Influence of graphene on the electronic and magnetic properties of an iron(III) porphyrin chloride complex.

Although iron-based single atom catalysts are regarded as a promising alternative to precious metal catalysts, their precise electronic structures during catalysis still pose challenges for computational descriptions. A particularly urgent issue to be addressed is the influence of the environment on the electronic structure, and how to describe this accurately using computational methods. Here, we study an iron porphyrin chloride complex adsorbed on a graphene sheet using density functional theory calculations to probe how much the electronic structure is influenced by the presence of a graphene layer. Our results indicate that weak interactions due to van der Waals forces dominate between the porphyrin complex and graphene, and only a small amount of charge is transferred between the two entities. Furthermore, the interplay of the ligand field environment, strong p-d hybridization, and correlation effects within the complex are strongly involved in determining the spin state of the iron ion. By bridging molecular chemistry and solid state physics, this study provides first steps towards a joint analysis of the properties of iron-based catalysts from first principles.

The histone demethylase KDM4B interacts with MyoD to regulate myogenic differentiation in C2C12 myoblast cells.

Enzymes that mediate posttranslational modifications of histone and nonhistone proteins have been implicated in regulation of skeletal muscle differentiation. However, functions of histone demethylases that could counter the actions of H3-K9 specific histone methyltransferases remain still obscure. Here we present evidences that KDM4B histone demethylase regulates expression of myogenic regulators such as MyoD and thereby controls myogenic differentiation of C2C12 myoblast cells. We demonstrate that expression of KDM4B gradually increases during myogenic differentiation and depletion of KDM4B using shRNA results in inhibition of differentiation in C2C12 myoblast cells, which is correlated with decreased expression of MyoD and myogenin. In addition, we find that KDM4B shRNA represses expression of MyoD promoter-driven luciferase reporter and exogenous expression of MyoD rescues myogenic potential in KDM4B-depleted myoblast cells. We further show that KDM4B interacts with MyoD, binds to MyoD and myogenin promoters in vivo, and finally, is involved in demethylation of tri-methylated H3-K9 on promoters of MyoD and myogenin. Taken together, our data suggest that KDM4B plays key roles in myogenic differentiation of C2C12 cells, presumably by its function as a H3-K9 specific histone demethylase.

Arthroscopic debridement for acutely infected prosthetic knee: any role for infection control and prosthesis salvage?

PURPOSE: The purpose of this study was to assess the success rate of arthroscopic debridement guided by C-reactive protein (CRP) levels for acutely infected total knee prostheses. METHODS: From January 2002 to December 2009, 16 consecutive eligible patients met the following inclusion criteria: duration of symptoms less than 72 hours, previously well-functioning prostheses, and no radiographic signs of loosening. Each patient underwent arthroscopy with thorough debridement and synovectomy and copious irrigation. In addition to the standard anterior portals, a posterior portal was used, and a drain was placed through this portal. The need for subsequent open debridement was determined by the postarthroscopy trends of CRP levels. Treatment success was defined as continuing freedom from infection based on clinical and laboratory results, salvage of the prosthesis, and no evidence of infection for at least 2 years. RESULTS: Arthroscopic debridement eradicated the infection in 10 (62.5%) of the 16 cases. The other 6 knees (37.5%) underwent subsequent open debridement with polyethylene insert exchange, which resulted in successful infection control with prosthetic salvage. CONCLUSIONS: Patients who had undergone total knee arthroplasty (TKA) and had acute joint infection for less than 72 hours with no evidence of a loosening prosthesis were treated by arthroscopic debridement guided by the CRP level and had a 62.5% success rate with arthroscopic treatment alone but a 100% success rate when initial failures were treated with open debridement and polyethylene exchange. LEVEL OF EVIDENCE: Level IV, case series.

Crystal and Electronic Structure of Oxygen Vacancy Stabilized Rhombohedral Hafnium Oxide.

Hafnium oxide is an outstanding candidate for next-generation nonvolatile memory solutions such as OxRAM (oxide-based resistive memory) and FeRAM (ferroelectric random access memory). A key parameter for OxRAM is the controlled oxygen deficiency in HfO2-x which eventually is associated with structural changes. Here, we expand the view on the recently identified (semi-)conducting low-temperature pseudocubic phase of reduced hafnium oxide by further X-ray diffraction analysis and density functional theory (DFT) simulation and reveal its rhombohedral nature. By performing total energy and electronic structure calculations, we investigate phase stability and band structure modifications in the presence of oxygen vacancies. With increasing oxygen vacancy concentration, the material transforms from the well-known monoclinic structure to a (pseudocubic) polar rhombohedral r-HfO2-x structure. The DFT analysis shows that r-HfO2-x is not merely epitaxy-induced but may exist as a relaxed compound. Furthermore, the electronic structure of r-HfO2-x as determined by X-ray photoelectron spectroscopy and UV/Vis spectroscopy corresponds very well with the DFT-based prediction of a conducting defect band. The existence of a substoichiometric (semi-)conducting phase of HfO2-x is obviously an important ingredient to understand the mechanism of resistive switching in hafnium-oxide-based OxRAM.

