Active site phosphoryl groups in the biphosphorylated phosphotransferase complex reveal dynamics in a millisecond time scale

AbstractThe N-terminal domain of Enzyme I (EIN) and phosphocarrier HPr can form a biphosphorylated complex when they are both phosphorylated by excess cellular phosphoenolpyruvate. Here we show that the electrostatic repulsion between the phosphoryl groups in the biphosphorylated complex results in characteristic dynamics at the active site in a millisecond time scale. The dynamics is localized to phospho-His15 and the stabilizing backbone amide groups of HPr, and does not impact on the phospho-His189 of EIN. The dynamics occurs with the kex of ∼500s−1 which compares to the phosphoryl transfer rate of ∼850s−1 between EIN and HPr. The conformational dynamics in HPr may be important for its phosphotransfer reactions with multiple partner proteins.Structured summary of protein interactionsEIN and HPr bind by nuclear magnetic resonance (View Interaction)

Spinal Nerve Root Swelling Mimicking Intervertebral Disc Herniation in Magnetic Resonance Imaging -A Case Report-

A herniated intervertebral disc is the most common type of soft tissue mass lesion within the lumbar spinal canal. Magnetic resonance imaging (MRI) is a useful tool for the assessment of patients with lower back pain and radiating pain, especially intervertebral disc herniation. MRI findings of intervertebral disc herniation are typical. However, from time to time, despite an apparently classic history and typical MRI findings suggestive of disc herniation, surgical exploration fails to reveal any lesion of an intervertebral disc. Our patient underwent lumbar disc surgery with the preoperative diagnosis of lumbar disc herniation; however, nothing could be found during the surgical procedure, except a swollen nerve root

Characterization of Porcine Endogenous Retrovirus Clones from the NIH Miniature Pig BAC Library

Pigs have been considered as donors for xenotransplantation in the replacement of human organs and tissues. However, porcine endogenous retroviruses (PERVs) might transmit new infectious disease to humans during xenotransplantation. To investigate PERV integration sites, 45 PERV-positive BAC clones, including 12 PERV-A, 16 PERV-B, and 17 PERV-C clones, were identified from the NIH miniature pig BAC library. The analysis of 12 selected full-length sequences of PERVs, including the long terminal repeat (LTR) region, identified the expected of open reading frame length, an indicative of active PERV, in all five PERV-C clones and one of the four PERV-B clones. Premature stop codons were observed in only three PERV-A clones. Also, eleven PERV integration sites were mapped using a 5000-rad IMpRH panel. The map locations of PERV-C clones have not been reported before, thus they are novel PERV clones identified in this study. The results could provide basic information for the elimination of site-specific PERVs in selection of pigs for xenotransplantation

Arrhythmia surgery for atrial fibrillation associated with atrial septal defect: Right-sided maze versus biatrial maze

BackgroundAlthough it has been inferred that a biatrial maze procedure for atrial fibrillation in left-sided heart lesions may lead to better outcomes compared with a limited left atrial lesion set, it remains controversial whether the biatrial maze procedure is superior to the right atrial maze procedure in right-sided heart lesions.MethodsA retrospective review was performed for 56 adults who underwent surgical closure of atrial septal defect and various maze procedures for atrial fibrillation between June 1998 and February 2011. The median age at operation was 59 years (range, 34-79 years). Clinical manifestations of atrial fibrillation were paroxysmal in 8 patients, persistent in 15 patients, and long-standing persistent in 33 patients. A right atrial maze procedure was performed in 23 patients (group 1), and a biatrial maze procedure was performed in 33 patients (group 2). Treatment failure was defined as atrial fibrillation recurrence, development of atrial flutter or other types of atrial tachyarrhythmia, or implantation of a permanent pacemaker. The Cox proportional hazards model was used to identify risk factors for decreased time to treatment failure.ResultsDuring the median follow-up period of 49 months (range, 5-149 months), there was no early death and 1 late noncardiac death. On Cox survival model, group 1 showed a significantly decreased time to treatment failure in comparison with group 2 (hazard ratio, 5.11; 95% confidence interval, 1.59-16.44; P = .006). Maintenance of normal sinus rhythm without any episode of atrial fibrillation recurrence at 2 and 5 years postoperatively was 57% and 45% in group 1, respectively, and 82% and 69% in group 2, respectively.ConclusionsLeft-sided ablation in addition to a right atrial maze procedure leads to better electrophysiologic outcome in atrial fibrillation associated with atrial septal defect

Soft, wireless periocular wearable electronics for real-time detection of eye vergence in a virtual reality toward mobile eye therapies

