Ionizing radiation induces blockade of c-Jun N-terminal kinase-dependent cell death pathway in a manner correlated with p21(Cip/WAF1) induction in primary cultured normal human fibroblasts

During radiotherapy of cancer, neighboring normal cells may receive sub-lethal doses of radiation. To investigate whether such low levels of radiation modulate normal cell responses to death stimuli, primary cultured human fibroblasts were exposed to various doses of gamma-rays. Analysis of cell viability using an exclusion dye propidium iodide revealed that the irradiation up to 10 Gy killed the fibroblasts only to a minimal extent. In contrast, the cells efficiently lost their viability when exposed to 0.5-0.65 mM H(2)O(2). This type of cell death was accompanied by JNK activation, and was reversed by the use of a JNK-specific inhibitor SP600125. Interestingly, H(2)O(2) failed to kill the fibroblasts when these cells were pre-irradiated, 24 h before H(2)O(2) treatment, with 0.25-0.5 Gy of gamma-rays. These cytoprotective doses of gamma-rays did not enhance cellular capacity to degrade H(2)O(2), but elevated cellular levels of p21(Cip/WAF1), a p53 target that can suppress H(2)O(2)-induced cell death by blocking JNK activation. Consistently, H(2)O(2)-induced JNK activation was dramatically suppressed in the pre-irradiated cells. The overall data suggests that ionizing radiation can impart normal fibroblasts with a survival advantage against oxidative stress by blocking the process leading to JNK activation.     

Delta-secretase cleavage of Tau mediates its pathology and propagation in Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with age as a major risk factor. AD is the most common dementia with abnormal structures, including extracellular senile plaques and intraneuronal neurofibrillary tangles, as key neuropathologic hallmarks. The early feature of AD pathology is degeneration of the locus coeruleus (LC), which is the main source of norepinephrine (NE) supplying various cortical and subcortical areas that are affected in AD. The spread of Tau deposits is first initiated in the LC and is transported in a stepwise manner from the entorhinal cortex to the hippocampus and then to associative regions of the neocortex as the disease progresses. Most recently, we reported that the NE metabolite DOPEGAL activates delta-secretase (AEP, asparagine endopeptidase) and triggers pathological Tau aggregation in the LC, providing molecular insight into why LC neurons are selectively vulnerable to developing early Tau pathology and degenerating later in the disease and how δ-secretase mediates the spread of Tau pathology to the rest of the brain. This review summarizes our current understanding of the crucial role of δ-secretase in driving and spreading AD pathologies by cleaving multiple critical players, including APP and Tau, supporting that blockade of δ-secretase may provide an innovative disease-modifying therapeutic strategy for treating AD.Subject terms: Neurodegeneration, Alzheimer''s disease     

Reversible replication between ordered mesoporous silica and mesoporous carbon

Highly ordered mesoporous silica can be regenerated from a mesoporous carbon CMK-3 that is a negative replica of mesoporous silica SBA-15, indicating reversible replication between carbon and inorganic materials.     

Stimulated Raman scattering measurements of H2 vibration–vibration transfer

We present a new set of V–V rate coefficients for vibrational levels 0–5 in H₂ at 300 K, measured using a stimulated Raman–spontaneous Raman pump/probe apparatus. The measured rate of the non-resonant process, H₂(v = 1) + H₂(v = 1) → H₂(v = 0) + H₂(v = 2), is consistent with the previously reported experimental value of Kreutz et al. However, semi-classical predictions of such non-resonant processes, using the identical inter-molecular potential and methodology to that given by Cacciatore and Billing, results in rates which are too slow, by a factor of approximately 3. For the “resonant” V–V process, H₂(v = 1) + H₂(v = 0) → H₂(v = 0) + H₂(v = 1), the semi-classical rate is found to be too slow by an even larger factor, of approximately 30, compared to the experimental rate, but consistent with the previously reported experimental result of Farrow and Chandler. Further, unlike the semi-classical model prediction in which the (1, 1 → 2, 0) process rate is predicted to exceed that of the (1, 0 → 0, 1) process, the experimental data shows it to be a factor of approximately 2.5 less, suggesting that semi-classical methods that treat the rotational motion classically are unsuitable for the highly anharmonic H₂ molecule. The ratio of pure rotation and rotation–vibration Raman cross sections for scattering from levels 0 and 1 is also determined, with results which agree with calculations of Schwartz and LeRoy, but are somewhat larger than previous experimental results of Cureton.     