YB1/p32, a nuclear Y-box binding protein 1, is a novel regulator of myoblast differentiation that interacts with Msx1 homeoprotein.

Precisely controlled cellular differentiation is essential for the proper development of vertebrate embryo and deregulated differentiation is a major cause of many human congenital diseases as well as cancer. Msx1 is a member of the homeoprotein family implicated in these processes, which inhibits the differentiation of skeletal muscle and other cell types, presumably by regulating transcription of target genes through interaction with other cellular factors. We presently show that YB1/p32, a nuclear Y-box binding protein 1, interacts with Msx1 homeoprotein and functions as a regulator of C2C12 myoblast differentiation. We demonstrate that YB1/p32 functionally interacts with Msx1 through its N-terminal region and colocalizes with Msx1 at the nuclear periphery. Moreover, we find that YB1/p32 is competent for inhibition of C2C12 myoblast differentiation, which is correlated with its activity as a negative regulator of MyoD gene expression and binding to the MyoD core enhancer region (CER). Furthermore, YB1/p32 cooperates with Msx1 in transcriptional repression and knocking down the expression of endogenous YB1 attenuates the effects of Msx1. Taken together, our study has uncovered a new function of YB1/p32, a regulator of skeletal muscle differentiation.

Potentially unstable intertrochanteric fractures.

OBJECTIVES: Evaluation of risk factors for loss of reduction in initially stable intertrochanteric fractures. DESIGN: Retrospective database analysis. SETTING: University teaching hospital. PATIENTS/PARTICIPANTS: Sixty-six patients over the age of 55 years presenting with fractures of the trochanteric region caused by a low-energy injury, classified as AO/OTA type 31-A1 (stable fracture in Evans classification). INTERVENTION: Treatment with a sliding compression hip screw. MAIN OUTCOME MEASUREMENT: The outcome examined in this study was loss of reduction as measured by the amount of medialization of the femoral shaft. RESULTS: Increased age (P = 0.01) and comminution of the lateral cortex (P = 0.0001) were factors significantly associated with excessive displacement. These 2 factors had a high degree of correlation (r = 0.76). CONCLUSIONS: A surgeon must be aware of iatrogenic fragmentation of the lateral cortex at the time of surgery in apparently stable intertrochanteric fractures in older patients because of the potential for subsequent loss of reduction.

Setdb1 is required for myogenic differentiation of C2C12 myoblast cells via maintenance of MyoD expression.

Setdb1, an H3-K9 specific histone methyltransferase, is associated with transcriptional silencing of euchromatic genes through chromatin modification. Functions of Setdb1 during development have been extensively studied in embryonic and mesenchymal stem cells as well as neurogenic progenitor cells. But the role of Sedtdb1 in myogenic differentiation remains unknown. In this study, we report that Setdb1 is required for myogenic potential of C2C12 myoblast cells through maintaining the expressions of MyoD and muscle-specific genes. We find that reduced Setdb1 expression in C2C12 myoblast cells severely delayed differentiation of C2C12 myoblast cells, whereas exogenous Setdb1 expression had little effect on. Gene expression profiling analysis using oligonucleotide micro-array and RNA-Seq technologies demonstrated that depletion of Setdb1 results in downregulation of MyoD as well as the components of muscle fiber in proliferating C2C12 cells. In addition, exogenous expression of MyoD reversed transcriptional repression of MyoD promoter-driven lucif-erase reporter by Setdb1 shRNA and rescued myogenic differentiation of C2C12 myoblast cells depleted of endogenous Setdb1. Taken together, these results provide new insights into how levels of key myogenic regulators are maintained prior to induction of differentiation.

Chemoprevention of Helicobacter pylori-associated gastric carcinogenesis in a mouse model: is it possible?

