to control calcium carbonate deposition in the shell of pearl oysters. Matrix proteins in the shell are responsible for nucleation and growth of calcium carbonate crystals. However, there is no direct evidence supporting a connection between matrix proteins and magnesium. Here, we identified a novel acidic matrix protein named PfN44 that affected aragonite formation in the shell of the pearl oyster Pinctada fucata. Using immunogold labeling assays, we found PfN44 in both the nacreous and prismatic layers. In shell repair, PfN44 was repressed, whereas other matrix proteins were up-regulated. Disturbing the function of PfN44 by RNAi led to the deposition of porous nacreous tablets with overgrowth of crystals in the nacreous layer. By in vitro circular dichroism spectra and fluorescence quenching, we found that PfN44 bound to both calcium and magnesium with a stronger affinity for magnesium. During in vitro calcium carbonate crystallization and calcification of amorphous calcium carbonate, PfN44 regulated the magnesium content of crystalline carbonate polymorphs and stabilized magnesium calcite to inhibit aragonite deposition. Taken together, our results suggested that by stabilizing magnesium calcite to inhibit aragonite deposition, PfN44 participated in P. fucata shell formation. These observations extend our understanding of the connections between matrix proteins and magnesium.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
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