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MYO5A is a major actin-based vesicle transport motor that binds to one of its cargos, the melanosome, by means of a RAB27A/MLPH receptor. When one of the members of this receptor-motor complex is mutated, the melanosomes clump in the perinuclear region of the melanocyte and are transferred unevenly to the developing hair, leading to a dilution of coat color. Mutation of a fourth gene, dilute suppressor (dsu), suppresses this coat color dilution. MYO5A is required for the peripheral accumulation of melanosomes in melanocytes, but its role in melanosome transfer to neighboring keratinocytes and the hair is unknown. Here, we show that MYO5A is nonessential for melanosome transfer, although pigment incorporation into the hair in MYO5A-deficient mice is uneven, probably due to the clumping of melanosomes that occurs in the perinuclear region of mutant melanocytes. We also show that dsu is caused by a loss-of-function mutation in a unique vertebrate-specific protein that appears to function in an MYO5A-independent pathway to alter pigment incorporation into the hair. Therefore, dsu identifies a unique protein involved in pigmentation of the mammalian hair.

Casein kinase 2 （CK2） is a highly pleiotropic serine-threonine kinase, which catalyzed phosphorylation of more than 300 proteins that are implicated in regulation of many cellular functions, such as signal transduction, transcriptional control, apoptosis and the cell cycle. On the other hand, CK2 is abnormally elevated in a variety of tumors, and is considered as a promising therapeutic target. The currently available ATP-competitive CK2 inhibitors, however, lack selectivity, which has impeded their development in cancer therapy. Because allosteric inhibitors can avoid the shortcomings of conventional kinase inhibitors, this study was aimed to discover a new allosteric site in CK2α and to investigate the effects of mutations in this site on the activity of CK2α. Using AIIosite based on protein dynamics and structural alignment, we predicted a new allosteric site that was partly located in the αC helix of CK2α. Five residues exposed on the surface of this site were mutated to validate the prediction. Kinetic analyses were performed using a luminescent ADP detection assay by varying the concentrations of a peptide substrate, and the results showed that the mutations 178C and 178W decreased CK2α activity, whereas V31R, K75E, 182C and P109C increased CK2α activity. Potential allosteric pathways were identified using the Monte Carlo path generation approach, and the results of these predicted allosteric pathways were consistent with the mutation analysis. Multiple sequence alignments of CK2a with the other kinases in the family were conducted using the ClustaIX method, which revealed the diversity of the residues in the site. In conclusion, we identified a new allosteric site in CK2α that can be altered to modulate the activity of the kinase. Because of the high diversity of the residues in the site, the site can be targeted using rational drug design of specific CK2α inhibitors for biological relevance.

As they are products of glacier movement, the water body composition and water quality attributes of glacial lakes have distinct characteristics compared with inland lakes. Although satellite remote sensing provides an effective approach to monitor water quality, lack of in-situ measurement data on the status and environment surrounding glacial lakes presents a major constraint in relating satellite data to water quality indicators. This study presents findings of a preliminary investigation into water quality attributes of 3 glacial lakes in the Mount Qomolangma region. Suspended particulate matter （SPM）, light absorption attributes of phytoplankton, nonalgal particles （NAP）, and colored dissolved organic matter （CDOM） were measured. The suspended substance concentration varies markedly from 0-320 mg/L. This is considered to reflect differing stages of lake development. l-he chlorophyll concentra- tion is much lower than that found for inland lakes, as landscapes that surround these high altitude lakes have almost no vegetation growth. The phytoplankton and CDOM concentration depend on long-term stability of lake slopes. Given the lack of exogenous and endogenous inputs in the Qomolangma region, CDOM in glacial lakes is significantly lower than in inland lakes. These preliminary findings could support efforts to appraise estimates of water quality parameters using remotely sensed images.

Treatment for optic nerve injury by brain-derived neurotrophic factor or the transplantation of human umbilical cord blood stem cells has gained progress, but analysis by biomechanical indicators is rare. Rabbit models of optic nerve injury were established by a clamp. At 7 days after injury, the vitreous body received a one-time injection of 50 μg brain-derived neurotrophic factor or 1 × 10^6 human umbilical cord blood stem cells. After 30 days, the maximum load, maximum stress, maximum strain, elastic limit load, elastic limit stress, and elastic limit strain had clearly improved in rabbit models of optical nerve injury after treatment with brain-derived neurotrophic factor or human umbilical cord blood stem cells. The damage to the ultrastructure of the optic nerve had also been reduced. These findings suggest that human umbilical cord blood stem cells and brain-derived neurotrophic factor effectively repair the injured optical nerve, improve biomechanical properties, and contribute to the recovery after injury.

