Burkhardt-Cottingham sum rule and forward spin polarizabilities in Heavy Baryon Chiral Perturbation Theory

We study spin-dependent sum rules for forward virtual Compton scattering(VVCS) off the nucleon in heavy baryon chiral perturbation theory at order $O(p^4)$. We show how these sum rules can be evaluated from low energy expansions (in the virtual photon energy) of the forward VVCS amplitudes. We study in particular the Burkhardt -Cottingham sum rule in HBChPT and higher terms in the low energy expansion, which can be related to the generalized forward spin polarizabilities of the nucleon. The dependence of these observables on the photon virtuality $Q^2$ can be accessed, at small and intermediate $Q^2$ values, from existing and forthcoming data at Jefferson Lab.Comment: 16 pages,4 fig

Reversine suppresses oral squamous cell carcinoma via cell cycle arrest and concomitantly apoptosis and autophagy

<p>Abstract</p> <p>Background</p> <p>The effective therapies for oral cancer patients of stage III and IV are generally surgical excision and radiation combined with adjuvant chemotherapy using 5-Fu and Cisplatin. However, the five-year survival rate is still less than 30% in Taiwan. Therefore, evaluation of effective drugs for oral cancer treatment is an important issue. Many studies indicated that aurora kinases (A, B and C) were potential targets for cancer therapies. Reversine was proved to be a novel aurora kinases inhibitor with lower toxicity recently. In this study, the potentiality for reversine as an anticancer agent in oral squamous cell carcinoma (OSCC) was evaluated.</p> <p>Methods</p> <p>Effects of reversine on cell growth, cell cycle progress, apoptosis, and autophagy were evaluated mainly by cell counting, flow cytometry, immunoblot, and immunofluorescence.</p> <p>Results</p> <p>The results demonstrated that reversine significantly suppressed the proliferation of two OSCC cell lines (OC2 and OCSL) and markedly rendered cell cycle arrest at G2/M stage. Reversine also induced cell death via both caspase-dependent and -independent apoptosis. In addition, reversine could inhibit Akt/mTORC1 signaling pathway, accounting for its ability to induce autophagy.</p> <p>Conclusions</p> <p>Taken together, reversine suppresses growth of OSCC via multiple mechanisms, which may be a unique advantage for developing novel therapeutic regimens for treatment of oral cancer in the future.</p

Training Effects of Virtual Reality on Reaching Behaviors in Children with Cerebral Palsy: Case Report

Virtual reality (VR) is a computer technology that artificially generates sensory information in a form that people perceive as real-world objects and events. It has been proposed that VR can improve upper-extremity function in children with cerebral palsy (CP) by decreasing physical disabilities, precisely adjusting the difficulty of task and feedback, enhancing motivation and manipulating perceptual information. The purpose of this study was to investigate the training effects of VR on reaching behavior in a child with CP. This case was a 6-year-old boy with spastic quadriplegic CP who had good cooperation and normal cognition. A single-subject A-B-A design was used. The case received 3 baseline, 4 intervention, and 2 follow-up measures. He received a 4-week (3 times a week) individualized VR training using VR-hand function training system and Eyetoy-play system with therapist\u27s manual guidance. The outcome measures included (1) four reaching kinematic parameters (movement time (MT), path, peak velocity (PV), and number of movement units (MU)) in 2 activities (pegboard and mail-delivery) at 3 directions (abduction, adduction, and forward); (2) touching a swing ball; and (3) the fine motor domain of Peabody Development Motor Scale-2nd edition (PDMS2). Visual inspection and 2-standard deviation band method were used to compare the outcome measures between the two adjacent phases. Improvements were found in the kinematic parameters in all directions from baseline to intervention, and the effects were maintained in some directions from intervention to follow-up. Improvement was also shown in the ability to touch a swing ball, but the effect was not maintained from intervention to follow-up. Furthermore, there was an increase (11 points) in the PDMS2 scores from baseline to intervention and an increase (1 point) from intervention to follow-up. This case study demonstrated the potential effect of VR training program to improve the upper-extremity function in children with CP. The training effects might retain for 1 month post intervention

