Since 1965, the stereoselectivity in azoalkane denitrogenation has attracted much attention in both synthetic organic chemistry and physical organic chemistry. In this paper, a short review of the ...recent findings on the mechanism underlying the fascinating stereoselectivity in azoalkane denitrogenation is presented. The two types of singlet diradicals, i.e. the puckered and planar conformations, were found to play important roles in the stereoselectivity in the photochemical denitrogenation of cyclic azoalkanes. The presence of the puckered singlet diradical, which is the third isomer in homolysis, resolves the mechanistic puzzle reported so far for the stereoselectivity in azoalkane denitrogenations.
The termination mechanism of radical polymerization, that is, disproportionation (Disp) versus combination (Comb), determines the chain length and end‐group structure of the resulting polymer as well ...as polymer properties, and yet factors governing the mechanism are still unclear. Furthermore, no attempts have been made to control the mechanism. Here, the effects of temperature and viscosity on the termination of methyl methacrylate (MMA) and styrene (St) polymerization were elucidated by using small molecular model‐radicals and the corresponding polymer radicals in various solvents. The results showed that Disp was preferred over Comb if the temperature was decreased and the viscosity of the media was increased for all the radicals examined. Although the temperature effect on the Disp/Comb selectivity is counterintuitive because Disp should be favored entropically over Comb considering the decrease in the number of polymer chains in Comb, the results clearly showed that the observed inverse temperature effect was a result of the viscosity effect. Disp was favored over Comb at lower temperatures and in more viscous solvents because the transition state leading to Disp is more flexible than that for Comb. Because of the significant viscosity effect, Disp selectively occurred in highly viscous solvents; the Disp/Comb selectivity was 97/3 in both MMA and St termination. For the first time, the termination mechanism was intentionally controlled and such a high Disp selectivity was observed. In particular, the termination mechanism in St is described as Comb in textbooks, but nearly complete inversion of the selectivity from Comb to Disp is realized by simply changing the viscosity of the media.
Viscosity exhibition: The termination mechanism in radical polymerization (i.e., disproportionation versus combination) determines the chain length and end‐group structure of the resulting polymer as well as polymer properties, and can be controlled by the viscosity of the solvent. A polystyrene‐end radical undergoes combination in low‐viscosity media, but it selectively undergoes disproportionation in highly viscous media.
Although there is a substantial amount of data on the clinical characteristics, diagnostic criteria, and pathogenesis of myelin oligodendrocyte glycoprotein (MOG) autoantibody-associated disease ...(MOGAD), there is still uncertainty regarding the MOG protein function and the pathogenicity of anti-MOG autoantibodies in this disease. It is important to note that the disease characteristics, immunopathology, and treatment response of MOGAD patients differ from those of anti-aquaporin 4 antibody-positive neuromyelitis optica spectrum disorders (NMOSDs) and multiple sclerosis (MS). The clinical phenotypes of MOGAD are varied and can include acute disseminated encephalomyelitis, transverse myelitis, cerebral cortical encephalitis, brainstem or cerebellar symptoms, and optic neuritis. The frequency of optic neuritis suggests that the optic nerve is the most vulnerable lesion in MOGAD. During the acute stage, the optic nerve shows significant swelling with severe visual symptoms, and an MRI of the optic nerve and brain lesion tends to show an edematous appearance. These features can be alleviated with early extensive immune therapy, which may suggest that the initial attack of anti-MOG autoantibodies could target the structures on the blood–brain barrier or vessel membrane before reaching MOG protein on myelin or oligodendrocytes. To understand the pathogenesis of MOGAD, proper animal models are crucial. However, anti-MOG autoantibodies isolated from patients with MOGAD do not recognize mouse MOG efficiently. Several studies have identified two MOG epitopes that exhibit strong affinity with human anti-MOG autoantibodies, particularly those isolated from patients with the optic neuritis phenotype. Nonetheless, the relations between epitopes on MOG protein remain unclear and need to be identified in the future.
Olig2 is indispensable for motoneuron and oligodendrocyte fate-specification in the pMN domain of embryonic spinal cords, and also involved in the proliferation and differentiation of several cell ...types in the nervous system, including neural progenitor cells (NPCs) and oligodendrocytes. However, how Olig2 controls these diverse biological processes remains unclear. Here, we demonstrated that a novel Olig2-binding protein, DEAD-box helicase 20 (Ddx20), is indispensable for the survival of NPCs and oligodendrocyte progenitor cells (OPCs). A central nervous system (CNS)-specific Ddx20 conditional knockout (cKO) demonstrated apoptosis and cell cycle arrest in NPCs and OPCs, through the potentiation of the p53 pathway in DNA damage-dependent and independent manners, including SMN complex disruption and the abnormal splicing of Mdm2 mRNA. Analyzes of Olig2 null NPCs showed that Olig2 contributed to NPC proliferation through Ddx20 protein stabilization. Our findings provide novel mechanisms underlying the Olig2-mediated proliferation of NPCs, via the Ddx20-p53 axis, in the embryonic CNS.
Kainate receptors (KARs) are members of the glutamate receptor family that regulate synaptic function in the brain. Although they are known to be associated with psychiatric disorders, how they are ...involved in these disorders remains unclear. KARs are tetrameric channels assembled from a combination of GluK1-5 subunits. Among these, GluK2 and GluK5 subunits are the major heteromeric subunits in the brain. To determine the functional similarities and differences between GluK2 and GluK5 subunits, we generated GluK2 KO and GluK5 KO mice on a C57BL/6N background, a well-characterized inbred strain, and compared their behavioral phenotypes. We found that GluK2 KO and GluK5 KO mice exhibited the same phenotypes in many tests, such as reduced locomotor activity, impaired motor function, and enhanced depressive-like behavior. No change was observed in motor learning, anxiety-like behavior, or sociability. Additionally, we identified subunit-specific phenotypes, such as reduced motivation toward their environment in GluK2 KO mice and an enhancement in the contextual memory in GluK5 KO mice. These results revealed that GluK2 and GluK5 subunits not only function in a coordinated manner but also have a subunit-specific role in regulating behavior. To summarize, we demonstrated subunit-specific and common behavioral effects of GluK2 and GluK5 subunits for the first time. Moreover, to the best of our knowledge, this is the first evidence of the involvement of the GluK5 subunit in the expression of depressive-like behavior and contextual memory, which strongly indicates its role in psychiatric disorders.
