Ribosomopathies encompass a spectrum of disorders arising from impaired ribosome biogenesis and reduced functionality.Mutation or dysexpression of the genes that disturb any finely regulated steps of ribosome biogenesis can result in different types of ribosomopathies in clinic,collectively known as ribosomopathy genes.Emerging data suggest that ribosomopathy patients exhibit a significantly heightened susceptibility to cancer.Abnormal ribosome biogenesis and dysregulation of some ribo-somopathy genes have also been found to be intimately associated with cancer development.The cor-relation between ribosome biogenesis or ribosomopathy and the development of malignancies has been well established.This work aims to review the recent advances in the research of ribosomopathy genes among human cancers and meanwhile,to excavate the potential role of these genes,which have not or rarely been reported in cancer,in the disease development across cancers.We plan to establish a theoretical framework between the ribosomopathy gene and cancer development,to further facilitate the potential of these genes as diagnostic biomarker as well as pharmaceutical targets for cancer treatment.

Proteins usually associate with other molecules physically to execute their functions. Identifying these interactions is important for the functional analysis of proteins. Previously, we reported the parallel analysis of translated ORFs (PLATO) to couple ribosome display of full-length ORFs with affinity enrichment of mRNA/protein/ribosome complexes for the "bait" molecules, followed by the deep sequencing analysis of mRNA. However, the sample processing, from extraction of precipitated mRNA to generation of DNA libraries, includes numerous steps, which is tedious and may cause the loss of materials. Barcoded PLATO (PLATO-BC), an improved platform was further developed to test its application for protein interaction discovery. In this report, we tested the antisera-antigen interaction using serum samples from patients with inclusion body myositis (IBM). Tripartite motif containing 21 (TRIM21) was identified as a potentially new IBM autoantigen. We also expanded the application of PLATO-BC to identify protein interactions for JQ1, single ubiquitin peptide, and NS5 protein of Zika virus. From PLATO-BC analyses, we identified new protein interactions for these "bait" molecules. We demonstrate that Ewing sarcoma breakpoint region 1 (EWSR1) binds to JQ1 and their interactions may interrupt the EWSR1 association with acetylated histone H4. RIO kinase 3 (RIOK3), a newly identified ubiquitin-binding protein, is preferentially associated with K63-ubiquitin chain. We also find that Zika NS5 protein interacts with two previously unreported host proteins, par-3 family cell polarity regulator (PARD3) and chromosome 19 open reading frame 53 (C19orf53), whose attenuated expression benefits the replication of Zika virus. These results further demonstrate that PLATO-BC is capable of identifying novel protein interactions for various types of "bait" molecules.

BACKGROUND/AIMS: For patients with ankylosing spondylitis (AS), golimumab has consistent efficacy in controlling disease activity over 5 years but its benefit in preventing radiographic progression was less clear at 4 years. To predict radiographic progression, we analyzed the baseline characteristics of AS patients in a Korean population. METHODS: Sixty-eight Korean patients with AS participated in the phase 3, multicenter, randomized, placebo-controlled, double-blind trial (GO-RAISE) which has previously been described. Baseline modified stoke AS spine score (mSASSS) and change in mSASSS from baseline (ΔmSASSS) until week 208 were analyzed in the Korean patients enrolled in the GO-RAISE study. RESULTS: Although Korean patients had lower baseline mSASSS compared to non-Korean patients and received active management, radiographic progression was not prevented. Korean patients who did not undergo radiographic progression of spinal lesions of AS were younger and had shorter symptomatic duration, lower Bath AS functional and metrology indices, better chest expansion, and lower baseline mSASSS. The baseline mSASSS and ΔmSASSS were positively correlated in Korean AS patients (p < 0.001). Radiographic progression was more prevalent (80.0%) when baseline mSASSS > 10 and less common (13.0%) with baseline mSASSS = 0. CONCLUSIONS: In Korean AS patients, radiographic progression of the spine after 4 years was predicted effectively by the initial severity of the spinal lesion(s) in patients treated with golimumab.
Baths ; Disease Progression ; Humans ; Spine ; Spondylitis, Ankylosing* ; Thorax