Preparation and Characterization of Pure Rutile TiO 2

Pure rutile-phase TiO2 (r-TiO2) was synthesized by a simple one pot experiment under hydrothermal condition using titanium (IV) n-butoxide as a Ti-precursor and HCl as a peptizer. The TiO2 products were characterized by XRD, TEM, ESCA, and BET surface area measurement. The r-TiO2 were rodlike in shape with average size of ∼61×32 nm at hydrothermal temperature of 220°C for 10 h. Hydrothermal treatment at longer reaction time increased the tendency of crystal growth and also decreased the BET surface area. The degradation of methylene blue was selected as a test reaction to confer the photocatalytic activity of as-obtained r-TiO2. The results showed a strong correlation between the structure evolution, particle size, and photocatalytic performance of r-TiO2. Furthermore, the r-TiO2-based solar cell was prepared for the photovoltaic characteristics study, and the best efficiency of ~3.16% was obtained

TNF-α Mediates Eosinophil Cationic Protein-induced Apoptosis in BEAS-2B Cells

<p>Abstract</p> <p>Background</p> <p>Eosinophilic granulocytes are important for the human immune system. Many cationic proteins with cytotoxic activities, such as eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN), are released from activated eosinophils. ECP, with low RNase activity, is widely used as a biomarker for asthma. ECP inhibits cell viability and induces apoptosis to cells. However, the specific pathway underlying the mechanisms of ECP-induced cytotoxicity remains unclear. This study investigated ECP-induced apoptosis in bronchial epithelial BEAS-2B cells and elucidated the specific pathway during apoptosis.</p> <p>Results</p> <p>To address the mechanisms involved in ECP-induced apoptosis in human BEAS-2B cells, investigation was carried out using chromatin condensation, cleavage of poly (ADP-ribose) polymerase (PARP), sub-G1 distribution in cell cycle, annexin V labeling, and general or specific caspase inhibitors. Caspase-8-dependent apoptosis was demonstrated by cleavage of caspase-8 after recombinant ECP treatment, accompanied with elevated level of tumor necrosis factor alpha (TNF-α). Moreover, ECP-induced apoptosis was effectively inhibited in the presence of neutralizing anti-TNF-α antibody.</p> <p>Conclusion</p> <p>In conclusion, our results have demonstrated that ECP increased TNF-α production in BEAS-2B cells and triggered apoptosis by caspase-8 activation through mitochondria-independent pathway.</p

An epigenetic blockade of cognitive functions in the neurodegenerating brain

Cognitive decline is a debilitating feature of most neurodegenerative diseases of the central nervous system, including Alzheimer’s disease [superscript 1]. The causes leading to such impairment are only poorly understood and effective treatments are slow to emerge [superscript 2]. Here we show that cognitive capacities in the neurodegenerating brain are constrained by an epigenetic blockade of gene transcription that is potentially reversible. This blockade is mediated by histone deacetylase 2, which is increased by Alzheimer’s-disease-related neurotoxic insults in vitro, in two mouse models of neurodegeneration and in patients with Alzheimer’s disease. Histone deacetylase 2 associates with and reduces the histone acetylation of genes important for learning and memory, which show a concomitant decrease in expression. Importantly, reversing the build-up of histone deacetylase 2 by short-hairpin-RNA-mediated knockdown unlocks the repression of these genes, reinstates structural and synaptic plasticity, and abolishes neurodegeneration-associated memory impairments. These findings advocate for the development of selective inhibitors of histone deacetylase 2 and suggest that cognitive capacities following neurodegeneration are not entirely lost, but merely impaired by this epigenetic blockade.Stanley Medical Research InstituteNational Institute of Neurological Disorders and Stroke (U.S.) (RO1NS078839)Swiss National Science FoundationBard Richmond (Fellowship)Simons FoundationTheodor und Ida Herzog-Egli Foundatio

Crebinostat: A novel cognitive enhancer that inhibits histone deacetylase activity and modulates chromatin-mediated neuroplasticity