The spinal dorsal horn comprises heterogeneous neuronal populations, that interconnect with one another to form neural circuits modulating various types of sensory information. Decades of evidence ...has revealed that transcription factors expressed in each neuronal progenitor subclass play pivotal roles in the cell fate specification of spinal dorsal horn neurons. However, the development of subtypes of these neurons is not fully understood in more detail as yet and warrants the investigation of additional transcription factors. In the present study, we examined the involvement of the POU domain-containing transcription factor Brn3a in the development of spinal dorsal horn neurons. Analyses of Brn3a expression in the developing spinal dorsal horn neurons in mice demonstrated that the majority of the Brn3a-lineage neurons ceased Brn3a expression during embryonic stages (Brn3a-transient neurons), whereas a limited population of them continued to express Brn3a at high levels after E18.5 (Brn3a-persistent neurons). Loss of Brn3a disrupted the localization pattern of Brn3a-persistent neurons, indicating a critical role of this transcription factor in the development of these neurons. In contrast, Brn3a overexpression in Brn3a-transient neurons directed their localization in a manner similar to that in Brn3a-persistent neurons. Moreover, Brn3a-overexpressing neurons exhibited increased axonal extension to the ventral and ventrolateral funiculi, where the axonal tracts of Brn3a-persistent neurons reside. These results suggest that Brn3a controls the soma localization and axonal extension patterns of Brn3a-persistent spinal dorsal horn neurons.
The cytomatrix at the active zone-associated structural protein (CAST) and its homologue, named ELKS, being rich in glutamate (E), leucine (L), lysine (K), and serine (S), belong to a family of ...proteins that organize presynaptic active zones at nerve terminals. These proteins interact with other active zone proteins, including RIMs, Munc13s, Bassoon, and the β subunit of Ca
channels, and have various roles in neurotransmitter release. A previous study showed that depletion of CAST/ELKS in the retina causes morphological changes and functional impairment of this structure. In this study, we investigated the roles of CAST and ELKS in ectopic synapse localization. We found that the involvement of these proteins in ribbon synapse distribution is complex. Unexpectedly, CAST and ELKS, in photoreceptors or in horizontal cells, did not play a major role in ribbon synapse ectopic localization. However, depletion of CAST and ELKS in the mature retina resulted in degeneration of the photoreceptors. These findings suggest that CAST and ELKS play critical roles in maintaining neural signal transduction in the retina, but the regulation of photoreceptor triad synapse distribution is not solely dependent on their actions within photoreceptors and horizontal cells.
Localized singlet diradicals have attracted much attention, not only in the field of bond‐homolysis chemistry, but also in nonlinear optical materials. In this study, an extremely long lived ...localized singlet diradical was obtained by using a new molecular design strategy in which it is kinetically stabilized by means of a macrocycle that increases the molecular strain of the corresponding σ‐bonded compound. Notably, the lifetime of this diradical (14 μs) is two orders of magnitude longer than that of a standard singlet diradical without a macrocyclic structure (≈0.2 μs) at 293 K. The species is persistent below a temperature of 100 K. In addition to the kinetic stabilization of the singlet diradical, the spontaneous oxidation of its corresponding ring‐closed compound at 298 K produced oxygenated products under atmospheric conditions. Apparently, the “stretch effect” induced by the macrocyclic structure plays a crucial role in extending the lifetime of localized singlet diradicals and increasing the reactivity of their corresponding σ‐bonded compounds.
Lifetime stretched: A new kinetic stabilization (stretch) effect affecting the reactivity of localized singlet diradicals, which is induced by the presence of a macrocyclic ring that increases the molecular strain of the corresponding σ‐bonded compound (see figure), was examined. Extremely long‐lived singlet diradicals emerged in this study.
Ca
-dependent activator protein for secretion 2 (CAPS2) regulates dense-core vesicle (DCV) exocytosis to facilitate peptidergic and catecholaminergic transmitter release. CAPS2 deficiency in mice has ...mild neuronal effects but markedly impairs social behavior. Rare
alterations also occur in autism spectrum disorder, although whether CAPS2-mediated release influences social behavior remains unclear. Here, we demonstrate that CAPS2 is associated with DCV exocytosis-mediated release of the social interaction modulatory peptide oxytocin (OXT). CAPS2 is expressed in hypothalamic OXT neurons and localizes to OXT nerve projection and OXT release sites, such as the pituitary.
KO mice exhibited reduced plasma albeit increased hypothalamic and pituitary OXT levels, indicating insufficient release. OXT neuron-specific
conditional KO supported CAPS2 function in pituitary OXT release, also affording impaired social interaction and recognition behavior that could be ameliorated by exogenous OXT administered intranasally. Thus, CAPS2 appears critical for OXT release, thereby being associated with social behavior.
The role of the neuropeptide oxytocin in enhancing social interaction and social bonding behavior has attracted considerable public and neuroscientific attention. A central issue in oxytocin biology concerns how oxytocin release is regulated. Our study provides an important insight into the understanding of oxytocin-dependent social behavior from the perspective of the CAPS2-regulated release mechanism.
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