As a dioxygenase, Ten-Eleven Translocation 2 (TET2) catalyzes subsequent steps of 5-methylcytosine (5mC) oxidation. TET2 plays a critical role in the self-renewal, proliferation, and differentiation of hematopoietic stem cells, but its impact on mature hematopoietic cells is not well-characterized. Here we show that Tet2 plays an essential role in osteoclastogenesis. Deletion of Tet2 impairs the differentiation of osteoclast precursor cells (macrophages) and their maturation into bone-resorbing osteoclasts in vitro. Furthermore, Tet2 mice exhibit mild osteopetrosis, accompanied by decreased number of osteoclasts in vivo. Tet2 loss in macrophages results in the altered expression of a set of genes implicated in osteoclast differentiation, such as Cebpa, Mafb, and Nfkbiz. Tet2 deletion also leads to a genome-wide alteration in the level of 5-hydroxymethylcytosine (5hmC) and altered expression of a specific subset of macrophage genes associated with osteoclast differentiation. Furthermore, Tet2 interacts with Runx1 and negatively modulates its transcriptional activity. Our studies demonstrate a novel molecular mechanism controlling osteoclast differentiation and function by Tet2, that is, through interactions with Runx1 and the maintenance of genomic 5hmC. Targeting Tet2 and its pathway could be a potential therapeutic strategy for the prevention and treatment of abnormal bone mass caused by the deregulation of osteoclast activities.
5-Methylcytosine ; analogs & derivatives ; chemistry ; metabolism ; Animals ; Cell Differentiation ; Cells, Cultured ; Core Binding Factor Alpha 2 Subunit ; genetics ; metabolism ; DNA-Binding Proteins ; physiology ; Genome ; Genomics ; Mice ; Mice, Knockout ; Osteoclasts ; cytology ; metabolism ; Proto-Oncogene Proteins ; physiology

An international brainstorming session on standardizing pattern identification (PI) was held at the Korea Institute of Oriental Medicine on October 1, 2013 in Daejeon, South Korea. This brainstorming session was convened to gather insights from international traditional East Asian medicine specialists regarding PI standardization. With eight presentations and discussion sessions, the meeting allowed participants to discuss research methods and diagnostic systems used in traditional medicine for PI. One speaker presented a talk titled "The diagnostic criteria for blood stasis syndrome: implications for standardization of PI". Four speakers presented on future strategies and objective measurement tools that could be used in PI research. Later, participants shared information and methodology for accurate diagnosis and PI. They also discussed the necessity for standardizing PI and methods for international collaborations in pattern research.
Internationality ; Medicine, Chinese Traditional ; standards ; Reference Standards ; Research

OBJECTIVERetrospectively analyzing post-transplant primary biliary cirrhosis patients to document the actual survival time, the cause of post-transplant death, and recurrences after liver transplantation in patients followed up by the Queensland Liver Transplant Service (QLTS).

METHODSThe case notes of all post-piggyback liver transplantation patients followed up by QLTS were reviewed. We analyzed the clinical characteristics of the PBC patients, post-transplant actual survival rates, the causes of post-transplant death, and risk factors of recurrence, and compared the survival rates between patients with and without liver transplantation using a European model.

RESULTSFifty-two post-transplant patients with 54 transplantations were identified with an average age of 53 years and a mean follow-up time of 55 months. The actual survival times of PBC patients with grafts for 1 years, 5 years and 10 years were 88.4%, 80.1%, 76.9% and 80.9%, 65.4%, 19.8%. The causes of death were MOF intra-abdominal bleeding, renal failure, sepsis and cardiovascular diseases. Comparing the survival rates between with and without transplantation, 8.5% of PBC patients have recurrences with an average recurrent time of 34 months.

CONCLUSION(1) Liver transplantation could improve survival rates, but the optimum time for transplantation should be focused on; (2) A long-term and larger follow-up sampling should be done to understand the effects of recurrences on patient's long-term survival; (3) CsA may play a more important role in preventing recurrence of PBC than Tacrolimus

Cyclosporine ; therapeutic use ; Female ; Follow-Up Studies ; Graft Rejection ; prevention & control ; Humans ; Liver Cirrhosis, Biliary ; surgery ; Liver Transplantation ; mortality ; Male ; Middle Aged ; Postoperative Period ; Retrospective Studies ; Secondary Prevention ; Survival Rate ; Treatment Outcome

Objective The in situ hybridization method was used with signal amplification system for detecting G-protein expression in taste buds. Methods The gene of gustducin and ?- rod transducin in rat are cloned by RT- PCR. Their sense and antisense probes were labeled with digoxigenin. About 150 taste buds in rat vallate and foliate papillae were analyzed. Results The results showed that there were 1.2 transducin-positive cells and 6.2 gustducin-positive cells counted in each taste bud profile on average. The number of gustduin-positive cells was approximately five times more than transducin-positive cells in taste buds. There were 4. 1% gustducin-positive cells and 0.8% transducin-positive cells in all taste cells. It could not be seen any cross reation of transducin probe to gustducin target. The high expression of transducin in retina was also observed but no gustducin expression could be detected. Conclusion The result of present study proved that both transducin and gustducin were taste G-protein and gustducin was high expressed. Both of them might be involved in taste signal transduction.