Although debates still exist whether Helicobacter pylori infection is really class I carcinogen or not, H. pylori has been known to provoke precancerous lesions like gastric adenoma and chronic atrophic gastritis with intestinal metaplasia as well as gastric cancer. Chronic persistent, uncontrolled gastric inflammations are possible basis for ensuing gastric carcinogenesis and H. pylori infection increased COX-2 expressions, which might be the one of the mechanisms leading to gastric cancer. To know the implication of long-term treatment of antiinflammatory drugs, rebamipide or nimesulide, on H. pylori-associated gastric carcinogenesis, we infected C57BL/6 mice with H. pylori, especially after MNU administration to promote carcinogenesis and the effects of the long-term administration of rebamipide or nimesulide were evaluated. C57BL/6 mice were sacrificed 50 weeks after H. pylori infection. Colonization rates of H. pylori, degree of gastric inflammation and other pathological changes including atrophic gastritis and metaplasia, serum levels and mRNA transcripts of various mouse cytokines and chemokines, and NF-kappaB binding activities, and finally the presence of gastric adenocarcinoma were compared between H. pylori infected group (HP), and H. pylori infected group administered with long-term rebamipide containing pellet diets (HPR) or nimesulide mixed pellets (HPN). Gastric mucosal expressions of ICAM-1, HCAM, MMP, and transcriptional regulations of NF-kappaB binding were all significantly decreased in HPR group than in HP group. Multi-probe RNase protection assay showed the significantly decreased mRNA levels of apoptosis related genes and various cytokines genes like IFN-gamma, RANTES, TNF-alpha, TNFR p75, IL-1beta in HPR group. In the experiment designed to provoke gastric cancer through MNU treatment with H. pylori infection, the incidence of gastric carcinoma was not changed between HP and HPR group, but significantly decreased in HPN group, suggesting the chemoprevention of H. pylori-associated gastric carcinogenesis by COX-2 inhibition. Long-term administration of antiinflammatory drugs should be considered in the treatment of H. pylori since they showed the molecular and biologic advantages with possible chemopreventive effect against H. pylori-associated gastric carcinogenesis. If the final concrete proof showing the causal relationship between H. pylori infection and gastric carcinogenesis could be obtained, that will shed new light on chemoprevention of gastric cancer, that is, that gastric cancer could be prevented through either the eradication of H. pylori or lessening the inflammation provoked by H. pylori infection in high risk group.

A novel patellofemoral scoring system for patellofemoral joint status.

BACKGROUND: We were not aware of a well-validated patellofemoral joint-specific scoring system. We performed this study to develop and validate a scoring system (Samsung Medical Center [SMC] patellofemoral scoring system) suitable for the evaluation of patellofemoral joint status. METHODS: We recruited 179 individuals consisting of a study group of 123 patients with anterior knee pain but without pain in another part of the knee, twenty-eight patients with knee pain other than anterior knee pain (group A), and twenty-eight healthy volunteers without knee pain (group B). Items in the development of the scoring system that showed a significant difference between the study group and group A and between the study group and the group B were selected. Test-retest reliability was measured by intraclass correlation coefficient, internal consistency was measured by the Cronbach alpha, content validity was assessed by ceiling and floor effects, and construct validity was determined by the association of the Feller scores and the SMC patellofemoral scores. RESULTS: After the item verification process, seventeen items (eight items for patellofemoral pain and nine items for patellofemoral function) were selected. Test-retest reliability for overall SMC patellofemoral scores showed excellent reliability (intraclass correlation coefficient, 0.85), and internal consistency was excellent (Cronbach alpha, 0.97). Floor and ceiling effects were acceptable (<30%) for all the items of the SMC patellofemoral scoring system, except one: sitting down on a chair, in the patellofemoral function score. The SMC patellofemoral scores showed moderate correlation with the Feller scores (ρ = -0.45). CONCLUSIONS AND CLINICAL RELEVANCE: The SMC patellofemoral score is a novel scoring system that distinguishes patients with anterior knee pain or patellofemoral dysfunction from patients with knee pain or dysfunction arising from other knee problems, and from those without knee pain. The reliability and validity of the SMC patellofemoral scoring system were verified in the present study.

PIAS1 negatively regulates ubiquitination of Msx1 homeoprotein independent of its SUMO ligase activity.

Posttranslational modifications play key roles in many cellular processes including proliferation and differentiation by modulating the activities of target proteins. PIAS1, a member of PIAS family of protein, mediates the modification of protein by SUMO and thereby regulates the function of its interacting protein partners. Here we report that PIAS1 negatively regulates ubiquitination of Msx1 homeoprotein, a regulator of myogenic differentiation, in a SUMO-independent manner. We demonstrate that ubiquitination and SUMOylation of Msx1 are not mutually exclusive but require the same C-terminal PIAS1 interaction domain. In addition, deletion of C-terminal domain increases the steady-state protein level of Msx1, while mutations of SUMO acceptor sites have no significant effect on the stability of Msx1 proteins. Moreover, we find that forced expression of PIAS1 inhibits ubiquitination and thereby increases the stability of Msx1 protein regardless of its activity as a SUMO ligase. Furthermore, repressor activity of Msx1 in transcription is strengthened in the presence of PIAS1. Taken together, our studies uncover a new function of PIAS1, which is to control the stability of its interacting protein partner in a SUMO independent manner.

Fractures to the posterior wall of the acetabulum managed with screws alone.

BACKGROUND: The use of a buttress plate in addition to lag screws has been recommended for fractures to the posterior wall of the acetabulum. However, there is a lack of possible criteria for the use of screws alone. This study aimed to evaluate the use of screws alone for fixation of posterior wall fractures to the acetabulum. METHODS: This study retrospectively examined 15 patients with a single fragmented or moderately comminuted posterior wall fracture of the acetabulum who had been treated with internal fixation using screws alone. The modified D'Aubigne and Postel's score system was used for the functional evaluation. RESULTS: The clinical results were excellent for nine hips, very good for one hip, good for four hips, and poor for one hip after follow-up period of more than 2 years. CONCLUSION: The use of screws alone can produce acceptable results for selected posterior wall fractures of the acetabulum.