Treg-specific deletion of the phosphatase SHP-1 impairs control of inflammation in vivo

INTRODUCTION: To achieve a healthy and functional immune system, a delicate balance exists between the activation of conventional T cells (Tcon cells) and the suppression by regulatory T cells (Treg). The tyrosine phosphatase SHP-1, a negative regulator of TCR signaling, shapes this \u27activation-suppression\u27 balance by modulating Tcon cell resistance to Treg-mediated suppression. Treg cells also express SHP-1, but its role in influencing Treg function is still not fully understood. METHODS: We generated a Treg-specific SHP-1 deletion model, RESULTS: We show that SHP-1 modulates Treg suppressive function at different levels. First, at the intracellular signaling level in Treg cells, SHP-1 attenuates TCR-dependent Akt phosphorylation, with loss of SHP-1 driving Treg cells towards a glycolysis pathway. At the functional level, SHP-1 expression limits the CONCLUSION: Our data identify SHP-1 as an important intracellular mediator for fine-tuning the balance between Treg-mediated suppression and Tcon activation/resistance

Methodologies for Improving HDR Efficiency

Clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) is a precise genome manipulating technology that can be programmed to induce double-strand break (DSB) in the genome wherever needed. After nuclease cleavage, DSBs can be repaired by non-homologous end joining (NHEJ) or homology-directed repair (HDR) pathway. For producing targeted gene knock-in or other specific mutations, DSBs should be repaired by the HDR pathway. While NHEJ can cause various length insertions/deletion mutations (indels), which can lead the targeted gene to lose its function by shifting the open reading frame (ORF). Furthermore, HDR has low efficiency compared with the NHEJ pathway. In order to modify the gene precisely, numerous methods arose by inhibiting NHEJ or enhancing HDR, such as chemical modulation, synchronized expression, and overlapping homology arm. Here we focus on the efficiency and other considerations of these methodologies

Study on Morph-genetic Materials Derived from Natural Materials

The way to fabricate novel morph-genetic functional materials based on nature bio-structures is reviewed. We present the idea and methods of obtaining multi-scale porous materials by using wood, agricultural wastes and butterfly wing scales as bio-templates

Determination of the number of ψ(3686)\psi(3686) events at BESIII

The numbers of ψ(3686) events accumulated by the BESIII detector for the data taken during 2009 and 2012 are determined to be and , respectively, by counting inclusive hadronic events, where the uncertainties are systematic and the statistical uncertainties are negligible. The number of events for the sample taken in 2009 is consistent with that of the previous measurement. The total number of ψ(3686) events for the two data taking periods is

Evidence of a resonant structure in the e+e−→π+D0D∗−e^+e^-\to \pi^+D^0D^{*-} cross section between 4.05 and 4.60 GeV

The cross section of the process e+e-→π+D0D*- for center-of-mass energies from 4.05 to 4.60 GeV is measured precisely using data samples collected with the BESIII detector operating at the BEPCII storage ring. Two enhancements are clearly visible in the cross section around 4.23 and 4.40 GeV. Using several models to describe the dressed cross section yields stable parameters for the first enhancement, which has a mass of 4228.6±4.1±6.3  MeV/c2 and a width of 77.0±6.8±6.3  MeV, where the first uncertainties are statistical and the second ones are systematic. Our resonant mass is consistent with previous observations of the Y(4220) state and the theoretical prediction of a DD¯1(2420) molecule. This result is the first observation of Y(4220) associated with an open-charm final state. Fits with three resonance functions with additional Y(4260), Y(4320), Y(4360), ψ(4415), or a new resonance do not show significant contributions from either of these resonances. The second enhancement is not from a single known resonance. It could contain contributions from ψ(4415) and other resonances, and a detailed amplitude analysis is required to better understand this enhancement