Neuregulin-1 attenuates cognitive function impairments in a transgenic mouse model of Alzheimer's disease.

The neuregulin (NRG) family of epidermal growth factor-related proteins is composed of a wide variety of soluble and membrane-bound proteins that exert their effects via the tyrosine kinase receptors ErbB2-ErbB4. In the nervous system, the functions of NRG1 are essential for peripheral myelination, the establishment and maintenance of neuromuscular and sensorimotor systems and the plasticity of cortical neuronal circuits. In the present study, we report that an intracerebroventricular infusion of NRG1 attenuated cognitive impairments in 13-month-old Tg2576 mice, an animal model of Alzheimer's disease (AD). In addition, according to Golgi-Cox staining, NRG1 rescued the reduction in the number of dendritic spines detected in the brains of Tg2576 mice compared with vehicle (PBS)-infused mice. This result was also corroborated in vitro as NRG1 attenuated the oligomeric amyloid beta peptide(1-42) (Aß(1-42))-induced decrease in dendritic spine density in rat primary hippocampal neuron cultures. NRG1 also alleviated the decrease in neural differentiation induced by oligomeric Aß(1-42) in mouse fetal neural stem cells. Collectively, these results suggest that NRG1 has a therapeutic potential for AD by alleviating the reductions in dendritic spine density and neurogenesis found in AD brains.

Graphene mode-locked femtosecond Cr:ZnSe laser at 2500 nm.

We report, for the first time to our knowledge, femtosecond pulse generation from a graphene mode-locked Cr:ZnSe laser at 2500 nm. To minimize the insertion losses at the lasing wavelength, high-quality monolayer graphene transferred on a CaF(2) substrate was used in the experiments. Once mode-locking was initiated, the laser generated a stable train of 226 fs pulses with a time-bandwidth product of 0.39. The mode-locked laser operated at a pulse repetition rate of 77 MHz and produced 80 mW output power with an incident pump power of 1.6 W. To our knowledge, this is the longest laser wavelength at which graphene-based passive mode-locking has been demonstrated to date.

The negative hydrogen Penning ion gauge ion source for KIRAMS-13 cyclotron.

The cold-cathode-type Penning ion gauge (PIG) ion source for the internal ion source of KIRAMS-13 cyclotron has been used for generation of negative hydrogen ions. The dc H-beam current of 650 microA from the PIG ion source with the Dee voltage of 40 kV and arc current of 1.0 A is extrapolated from the measured dc extraction beam currents at the low extraction dc voltages. The output optimization of PIG ion source in the cyclotron has been carried out by using various chimneys with different sizes of the expansion gap between the plasma boundary and the chimney wall. This paper presents the results of the dc H-extraction measurement and the expansion gap experiment.

p-benzoquinone-benzene clusters as potential nanomechanical devices: a theoretical study.

The equilibrium structures and binding energies of the benzene complexes of p-benzoquinones (PBQ) and its negatively charged anionic species (PBQ- and PBQ2-) have been investigated theoretically using second-order Møller-Plesset calculations. While neutral p-benzoquinone-benzene clusters (PBQ-Bz) prefer to have a parallel displaced geometry (P-c), CH...pi interactions (T-shaped geometries) prevail in the di-anionic PBQ-benzene (PBQ2- -Bz) complexes (T-e2-). Studies on dianionic p-benzoquinone-benzene clusters showed that two nonbonded intermolecular interactions compete in the most stable conformation. One is H-bonding interaction (C-H...O type) between carbonyl oxygen of p-benzoquinone and one of the hydrogen atoms of benzene, and the other is a pi-H interaction between pi-electron cloud of PBQ2- and another hydrogen atom of benzene. Blueshifted H-bonds were observed in T-shaped clusters. The changes in the geometrical preference of PBQ-Bz complex upon addition of electrons would be useful in designing optimized molecular mechanical devices based on the edge-to-face and face-to-face aromatic interactions.

Maintenance of alpha-helical structures by phenyl rings in the active-site tyrosine triad contributes to catalysis and stability of ketosteroid isomerase from Pseudomonas putida biotype B.

Ketosteroid isomerase (KSI) from Pseudomonas putida biotype B is a homodimeric enzyme catalyzing an allylic rearrangement of Delta5-3-ketosteroids at rates comparable with the diffusion-controlled limit. The tyrosine triad (Tyr14.Tyr55.Tyr30) forming a hydrogen-bond network in the apolar active site of KSI has been characterized in an effort to identify the roles of the phenyl rings in catalysis, stability, and unfolding of the enzyme. The replacement of Tyr14, a catalytic residue, with serine resulted in a 33-fold decrease of kcat, while the replacements of Tyr30 and Tyr55 with serine decreased kcat by 4- and 51-fold, respectively. The large decrease of kcat for Y55S could be due to the structural perturbation of alpha-helix A3, which results in the reorientation of the active-site residues as judged by the crystal structure of Y55S determined at 2.2 A resolution. Consistent with the analysis of the Y55S crystal structure, the far-UV circular dichroism spectra of Y14S, Y30S, and Y55S indicated that the elimination of the phenyl ring of the tyrosine reduced significantly the content of alpha-helices. Urea-induced equilibrium unfolding experiments revealed that the DeltaG(U)H2O values of Y14S, Y30S, and Y55S were significantly decreased by 11.9, 13.7, and 9.5 kcal/mol, respectively, as compared with that of the wild type. A characterization of the unfolding kinetics based on PhiU-value analysis indicates that the interactions mediated by the tyrosine triad in the native state are very resistant to unfolding. Taken together, our results demonstrate that the internal packing by the phenyl rings in the active-site tyrosine triad contributes to the conformational stability and catalytic activity of KSI by maintaining the structural integrity of the alpha-helices.