Long-term memory formation is known to be critically dependent upon de novo gene expression in the brain. As a consequence, pharmacological enhancement of the transcriptional processes mediating long-term memory formation provides a potential therapeutic strategy for cognitive disorders involving aberrant neuroplasticity. Here we focus on the identification and characterization of small molecule inhibitors of histone deacetylases (HDACs) as enhancers of CREB (cAMP response element-binding protein)-regulated transcription and modulators of chromatin-mediated neuroplasticity. Using a CREB reporter gene cell line, we screened a library of small molecules structurally related to known HDAC inhibitors leading to the identification of a probe we termed crebinostat that produced robust activation of CREB-mediated transcription. Further characterization of crebinostat revealed its potent inhibition of the deacetylase activity of recombinant class I HDACs 1, 2, 3, and class IIb HDAC6, with weaker inhibition of the class I HDAC8 and no significant inhibition of the class IIa HDACs 4, 5, 7, and 9. In cultured mouse primary neurons, crebinostat potently induced acetylation of both histone H3 and histone H4 as well as enhanced the expression of the CREB target gene Egr1 (early growth response 1). Using a hippocampus-dependent, contextual fear conditioning paradigm, mice systemically administered crebinostat for a ten day time period exhibited enhanced memory. To gain insight into the molecular mechanisms of memory enhancement by HDAC inhibitors, whole genome transcriptome profiling of cultured mouse primary neurons treated with crebinostat, combined with bioinformatic analyses of CREB-target genes, was performed revealing a highly connected protein–protein interaction network reflecting modules of genes important to synaptic structure and plasticity. Consistent with these findings, crebinostat treatment increased the density of synapsin-1 punctae along dendrites in cultured neurons. Finally, crebinostat treatment of cultured mouse primary neurons was found to upregulate Bdnf (brain-derived neurotrophic factor) and Grn (granulin) and downregulate Mapt (tau) gene expression—genes implicated in aging-related cognitive decline and cognitive disorders. Taken together, these results demonstrate that crebinostat provides a novel probe to modulate chromatin-mediated neuroplasticity and further suggests that pharmacological optimization of selective of HDAC inhibitors may provide an effective therapeutic approach for human cognitive disorders.National Institutes of Health (U.S.) (R01DA028301)National Institutes of Health (U.S.) (R01NS051874)Stanley Medical Research InstituteHoward Hughes Medical Institut

A novel pathway regulates memory and plasticity via SIRT1 and miR-134

The NAD-dependent deacetylase Sir2 was initially identified as a mediator of replicative lifespan in budding yeast and was subsequently shown to modulate longevity in worms and flies. Its mammalian homologue, SIRT1, seems to have evolved complex systemic roles in cardiac function, DNA repair and genomic stability. Recent studies suggest a functional relevance of SIRT1 in normal brain physiology and neurological disorders. However, it is unknown if SIRT1 has a role in higher-order brain functions. We report that SIRT1 modulates synaptic plasticity and memory formation via a microRNA-mediated mechanism. Activation of SIRT1 enhances, whereas its loss-of-function impairs, synaptic plasticity. Surprisingly, these effects were mediated via post-transcriptional regulation of cAMP response binding protein (CREB) expression by a brain-specific microRNA, miR-134. SIRT1 normally functions to limit expression of miR-134 via a repressor complex containing the transcription factor YY1, and unchecked miR-134 expression following SIRT1 deficiency results in the downregulated expression of CREB and brain-derived neurotrophic factor (BDNF), thereby impairing synaptic plasticity. These findings demonstrate a new role for SIRT1 in cognition and a previously unknown microRNA-based mechanism by which SIRT1 regulates these processes. Furthermore, these results describe a separate branch of SIRT1 signalling, in which SIRT1 has a direct role in regulating normal brain function in a manner that is disparate from its cell survival functions, demonstrating its value as a potential therapeutic target for the treatment of central nervous system disorders

Atomistic nucleation sites of Pt nanoparticles on N-doped carbon nanotubes

[[abstract]]The atomistic nucleation sites of Pt nanoparticles (Pt NPs) on N-doped carbon nanotubes (N-CNTs) were investigated using C and N K-edge and Pt L3-edge X-ray absorption near-edge structure (XANES)/extended X-ray absorption fine structure (EXAFS) spectroscopy. Transmission electron microscopy and XANES/EXAFS results revealed that the self-organized Pt NPs on N-CNTs are uniformly distributed because of the relatively high binding energies of the adsorbed Pt atoms at the imperfect sites. During the atomistic nucleation process of Pt NPs on N-CNTs, stable Pt–C and Pt–N bonds are presumably formed, and charge transfer occurs at the surface/interface of the N-CNTs. The findings in this study were consistent with density functional theory calculations performed using cluster models for the undoped, substitutional-N-doped and pyridine-like-N-doped CNTs.[[journaltype]]國外[[incitationindex]]SCI[[booktype]]紙本[[countrycodes]]GB