Tonicity response element binding protein associated with neuronal cell death in the experimental diabetic retinopathy

AIM: To study the contribution of tonicity response element binding protein (TonEBP) in retinal ganglion cell (RGC) death of diabetic retinopathy (DR). METHODS: Diabetes was induced in C57BL/6 mice by five consecutive intraperitoneal injections of 55 mg/kg streptozotocin (STZ). Control mice received vehicle (phosphate -buffered saline). All mice were killed 2mo after injections, and the extent of cell death and the protein expression levels of TonEBP and aldose reductase (AR) were examined. RESULTS: The TonEBP and AR protein levels and the death of RGC were significantly increased in the retinas of diabetic mice compared with controls 2mo after the induction of diabetes. Terminal deoxynucleotidyl transferase (TdT) -mediated dUTP nick end labeling (TUNEL) -positive signals co -localized with TonEBP immunoreactive RGC. These changes were increased in the diabetic retinas compared with controls. CONCLUSION: The present data show that AR and TonEBP are upregulated in the DR and TonEBP may contribute to apoptosis of RGC in the DR.close2

Role of Matrix Metalloproteinase 3-mediated alpha-Synuclein Cleavage in Dopaminergic Cell Death

Evidence suggests that the C-terminal truncation of alpha-synuclein is equally important as aggregation of alpha-synuclein in Parkinson disease (PD). Our previous results showed that an endopeptidase, matrix metalloproteinase-3 (MMP3), was induced and activated in dopaminergic (DA) cells upon stress conditions. Here, we report that MMP3 cleaved alpha-synuclein in vitro and in vivo and that alpha-synuclein and MMP3 were co-localized in Lewy bodies (LB) in the postmortem brains of PD patients. Incubation of alpha-synuclein with the catalytic domain of MMP3 (cMMP3) resulted in generation of several peptides, and the peptide profiles of WT alpha-synuclein (WTsyn) and A53T mutant (A53Tsyn) were different. Combined analysis using mass spectrometry and N-terminal determination revealed that MMP3 generated C-terminally truncated peptides of amino acids 1-78, 1-91, and 1-93 and that A53Tsyn produced significantly higher quantities of these peptides. Similar sizes of peptides were detected in N27 DA cells under oxidative stress and RNA interference to knock down MMP3-attenuated peptide generation. Co-overexpression of cMMP3 with either WTsyn or A53Tsyn led to a reduction in Triton X-100-insoluble aggregates and an increase in protofibril-like small aggregates. In addition, overexpression of the 1-93-amino acid peptide in the substantia nigra led to DA neuronal loss without LB-like aggregate formation. The results strongly indicate that MMP3 digestion of alpha-synuclein in DA neurons plays a pivotal role in the progression of PD through modulation of alpha-synuclein in aggregation, LB formation, and neurotoxicity

Study of the effect of nano-sized precipitates on the mechanical properties of boron-added low-carbon steels by neutron scattering techniques

The effect of nano-sized precipitates on the mechanical properties of boron-added low-carbon steels was studied by neutron scattering techniques such as powder diffraction, small-angle scattering and particle tracking autography

Spin configuration of top quark pair production with large extra dimensions at photon-photon colliders

Top quark pair production at photon-photon colliders is studied in low scale quantum gravity scenario. From the dependence of the cross sections on the spin configuration of the top quark and anti-quark, we introduce a new observable, top spin asymmetry. It is shown that there exists a special top spin basis where with the polarized parent electron beams the top spin asymmetry vanishes in the standard model but retains substantial values with the large extra dimension effects. We also present lower bounds of the quantum gravity scale $M_S$ from total cross sections with various combinations of the laser, electron beam, and top quark pair polarizations. The measurements of the top spin state $(t_\uparrow\bar{t}_\downarrow)$ with unpolarized initial beams are shown to be most effective, enhancing by about 5% the $M_S$ bounds with respect to totally unpolarized case.Comment: 18 pages, 4 figures, ReVTe

Long-term effect of stereotactic body radiation therapy for primary hepatocellular carcinoma ineligible for local ablation therapy or surgical resection. Stereotactic radiotherapy for liver cancer

<p>Abstract</p> <p>Background</p> <p>We evaluated the long-term effect of stereotactic body radiation therapy (SBRT) for primary small hepatocellular carcinoma (HCC) ineligible for local therapy or surgery.</p> <p>Methods</p> <p>Forty-two HCC patients with tumors ≤ 100 cc and ineligible for local ablation therapy or surgical resection were treated with SBRT: 30-39 Gy with a prescription isodose range of 70-85% (median 80%) was delivered daily in three fractions. Median tumor volume was 15.4 cc (3.0-81.8) and median follow-up duration 28.7 months (8.4-49.1).</p> <p>Results</p> <p>Complete response (CR) for the in-field lesion was initially achieved in 59.6% and partial response (PR) in 26.2% of patients. Hepatic out-of-field progression occurred in 18 patients (42.9%) and distant metastasis developed in 12 (28.6%) patients. Overall in-field CR and overall CR were achieved in 59.6% and 33.3%, respectively. Overall 1-year and 3-year survival rates were 92.9% and 58.6%, respectively. In-field progression-free survival at 1 and 3 years was 72.0% and 67.5%, respectively. Patients with smaller tumor had better in-field progression-free survival and overall survival rates (<32 cc vs. ≥32 cc, <it>P </it>< 0.05). No major toxicity was encountered but one patient died with extrahepatic metastasis and radiation-induced hepatic failure.</p> <p>Conclusions</p> <p>SBRT is a promising noninvasive-treatment for small HCC that is ineligible for local treatment or surgical resection.</p