Ultrathin single-crystalline silver nanowire arrays formed in an ambient solution phase.

We report the synthesis of single-crystalline silver nanowires of atomic dimensions. The ultrathin silver wires with 0.4 nanometer width grow up to micrometer-scale length inside the pores of self-assembled calix[4]hydroquinone nanotubes by electro-/photochemical redox reaction in an ambient aqueous phase. The present subnanowires are very stable under ambient air and aqueous environments, unlike previously reported metal wires of approximately 1 nanometer diameter, which existed only transiently in ultrahigh vacuum. The wires exist as coherently oriented three-dimensional arrays of ultrahigh density and thus could be used as model systems for investigating one-dimensional phenomena and as nanoconnectors for designing nanoelectronic devices.

Pseudoreversion of the catalytic activity of Y14F by the additional substitution(s) of tyrosine with phenylalanine in the hydrogen bond network of delta 5-3-ketosteroid isomerase from Pseudomonas putida biotype B.

Delta5-3-ketosteroid isomerase (KSI) from Pseudomonas putida Biotype B catalyzes the allylic isomerization of Delta5-3-ketosteroids to their conjugated Delta4-isomers via a dienolate intermediate. Two electrophilic catalysts, Tyr-14 and Asp-99, are involved in a hydrogen bond network that comprises Asp-99 Odelta2...O of Wat504...Tyr-14 Oeta...Tyr-55 Oeta.Tyr-30 Oeta in the active site of P. putida KSI. Even though neither Tyr-30 nor Tyr-55 plays an essential role in catalysis by the KSI, the catalytic activity of Y14F could be increased ca. 26-51-fold by the additional Y30F and/or Y55F mutation in the hydrogen bond network. To identify the structural basis for the pseudoreversion in the KSI, crystal structures of Y14F and Y14F/Y30F/Y55F have been determined at 1.8 and 2.0 A resolution, respectively. Comparisons of the two structures near the catalytic center indicate that the hydrogen bond between Asp-99 Odelta2 and C3-O of the steroid, which is perturbed by the Y14F mutation, can be partially restored to that in the wild-type enzyme by the additional Y30F/Y55F mutations. The kinetic parameters of the tyrosine mutants with the additional D99N or D99L mutation also support the idea that Asp-99 contributes to catalysis more efficiently in Y14F/Y30F/Y55F than in Y14F. In contrast to the catalytic mechanism of Y14F, the C4 proton of the steroid substrate was found to be transferred to the C6 position in Y14F/Y30F/Y55F with little exchange of the substrate 4beta-proton with a solvent deuterium based on the reaction rate in D2O. Taken together, our findings strongly suggest that the improvement in the catalytic activity of Y14F by the additional Y30F/Y55F mutations is due to the changes in the structural integrity at the catalytic site and the resulting restoration of the proton-transfer mechanism in Y14F/Y30F/Y55F.

Perforated peptic ulcer: a deliberative approach.

Between 1966 and 1987, 116 patients with 119 episodes of perforation were admitted to Box Hill Hospital into one surgical unit, and 91 patients with 92 episodes were admitted into the other, with patients being admitted in alternate weeks. In the former unit, in order to avoid surgery in those patients whose ulcers had sealed spontaneously, a deliberative approach was followed according to a strict protocol--involving a deliberate time delay in surgical decision-making. In the latter unit, a more conventional approach was adopted, and patients in that unit are used as a retrospective comparison. In the first unit, of 115 episodes which followed the protocol, six were unresuscitable, 15 needed immediate surgery and 94 followed a delayed approach. Of that 94, 12 needed surgery at 4-6 h, and a further eight needed later surgery. Seventy-four (68% of 'operable' patients) did not require corrective surgery at all, for their episode of perforation. The operable mortality rate was lower (6% compared with 13%), the bedstay was shorter, the prolonged bedstay rate was lower, and the morbidity was no worse, than those patients treated more conventionally in the second unit.

Potential organ or tumor imaging agents XV: radioiodinated phenytoin derivatives.

Three radioiodinated phenytoin analogs were synthesized, and tissue distribution studies were conducted in rats. Except for a greater retention of radioactivity following administration of the radioiodinated derivatives, the tissue distribution patterns were qualitatively similar to those found for 14C phenytoin. In nearly all cases, the adrenals, heart, kidneys, and liver displayed the greatest capacity to retain radioactivity. The high uptake of radioactivity observed for the thyroid was attributed to in vivo metabolic deiodination of the radioiodinated derivatives.