Repression Effects of Hydrolysates from Hen-Egg Proteins on Amyloid Fibril Formation.

Amyloid fibrils, which are formed from aggregates of aberrant proteins, can cause various forms of amyloidosis (including Alzheimer's disease). Such disorders often occur in elderly populations and are suspected to be lifestyle related. Thus, it has been speculated that some foodstuffs could be beneficial for preventing amyloidosis.

Stability of hen egg-white lysozyme during embryonic development.

It is of interest to determine whether and how egg-white proteins are maintained in fertile eggs. We previously observed that egg-white ovalbumin attained high stability during embryogenesis. Herein, we observed that the total mass of egg white and that of its gross protein content showed a decrease according to the days of incubation.

Characterization of amylolytic enzyme overproducing mutant of Aspergillus luchuensis obtained by ion beam mutagenesis.

Aspergillus luchuensis is a kuro (black) koji fungus that has been used as a starch degrader for the awamori- and shochu-making industries in Japan. In this study, we investigated the effect of ion beam irradiation on A. luchuensis RIB2601 and obtained a high starch-degrading mutant strain U1.

Parainfluenza 3-Induced Cough Hypersensitivity in the Guinea Pig Airways.

The effect of respiratory tract viral infection on evoked cough in guinea pigs was evaluated. Guinea pigs were inoculated intranasally with either parainfluenza type 3 (PIV3) and cough was quantified in conscious animals. The guinea pigs infected with PIV3 (day 4) coughed nearly three times more than those treated with the viral growth medium in response to capsaicin, citric acid, and bradykinin.

Targeting voltage gated sodium channels NaV1.7, Na V1.8, and Na V1.9 for treatment of pathological cough.

Recent advances in our understanding of voltage-gated sodium channels (NaVs) lead to the rational hypothesis that drugs capable of selective blockade of NaV subtypes may be a safe and effective strategy for the treatment of unwanted cough. Among the nine NaV subtypes (NaV1.1-NaV1.

Selective inhibition of vagal afferent nerve pathways regulating cough using Nav 1.7 shRNA silencing in guinea pig nodose ganglia.

Adeno-associated virus delivery systems and short hairpin RNA (shRNA) were used to selectively silence the voltage-gated sodium channel NaV 1.7 in the nodose ganglia of guinea pigs. The cough reflex in these animals was subsequently assessed.

Selective silencing of Na(V)1.7 decreases excitability and conduction in vagal sensory neurons.

There has been much information learned in recent years about voltage gated sodium channel (Na(V)) subtypes in somatosensory pain signalling, but much less is known about the role of specific sodium channel subtypes in the vagal sensory system. In this study, we developed a technique using adeno-associated viruses (AAVs) to directly introduce shRNA against Na(V)1.7 subtype gene into the vagal sensory ganglia of guinea pigs in vivo.

Targeting peripheral afferent nerve terminals for cough and dyspnea.

Chronic unproductive coughing and dyspnea are symptoms that severely diminish the quality of life in a substantial proportion of the population. There are presently few if any drugs that effectively treat these symptoms. Rational drug targets for cough and dyspnea have emerged over the recent years based on developments in our understanding of the innervation of the respiratory tract.

Molecular mechanism of allosteric modification of voltage-dependent sodium channels by local anesthetics.

The hallmark of many intracellular pore blockers such as tetra-alkylammonium compounds and local anesthetics is their ability to allosterically modify the movement of the voltage sensors in voltage-dependent ion channels. For instance, the voltage sensor of domain III is specifically stabilized in the activated state when sodium currents are blocked by local anesthetics. The molecular mechanism underlying this long-range interaction between the blocker-binding site in the pore and voltage sensors remains poorly understood.

Molecular determinants of coupling between the domain III voltage sensor and pore of a sodium channel.

In a voltage-dependent sodium channel, the activation of voltage sensors upon depolarization leads to the opening of the pore gates. To elucidate the principles underlying this conformational coupling, we investigated a putative gating interface in domain III of the sodium channel using voltage-clamp fluorimetry and tryptophan-scanning mutagenesis. Most mutations have similar energetic effects on voltage-sensor activation and pore opening.

Distinct structural changes in the GABAA receptor elicited by pentobarbital and GABA.

The barbiturate pentobarbital binds to gamma-aminobutyric acid type A (GABA(A)) receptors, and this interaction plays an important role in the anesthetic action of this drug. Depending on its concentration, pentobarbital can potentiate (approximately 10-100 microM), activate (approximately 100-800 microM), or block (approximately 1-10 mM) the channel, but the mechanisms underlying these three distinct actions are poorly understood. To investigate the drug-induced structural rearrangements in the GABA(A) receptor, we labeled cysteine mutant receptors expressed in Xenopus oocytes with the sulfhydryl-reactive, environmentally sensitive fluorescent probe tetramethylrhodamine-6-maleimide (TMRM).

Local anesthetics disrupt energetic coupling between the voltage-sensing segments of a sodium channel.

Local anesthetics block sodium channels in a state-dependent fashion, binding with higher affinity to open and/or inactivated states. Gating current measurements show that local anesthetics immobilize a fraction of the gating charge, suggesting that the movement of voltage sensors is modified when a local anesthetic binds to the pore of the sodium channel. Here, using voltage clamp fluorescence measurements, we provide a quantitative description of the effect of local anesthetics on the steady-state behavior of the voltage-sensing segments of a sodium channel.

Local and global ligand-induced changes in the structure of the GABA(A) receptor.

Ligand-gated channels mediate synaptic transmission through conformational transitions triggered by the binding of neurotransmitters. These transitions are well-defined in terms of ion conductance, but their structural basis is poorly understood. To probe these changes in structure, GABA(A) receptors were expressed in Xenopus oocytes and labeled at selected sites with environment-sensitive fluorophores.