A parameter perturbation for the unsteady-state heat-transfer characteristics of honeycomb regenerator is presented. It is limited to the cases where the storage matrix has a small wall thickness so that no temperature variation in the matrix perpendicular to the flow direction is considered. Starting from a two-phase transient thermal model for the gas and storage matrix, an approximate solution for regenerator heat transfer process is derived using the multiple-scale method for the limiting case where the longitudinal heat conduction of solid matrix is far less than the convective heat transfer between the gas and the solid. The regenerator temperature profiles are expressed as Taylor series of the coefficient of solid heat conduction item in the model. The analytical validity is shown by comparing the perturbation solution with the experiment and the numerical solution. The results show that it is possible for the perturbation to improve the effectiveness and economics of thermal research on regenerators.

Objective: To retrospectively evaluate appropriate treatment for patients with symptomatic caliceal diverticular calculi, by comparing the therapeutic outcomes for those undergoing minimally invasive percutaneous nephrolithotomy (MPCNL) and flexible ureterorenoscopy (F-URS). Methods: From March 2009 to May 2014, 36 consecutive patients with caliceal diverticular calculi were divided into 2 groups:21 patients underwent MPCNL, and 15 were treated by F-URS. All procedures were performed by one surgical group, which ensured relatively constant parameters. Patient characteristics, operative time, hospital stay after surgery, stone-free rate, symptomatic improvement rate, complications, diverticular obliteration, and stone composition were analyzed retrospectively in the 2 groups. Results: Patient preoperative variables were comparable between the two groups, with no significant difference (P>0.05). Mean operative time was 136.9 ± 22.8 min in the MPCNL group and 117.3 ± 24.3 min in the F-URS group (P ? 0.019). Hospital stay was significantly longer in the MPCNL group than in the F-URS group (9.4 ± 3.1 vs. 6.9 ± 2.1 days, P ? 0.010). The stone-free rates after MPCNL and F-URS were 90.5%(19/21) and 60.0%(9/15), respectively (P ? 0.046). Additionally, 71.4%(15/21) of patients in the MPCNL group and 46.7%(7/15) of patients in the F-URS group had symptomatic improvement at the 6-month follow-up (P ? 0.175);the rates of complications in the 2 groups were 19.0%(4/21) and 13.3%(2/15), respectively (P ? 0.650). Complete diverticular obliteration was achieved in 16 (76.2%) cases in the MPCNL group and 5 (33.3%) cases in the F-URS group (P ? 0.017). The distributions of calcium oxalate and hydroxyapatite in the stones were 66.7% (14/21) and 33.3% (7/21), respectively, in the MPCNL group;however, the distributions in the F-URS group were 46.7%(7/15) and 53.3%(8/15), respec-tively (P ? 0.310). Conclusion: MPCNL is an effective method for the treatment of caliceal diverticular calculi. However, F-URS is an alternative technique in selected patients with a patent infundibulum, despite lower stone-free rates than with MPCNL. Fulguration of the diverticular lining with a high-power holmium laser and permitting the cavity to collapse are useful to increase the chance of diverticular obliteration.

Objective： To compare biliary complications after biliary tract reconstruction with or without T-tube in orthotopic liver transplantation. Methods： Randomized control trials （RCTs） and comparative studies were identified by a computerized literature search of the Cochrane Library, MEDLINE （1966/1-2010/4）, Scopus （1980/1-2010/4）, ClinicalTrials.gov （2010/4）, the Cochrane Hepato-Biliary Group Controlled Trials Register, and the Cochrane Central Register of Controlled Trials. Studies and data were extracted and assessed independently. Dichotomous outcomes were reported as odds ratios （ORs） and weighted mean difference with 95% confidence intervals （CI）. Results： Five RCTs and eight comparative studies with a total of 1 608 subjects were identified. The data showed that the operation with T-tube had better outcomes for duct stenosis （P=0.01, OR=0.45, 95% CI 0.24-0.85）. The operations with or without T-tube had equivalent outcomes as follows： overall biliary complications （P=0.85, OR=I. 15, 95% CI 0.28-4.72） bile leaks （P=0.38, OR=0.75, 95% CI 0.39-1.42）, and cholangitis （P=0.24, OR=4.64, 95% CI 0.36-60.62）. These results were strengthened by the analysis of all thirteen non-randomized and randomized studies. Conclusions： Our systematic review and meta-analysis suggest that the insertion of a T-tube reduces the incidence of biliary stenosis without increasing the incidence of other biliary complications.

