The development of disease-modifying therapies for Alzheimer’s disease (AD) is an urgent issue. Progress in the understanding of AD pathophysiology based on the amyloid hypothesis has led to the development of numerous candidate disease-modifying therapies over the past 15 years. The therapeutic target, amyloid β (Aβ), starts to accumulate in AD brains long before the onset of cognitive decline. γ-secretase inhibitors, γ-secretase modulators, and β-secretase inhibitors aim to reduce the production of toxic Aβ species by modifying the processing of amyloid precursor protein. Another strategy is to eliminate accumulated Aβ by active or passive immunotherapeutic approaches. Therapeutic strategies targeting tau protein are also currently emerging. Despite these efforts, successful disease-modifying therapies for AD have not yet been developed. Recently, very early interventional trials targeting preclinical stages of AD have begun; the paradigm shift in AD therapies from cure to prevention could be key to the success of disease modification.
Non-invasive and readily implemented in the clinical setting, eye movement studies have been conducted extensively not only in healthy human subjects but also in patients with neurological disorders. The purpose of saccade studies is to “read out” the pathophysiology underlying neurological disorders from the saccade records, referring to known primate physiology. In the current review, we provide an overview of studies in which we attempted to elucidate the patterns of saccade abnormalities in over 250 patients with neurological disorders, including cerebellar ataxia and brainstem pathology due to neurodegenerative disorders, and what they tell about the pathophysiology of patients with neurological disorders. We also discuss how interventions, such as deep brain stimulation, affect saccade performance and provide further insights into the workings of the oculomotor system in humans. Finally, we argue that it is important to understand the functional significance and behavioral correlate of saccade abnormalities in daily life, which could require eye tracking methodologies to be performed in settings similar to daily life.
For reliable transmission at chemical synapses, neurotransmitters must be released dynamically in response to neuronal activity in the form of action potentials. Stable synaptic transmission is dependent on the efficacy of transmitter release and the rate of resupplying synaptic vesicles to their release sites. Accurate regulation is conferred by proteins sensing Ca2+ entering through voltage-gated Ca2+ channels opened by an action potential. Presynaptic Ca2+ concentration changes are dynamic functions in space and time, with wide fluctuations associated with different rates of neuronal activity. Thus, regulation of transmitter release includes reactions involving multiple Ca2+-dependent proteins, each operating over a specific time window. Classically, studies of presynaptic proteins function favored large invertebrate presynaptic terminals. I have established a useful mammalian synapse model based on sympathetic neurons in culture. This review summarizes the use of this model synapse to study the roles of presynaptic proteins in neuronal activity for the control of transmitter release efficacy and synaptic vesicle recycling.
This study aimed to evaluate the residual radioactivity in mice induced by neutron irradiation with an accelerator-based boron neutron capture therapy (BNCT) system using a solid Li target. The radionuclides and their activities were evaluated using a high-purity germanium (HP-Ge) detector. The saturated radioactivity of the irradiated mouse was estimated to assess the radiation protection needs for using the accelerator-based BNCT system. 24Na, 38Cl, 80mBr, 82Br, 56Mn, and 42K were identified, and their saturated radioactivities were (1.4 ± 0.1) × 102, (2.2 ± 0.1) × 101, (3.4 ± 0.4) × 102, 2.8 ± 0.1, 8.0 ± 0.1, and (3.8 ± 0.1) × 101 Bq/g/mA, respectively. The 24Na activation rate at a given neutron fluence was found to be consistent with the value reported from nuclear-reactor-based BNCT experiments. The induced activity of each nuclide can be estimated by entering the saturated activity of each nuclide, sample mass, irradiation time, and proton current into the derived activation equation in our accelerator-based BNCT system.
Volvocine algae constitute a green algal lineage comprising unicellular Chlamydomonas, four-celled Tetrabaena, eight to 32-celled Gonium, and others up to Volvox spp., which consist of up to 50,000 cells. These algae proliferate by multiple fissions with cellular growth up to several fold in size and subsequent successive cell divisions. Chlamydomonas reinhardtii cells produce two to 32 daughter cells by one to five divisions, depending on cellular growth in the G1 phase. By contrast, in this study, we found that Tetrabaena socialis and Gonium pectorale cells mostly produced four and eight daughter cells by two and three successive divisions, respectively. In contrast to C. reinhardtii, which is committed to cell division when the cell has grown two-fold, T. socialis and G. pectorale are committed only when the cells have grown four- and eight-fold, respectively. Thus, our results suggest that evolutionary changes in cellular size for commitment largely contributes to the emergence and evolution of multicellularity in volvocine algae.
The double minimum potential (DMP), which Hund assumed to explain the quantum-mechanical stability of enantiomers, was discussed, by citing three typical examples of DMP: inversion, internal rotation, and puckering. They expanded the classical scope of chirality, as defined by Kelvin, and indicated that a new bridge could be formed between the three low-frequency DMP modes and the asymmetric syntheses of chiral molecules.