Efficient Demyristoylase Activity of SIRT2 Revealed by Kinetic and Structural Studies

published_or_final_versio

Lenalidomide regulates CNS autoimmunity by promoting M2 macrophages polarization

Multiple sclerosis (MS) is a chronic and debilitating neurological disorder of the central nervous system (CNS), characterized by infiltration of leukocytes into CNS and subsequent demyelination. Emerging evidences have revealed the beneficial roles of M2 macrophages in ameliorating experimental autoimmune encephalomyelitis (EAE), a model for MS. Here, we identify that lenalidomide alone could promote macrophages M2 polarization to prevent the progression of EAE, which is associated with subsequent inhibition of proinflammatory Th1 and Th17 cells both in peripheral lymph system and CNS. Depletion of macrophages by pharmacology treatment of clodronate liposomes or transferring lenalidomide-induced BMDMs in EAE mice completely abolished the therapeutic effect of lenalidomide or prevented EAE development, respectively. The macrophages-derived IL10 was upregulated both in vivo and in vitro after lenalidomide treatment. Moreover, lenalidomide-treated IL10-dificient EAE mice had higher clinical scores and more severe CNS damage, and intravenous injection of lenalidomide-treated IL10BMDMs into mice with EAE at disease onset did not reverse disease severity, implying IL10 may be essential in lenalidomide-ameliorated EAE. Mechanistically, lenalidomide significantly increased expression and autocrine secretion of IL10, subsequently activated STAT3-mediated expression of Ym1. These studies facilitate the development of potential novel therapeutic application of lenalidomide for the treatment of MS

Melanism patches up the defective cuticular morphological traits through promoting the up-regulation of cuticular protein-coding genes in Bombyx mori

Melanin and cuticular proteins are important cuticle components in insect. Cuticle defects caused by mutations in cuticular protein-encoding genes can hinder melanin deposition. However, the effects of melanin variation on cuticular protein-encoding genes and the corresponding morphological traits associated with these genes are remain largely unknown. Using Bombyx mori as a model, we showed that the melanism levels during larval cuticle pigmentation correlated positively with the expression of cuticular protein-encoding genes. This correlation stemmed from the simultaneous induction of these genes by the melanin precursors. More importantly, the effect of the melanism background on the cuticles induced the up-regulation of other functionally redundant cuticular protein-encoding genes to rescue the morphological and adaptive defects caused by the dysfunction of some mutated cuticular proteins, and the restorative ability increased with increasing melanism levels, which gives a novel evidence that melanism enhances insect adaptability. These findings deepen our understanding of the interactions among cuticle components, as well as their importance in the stabilizing of the normal morphology and function of the cuticle

Terahertz master-oscillator power-amplifier quantum cascade lasers

We report on the realization of a monolithically integrated master-oscillator power-amplifier architecture in a terahertz quantum cascade laser (THz-QCL) with a metal-metal waveguide. The master-oscillator section is a first-order distributed feedback (DFB) laser. Instead of using a thick anti-reflection coating, we exploit a diffraction grating together with an absorbing boundary in the power-amplifier section to efficiently extract the laser radiation and suppress the self-lasing in it. The devices demonstrate a stable generation and power amplification of single-mode emission. The amplification factor is about 5, and the output power is approximately twice that of the standard second-order DFB lasers fabricated from the same material. Emission beam pattern with a divergence angle of ∼18 × 40° is achieved. Our work provides an avenue for the realization of single-mode THz-QCLs with high output power and good beam quality