Ocular disorders are currently affecting the developed world, causing loss of productivity in adults and children. While the cause of such disorders is not clear, neurological issues are often considered as the biggest possibility. Treatment of strabismus and vergence requires an invasive surgery or clinic-based vision therapy that has been used for decades due to the lack of alternatives such as portable therapeutic tools. Recent advancement in electronic packaging and image processing techniques have opened the possibility for optics-based portable eye tracking approaches, but several technical and safety hurdles limit the implementation of the technology in wearable applications. Here, we introduce a fully wearable, wireless soft electronic system that offers a portable, highly sensitive tracking of eye movements (vergence) via the combination of skin-conformal sensors and a virtual reality system. Advancement of material processing and printing technologies based on aerosol jet printing enables reliable manufacturing of skin-like sensors, while a flexible electronic circuit is prepared by the integration of chip components onto a soft elastomeric membrane. Analytical and computational study of a data classification algorithm provides a highly accurate tool for real-time detection and classification of ocular motions. In vivo demonstration with 14 human subjects captures the potential of the wearable electronics as a portable therapy system, which can be easily synchronized with a virtual reality headset

Premixed Calcium Silicate-Based Root Canal Sealer Reinforced with Bioactive Glass Nanoparticles to Improve Biological Properties

Recently, bioactive glass nanoparticles (BGns) have been acknowledged for their ability to promote interactions with the periapical tissue and enhance tissue regeneration by releasing therapeutic ions. However, there have been no studies on calcium silicate sealers with bioactive glass nanoparticle (BGn) additives. In the present study, a premixed calcium silicate root canal sealer reinforced with BGn (pre-mixed-RCS@BGn) was developed and its physicochemical features and biological effects were analyzed. Three specimens were in the trial: 0%, 0.5%, and 1% bioactive glass nanoparticles (BGns) were gradually added to the premixed type of calcium silicate-based sealer (pre-mixed-RCS). To elucidate the surface properties, scanning electron microscopy, X-ray diffraction, and energy-dispersive spectroscopy were used and flowability, setting time, solubility, and radiopacity were analyzed to evaluate the physical properties. Chemical properties were investigated by water contact angle, pH change, and ion release measurements. The antibacterial effects of the bioactive set sealers were tested with Enterococcus faecalis and the viability of human bone marrow-derived mesenchymal stem cells (hMSCs) with this biomaterial was examined. In addition, osteogenic differentiation was highly stimulated, which was confirmed by ALP (Alkaline phosphatase) activity and the ARS (Alizarin red S) staining of hMSCs. The pre-mixed-RCS@BGn satisfied the ISO standards for root canal sealers and maintained antimicrobial activity. Moreover, pre-mixed-RCS@BGn with more BGns turned out to have less cytotoxicity than pre-mixed-RCS without BGns while promoting osteogenic differentiation, mainly due to calcium and silicon ion release. Our results suggest that BGns enhance the biological properties of this calcium silicate-based sealer and that the newly introduced pre-mixed-RCS@BGn has the capability to be applied in dental procedures as a root canal sealer. Further studies focusing more on the biocompatibility of pre-mixed-RCS@BGn should be performed to investigate in vivo systems, including pulp tissue

A Dual Inhibitor of the Proteasome Catalytic Subunits LMP2 and Y Attenuates Disease Progression in Mouse Models of Alzheimer\u27s Disease

The immunoproteasome (iP) is a variant of the constitutive proteasome (cP) that is abundantly expressed in immune cells which can also be induced in somatic cells by cytokines such as TNF-α or IFN-γ. Accumulating evidence support that the iP is closely linked to multiple facets of inflammatory response, eventually leading to the development of several iP inhibitors as potential therapeutic agents for autoimmune diseases. Recent studies also found that the iP is upregulated in reactive glial cells surrounding amyloid β (Aβ) deposits in brains of Alzheimer\u27s disease (AD) patients, but the role it plays in the pathogenesis of AD remains unclear. In this study, we investigated the effects of several proteasome inhibitors on cognitive function in AD mouse models and found that YU102, a dual inhibitor of the iP catalytic subunit LMP2 and the cP catalytic subunit Y, ameliorates cognitive impairments in AD mouse models without affecting Aβ deposition. The data obtained from our investigation revealed that YU102 suppresses the secretion of inflammatory cytokines from microglial cells. Overall, this study indicates that there may exist a potential link between LMP2/Y and microglia-mediated neuroinflammation and that inhibition of these subunits may offer a new therapeutic strategy for AD