New tetradentate Schiff-base polymers: preparation of poly[2,5-(didodecyloxy)phenylene-1,4-diyl-alt-N,N-(o-phenylene)-bis(salicylideneiminato-4,4-diyl)] and poly[2,5-(didodecyloxy)phenylene-1,4-diyl-alt-N,N-(alkylidene)-bis(salicylideneiminato-4,4-diyl)]s

New tetradentate Schiff-base polymers, in which phenylene units alternate with salicylideneiminato units, have been prepared by condensation of 2,5-(didodecyloxy)-1,4-bis(3-formyl-4-hydroxyphenyl)benzene (DFHB) with appropriate diamines in a mixed solution of CHCl₃/toluene/acetic acid with 31-79% yields. DFHB as the key building block was prepared by the Suzuki reaction of 2,5-(didodecyloxy)benzene-1,4-diboronic acid with 5-bromosalicylaldehyde in a two-phase solution of tetrahydrofuran/water in the presence of NaHCO₃/Pd(PPh₃)₄ in 45% yield. The molecular structures of the prepared compounds were identified by spectroscopy. Their absorption spectroscopic profiles have been analyzed.     

RELATIVE REACTIVITIES OF THE EXCITED STATES OF FUROCOUMARINS FOR [2+2] PHOTOCYCLOADDITION REACTION WITH TETRAMETHYLETHYLENE

Abstract— The Stern-Volmer constants for fluorescence quenching by tetramethylethylene decrease in the order DMC ≫ DHP > F-2 > 8-MOP. The same order was observed for the quantum yields of [2+2] cycloaddition reaction with tetramethylethylene on direct irradiation. In [2+2] photocycloaddition of F-2 with tetramethylethylene in ethanol, the ratio of quantum yields deduced from singlet and triplet states of F-2; φ₃⁰/φ₁⁰, is about 5. The excited triplet state is the reactive state for the [2+2] photocycloaddition of F-2 with tetramethylethylene in solution but the excited singlet state of F-2 becomes very important in biological conditions.     

Ruthenium‐catalyzed formal alkyl group transfer: Synthesis of quinolines from nitroarenes and alkylammonium halides

Nitroarenes are reductively cyclized with an array of tetraalkylammonium halides and trialkylarnmonium chlorides in the presence of a catalytic amount of a ruthenium catalyst along with tin(II) chloride dihydrate at 180° to afford the corresponding quinolines in moderate to good yields. The addition of tin(II) chloride dihydrate is necessary for the effective formation of quinolines and toluene is the solvent of choice. A reaction pathway involving initial reduction of nitroarenes to anilines and conversion of alkylammonium halides to alkylamines, alkyl group transfer from alkylamines to anilines to form an imine, dimerization of imine, and heteroannulation is proposed for this catalytic process.     

Temperature-dependent intermolecular force measurement of poly(N-isopropylacrylamide) grafted surface with protein

We have investigated the temperature dependence of the intermolecular force between poly(N-isopropylacrylamide) (PNiPAM) grafted surface and bovine serum albumin (BSA) in phosphate buffer (pH 7.4) using atomic force microscopy at the nanonewton scale. These observations show that the interaction force is nearly zero below the phase transition temperature of PNiPAM and that it increases steeply during the phase transition. Since the PNiPAM chains are grafted onto the aminosilane (gamma-aminopropyltriethoxysilane)-treated silicon wafer, we measured the force-distance curve of BSA-immobilized tips for the bare and the aminosilane-treated silicon wafer. These surfaces show no temperature dependence and their values are different from those of the PNiPAM-grafted surfaces at 30 degrees C. The results indicate that the measured adhesion force is between the PNiPAM-grafted surface and the BSA-immobilized tip. Our studies on the intermolecular force between other surfaces (CH(3)- and COOH-terminated self-assembled monolayers) and the BSA-immobilized tip indicate that the variation in the intermolecular force between the PNiPAM surface and BSA with temperature can be attributed to the changes in the properties of the PNiPAM chains. From consideration of the PNiPAM phase transition mechanism, it is speculated that the intermolecular force between the PNiPAM-grafted surface and BSA would be affected by changes in the arrangement of the bound water molecules around the PNiPAM chain and by changes in the conformation (i.e., in the chain mobility) of the PNiPAM chain during the phase transition.