Single atoms of platinum group metals on CeO 2 represent a potential approach to lower precious metal requirements for automobile exhaust treatment catalysts. Here we show the dynamic evolution of two types of single-atom Pt (Pt 1 ) on CeO 2 , i.e., adsorbed Pt 1 in Pt/CeO 2 and square planar Pt 1 in Pt AT CeO 2 , fabricated at 500 °C and by atom-trapping method at 800 °C, respectively. Adsorbed Pt 1 in Pt/CeO 2 is mobile with the in situ formation of few-atom Pt clusters during CO oxidation, contributing to high reactivity with near-zero reaction order in CO. In contrast, square planar Pt 1 in Pt AT CeO 2 is strongly anchored to the support during CO oxidation leading to relatively low reactivity with a positive reaction order in CO. Reduction of both Pt/CeO 2 and Pt AT CeO 2 in CO transforms Pt 1 to Pt nanoparticles. However, both catalysts retain the memory of their initial Pt 1 state after reoxidative treatments, which illustrates the importance of the initial single-atom structure in practical applications. The use of single atoms of platinum group metals on CeO 2 is a promising approach to reduce precious metal requirements for automobile exhaust treatment catalysts. Here, the authors discovered that by manipulating the calcination temperatures, they could control the configuration of Pt1 on the CeO 2 surface, leading to differences in CO oxidation activity.

To survive under adverse conditions, plants form stress granules (SGs) to temporally store mRNA and halt translation as a primary response. Dysregulation in SG disassembly can have detrimental effects on plant survival after stress release, yet the underlying mechanism remains poorly understood. Using Arabidopsis as a model system, we demonstrate that the β subunit of adaptor protein (AP) -3 complex (AP-3β) interacts with the SG core RNA-binding proteins Tudor staphylococcal nuclease 1/2 (TSN1/2) both in vitro and in vivo. We also show that AP-3β is rapidly recruited to SGs upon heat induction and plays a key role in disassembling SGs during stress recovery. Genetic evidences support that AP-3β serves as an adaptor to recruit the 19S regulatory particle (RP) of the proteasome to SGs. Notably, the 19S RP promotes SG disassembly through RP-associated deubiquitylation, independent of its proteolytic activity. This deubiquitylation process of SG components is crucial for translation reinitiation and growth recovery after heat release. Our findings uncover a previously unexplored role of the 19S RP in regulating SG disassembly and highlights the importance of endomembrane proteins in supporting RNA granule dynamics in plants. This study demonstrates that the adaptor protein AP-3β recruits the 19S regulatory particle (RP) of the proteasome to stress granules (SGs) after heat stress and promotes SG disassembly through RP-associated deubiquitylation process.

Background Osteoarthritis (OA) is the most common articular disorder, leading to joint malfunction and disability. Although the incidence of OA is increasing globally, the treatment of OA is very limited. LncRNA CIR has been implicated in OA through unclear mechanisms. Here, we investigated the role of lncRNA CIR in chondrogenic differentiation. Methods Human umbilical-cord-derived mesenchymal stem cells (hUC-MSCs) were obtained from human umbilical cords. Flow cytometry was used to analyze the surface markers of hUC-MSCs. Various culture conditions and corresponding staining assays were employed to assess the differentiation abilities of hUC-MSC. qRT-PCR, western blot, and immunostaining were used to measure expression levels of related genes and proteins such as lncRNA CIR, ATOH8, EZH2, and H3K27me3. RNA immunoprecipitation assay, biotin pull-down, and chromatin immunoprecipitaion assay were performed to analyze the interactions of lncRNA CIR, EZH2, H3K27me3 and ATOH8 promoter. Results hUC-MSCs exhibited MSCs features and could differentiate into chondrocytes under specific conditions. LncRNA CIR was downregulated while ATOH8 was upregulated during the chondrogenic differentiation of hUC-MSCs. Knockdown lncRNA CIR or overexpression of ATOH8 promoted chondrogenic differentiation. Further, lncRNA CIR bound to EZH2 and repressed ATOH8 expression via EZH2-mediated H3K27me3, which promotes the methylation of ATOH8. Inhibition of ATOH8 reversed the effects of knockdown lncRNA CIR on chondrogenic differentiation. Conclusion LncRNA CIR suppresses chondrogenic differentiation of hUC-MSCs. Mechanistically, lncRNA CIR could inhibit ATOH8 expression that functions to promote chondrogenic differentiation through EZH2-mediated epigenetic modifications.