Jahn-Teller Inactivity and Magnetic Frustration in GeCo2_2O4_4 Probed by Ultrasound Velocity Measurements

Ultrasound velocity measurements of cubic spinel GeCo$_2$O$_4$ in single crystal were performed for the investigation of shear and compression moduli. The shear moduli in the paramagnetic state reveal an absence of Jahn-Teller activity despite the presence of orbital degeneracy in the Co$^{2+}$ ions. Such a Jahn-Teller inactivity indicates that the intersite orbital-orbital interaction is much stronger than the Jahn-Teller coupling. The compression moduli in the paramagnetic state near the N$\acute{e}$el temperature $T_N$ reveal that the most relevant exchange path for the antiferromagnetic transition lies in the [111] direction. This exchange-path anisotropy is consistent with the antiferromagnetic structure with the wave vector $q \parallel$ [111], suggesting the presence of bond frustration due to competition among a direct ferromagnetic and several distant-neighbors antiferromagnetic interactions. In the JT-inactive condition, the bond frustration can be induced by geometrical orbital frustration of $t_{2g}$-$t_{2g}$ interaction between the Co$^{2+}$ ions which can be realized in the pyrochlore lattice of the high spin Co$^{2+}$ with $t_{2g}$-orbital degeneracy. In GeCo$_2$O$_4$, the tetragonal elongation below $T_N$ releases the orbital frustration by quenching the orbital degeneracy.Comment: 7 pages, 7figures, to appear in Phys. Rev.

Na, K-ATPase α3 is a death target of Alzheimer patient amyloid-β assembly

Neurodegeneration correlates with Alzheimer's disease (AD) symptoms, but the molecular identities of pathogenic amyloid β-protein (Aβ) oligomers and their targets, leading to neurodegeneration, remain unclear. Amylospheroids (ASPD) are AD patient-derived 10- to 15-nm spherical Aβ oligomers that cause selective degeneration of mature neurons. Here, we show that the ASPD target is neuron-specific Na(+)/K(+)-ATPase α3 subunit (NAKα3). ASPD-binding to NAKα3 impaired NAKα3-specific activity, activated N-type voltage-gated calcium channels, and caused mitochondrial calcium dyshomeostasis, tau abnormalities, and neurodegeneration. NMR and molecular modeling studies suggested that spherical ASPD contain N-terminal-Aβ-derived "thorns" responsible for target binding, which are distinct from low molecular-weight oligomers and dodecamers. The fourth extracellular loop (Ex4) region of NAKα3 encompassing Asn(879) and Trp(880) is essential for ASPD-NAKα3 interaction, because tetrapeptides mimicking this Ex4 region bound to the ASPD surface and blocked ASPD neurotoxicity. Our findings open up new possibilities for knowledge-based design of peptidomimetics that inhibit neurodegeneration in AD by blocking aberrant ASPD-NAKα3 interaction

Current status of Neisseria gonorrhoeae cervicitis in pregnant women in Japan.

We evaluated the current prevalence of gonococcal cervicitis among pregnant women in institutes that either do or do not routinely screen for gonococcal infection in Japan. We requested 2,330 obstetrical facilities to provide information on Neisseria gonorrhoeae cervicitis in pregnant women. A total of 1,876 (80.5%) of them responded. The universal screening test for gonococcal cervicitis, involving nucleic acid amplification for all pregnant women, was performed in 281 institutes (13.9% of institutes across Japan). The total rate of pregnant women with gonococcal cervicitis was 1.3% in the institutes performing the screening test during pregnancy, while it was only 0.2% (p < 0.01) in those not performing it. This suggests that 84% of infected women may have been missed in the institutes that do not routinely perform the screening test for gonococcal cervicitis. It may be time to examine the cost-effectiveness of providing gonococcal screening for all pregnant women in Japan

Current status of cervical cytology during pregnancy in Japan.

In Japan, uterine cancer screening during pregnancy is subsidized by public funds. We examined the current status of the results of cervical cytology conducted during pregnancy in Japan. We requested 2,293 obstetrical facilities to provide information on cervical cytology in pregnant women who delivered between October 2018 and March 2019. A total of 1,292 obstetrical facilities responded, with valid information on a total of 238,743 women. The implementation rate of cervical cytology during pregnancy was 86.8% in Japan. The prevalence of abnormal cervical cytology during pregnancy was 3.3% in total and 4.9% using a spatula/brush with liquid-based cytology (LBC). The prevalence of positive high-risk human papillomavirus (HPV) in teenagers with atypical squamous cells of undetermined significance (ASC-US) was significantly higher than women of other ages (p < 0.01). Because HPV vaccine coverage has dropped to less than 1% in Japan, a further study with various conditions will be needed to improve the accuracy of cervical cancer screening during pregnancy

Alzheimer Aβ Assemblies Accumulate in Excitatory Neurons upon Proteasome Inhibition and Kill Nearby NAKα3 Neurons by Secretion

アルツハイマー病の神経毒性物質の形成と伝搬機構を解明 --発症に繋がる新たなメカニズムを提案--. 京都大学プレスリリース. 2019-03-01.We identified ∼30-mer amyloid-β protein (Aβ) assemblies, termed amylospheroids, from brains of patients with Alzheimer disease (AD) as toxic entities responsible for neurodegeneration and showed that Na+, K+-ATPase α3 (NAKα3) is the sole target of amylospheroid-mediated neurodegeneration. However, it remains unclear where in neurons amylospheroids form and how they reach their targets to induce neurodegeneration. Here, we present an in vitro culture system designed to chronologically follow amylospheroid formation in mature neurons expressing amyloid precursor protein bearing early-onset AD mutations. Amylospheroids were found to accumulate mainly in the trans-Golgi network of excitatory neurons and were initially transported in axons. Proteasome inhibition dramatically increased amylospheroid amounts in trans-Golgi by increasing Aβ levels and induced dendritic transport. Amylospheroids were secreted and caused the degeneration of adjacent NAKα3-expressing neurons. Interestingly, the ASPD-producing neurons later died non-apoptotically. Our findings demonstrate a link between ASPD levels and proteasome function, which may have important implications for AD pathophysiology