In rheumatoid arthritis (RA), macrophage is one of the major sources of inflammatory mediators. Macrophages produce inflammatory cytokines through toll‐like receptor (TLR)‐mediated signalling during RA. Herein, we studied macrophages from the synovial fluid of RA patients and observed a significant increase in activation of inositol‐requiring enzyme 1α (IRE1α), a primary unfolded protein response (UPR) transducer. Myeloid‐specific deletion of the IRE1α gene protected mice from inflammatory arthritis, and treatment with the IRE1α‐specific inhibitor 4U8C attenuated joint inflammation in mice. IRE1α was required for optimal production of pro‐inflammatory cytokines as evidenced by impaired TLR‐induced cytokine production in IRE1α‐null macrophages and neutrophils. Further analyses demonstrated that tumour necrosis factor (TNF) receptor‐associated factor 6 (TRAF6) plays a key role in TLR‐mediated IRE1α activation by catalysing IRE1α ubiquitination and blocking the recruitment of protein phosphatase 2A (PP2A), a phosphatase that inhibits IRE1α phosphorylation. In summary, we discovered a novel regulatory axis through TRAF6‐mediated IRE1α ubiquitination in regulating TLR‐induced IRE1α activation in pro‐inflammatory cytokine production, and demonstrated that IRE1α is a potential therapeutic target for inflammatory arthritis.

The reduced protein expression of SIRT6 tumor suppressor is involved in tumorigenesis. The molecular mechanisms underlying SIRT6 protein downregulation in human cancers remain unknown. Using a proteomic approach, we have identified the ubiquitin-specific peptidase USP10, another tumor suppressor, as one of the SIRT6-interacting proteins. USP10 suppresses SIRT6 ubiquitination to protect SIRT6 from proteasomal degradation. USP10 antagonizes the transcriptional activity of the c-Myc oncogene through SIRT6, as well as p53, to inhibit cell cycle progression, cancer cell growth, and tumor formation. To support this conclusion, we detected significant reductions in both USP10 and SIRT6 protein expression in human colon cancers. Our study discovered crosstalk between two tumor-suppressive genes in regulating cell cycle progression and proliferation and showed that dysregulated USP10 function promotes tumorigenesis through SIRT6 degradation.

Yang et al. demonstrate that Hrd1 plays an important role in DC induction of CD4 T cell immunity. The underlying mechanism involves the ability of Hrd1 to ubiquitinate and degrade BLIMP-1, thus releasing CIITA from transcriptional repression and promoting MHCII expression. As a consequence, Hrd1−/− DCs protect mice from MOG-induced experimental autoimmune encephalomyelitis.

The elevated level of CCNB1 indicates more aggressive cancer and poor prognosis. However, the factors that cause CCNB1 upregulation remain enigmatic. Herein, we identify USP22 as a CCNB1 interactor and discover that both USP22 and CCNB1 are dramatically elevated with a strong positive correlation in colon cancer tissues. USP22 stabilizes CCNB1 by antagonizing proteasome-mediated degradation in a cell cycle-specific manner. Phosphorylation of USP22 by CDK1 enhances its activity in deubiquitinating CCNB1. The ubiquitin ligase anaphase-promoting complex (APC/C) targets USP22 for degradation by using the substrate adapter CDC20 during cell exit from M phase, presumably allowing CCNB1 degradation. Finally, we discover that USP22 knockdown leads to slower cell growth and reduced tumor size. Our study demonstrates that USP22 is a CCNB1 deubiquitinase, suggesting that targeting USP22 might be an effective approach to treat cancers with elevated CCNB1 expression.

Herpes zoster (HZ) exists widely in China and most cases occur among old people, but no epidemiology information of HZ was available. We aimed to investigate the epidemiology characteristics of HZ among adults aged 50 and over in Guangdong, China. A total of 34 counties/districts were randomly selected in Guangdong, and 7149 residents aged 50 and over were investigated by local CDC professionals using accidental sampling method. There were 247 respondents having had HZ before; the lifetime prevalence of HZ among people aged 50 and above in study area was 3.46%. The prevalence in females was higher than that in males. Pearl River Delta had the highest prevalence (5.29%), while Northern Guangdong had the lowest (1.87%). The annual incidence in the year 2013, 2012 and 2011 was 5.8, 3.4 and 4.1 per 1000 person-years, respectively. Detailed investigation of HZ cases showed that all cases meted the definition of HZ and had at least 1 typical symptom. 40% cases had suffered post-herpetic neuralgia. 75.9% cases had sought aid from hospital and 9.1% of them had been hospitalized. People who sought aid from hospital had more serious level of neuralgia. The epidemiology features of HZ in Guangdong were consistent with the current findings in other countries. The results of this study can provide baseline epidemiology information of HZ for further studies.

Identification of positive regulators of T-cell immunity induced during autoimmune diseases is critical for developing novel therapies. The endoplasmic reticulum resident ubiquitin ligase Hrd1 has recently emerged as a critical regulator of dendritic cell antigen presentation, but its role in T-cell immunity is unknown. Here we show that genetic deletion of Hrd1 in mice inhibits T-cell proliferation, production of IL-2, and differentiation of Th1 and Th17 cells, and consequently protects mice from experimental autoimmune encephalomyelitis. Hrd1 facilitates T-cell proliferation by the destruction of cyclin-dependent kinase inhibitor p27kip1, and deletion of p27kip1 in Hrd1-null T-cells rescues proliferative capacity but not the production of cytokines, including IL-2, IFN-γ and IL-17. T-cell expression of Hrd1 is higher in patients with multiple sclerosis than in healthy individuals, and knockdown of Hrd1 in human CD4+ T cells inhibits activation and differentiation to Th1 and Th17 cells. Our study identifies Hrd1 as a previously unappreciated positive regulator of T cells and implies that Hrd1 is a potential therapeutic target for autoimmune diseases.

With the rapid rising of global population, the demand for improving breeding techniques to greatly increase the worldwide crop production has become more and more urgent. Most researchers believe that the key to new breeding techniques lies in genetic improvement of crops, which leads to a large quantity of phenotyping spots. Unfortunately, current phenotyping solutions are not powerful enough to handle so many spots with satisfying speed and accuracy. As a result, high-throughput phenotyping is drawing more and more attention. In this paper, we propose a new field-based sensing solution to high-throughput phenotyping. We mount a LiDAR (Velodyne HDL64-S3) on a mobile robot, making the robot a “phenomobile.” We develop software for data collection and analysis under Robotic Operating System using open source components and algorithm libraries. Different from conducting phenotyping observations with an in-row and one-by-one manner, our new solution allows the robot to move around the parcel to collect data. Thus, the 3D and 360° view laser scanner can collect phenotyping data for a large plant group at the same time, instead of one by one. Furthermore, no touching interference from the robot would be imposed onto the crops. We conduct experiments for maize plant on two parcels. We implement point cloud merging with landmarks and Iterative Closest Points to cut down the time consumption. We then recognize and compute the morphological phenotyping parameters (row spacing and plant height) of maize plant using depth-band histograms and horizontal point density. We analyze the cloud registration and merging performances, the row spacing detection accuracy, and the single plant height computation accuracy. Experimental results verify the feasibility of the proposed solution.

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