Identification of TMCO2 as an acrosome‐associated protein during rat spermiogenesis

We isolated the transmembrane and coiled‐coil domains 2 (Tmco2) gene using a polymerase chain reaction‐based subtraction technique. Tmco2 is predominantly expressed in rat testes starting from 4 weeks of age. Rat TMCO2 consists of 187 amino acids with a predicted molecular mass of 20.6 kDa. When expressed in COS7 cells, TMCO2 was found as vesicle‐like structures in the cytoplasm, whereas TMCO2ΔTM lacking the transmembrane (TM) region was found diffused in the cytoplasm. These results suggest that the TM region in TMCO2 is essential for its specificity of localization. Immunocytochemical analyzes indicated that rat TMCO2 was localized as small semiluminate bodies or cap‐like structures in the vicinity of round spermatid nuclei and as curved lines associated with nuclei of elongated spermatids and caput epididymal spermatozoa. However, it was detected in only a small part of cauda epididymal spermatozoa. Double immunolabeling of the spermatids and spermatozoa with the anti‐TMCO2 antibody and the monoclonal anti‐MN7 antibody showed that TMCO2 was predominantly associated with the inner acrosomal membrane in spermatids and caput epididymal spermatozoa. Our findings suggest that TMCO2 might be involved in the process of acrosome biogenesis, especially binding of acrosome to a nucleus, during spermiogenesis.     

Protein acetylation on 2-isopropylmalate synthase from Thermus thermophilus HB27

Extremophiles - Protein lysine Nε-acetylation is one of the important factors regulating cellular metabolism. We performed a proteomic analysis to identify acetylated proteins in the extremely...     

Effect of dietary fish oil on mouse testosterone level and the distribution of eicosapentaenoic acid-containing phosphatidylcholine in testicular interstitium

Low levels of serum testosterone are characteristically associated with diabetes, coronary atherosclerosis, obstructive sleep apnea, rheumatoid arthritis, and chronic obstructive pulmonary disease. Testosterone replacement therapy is effective against many of these disorders, indicating the importance of maintaining a healthy testosterone level. In this study, we investigated the effects of fish oil on murine testosterone metabolism and analyzed the dynamics of relevant lipids in testes by matrix-assisted laser desorption ionization mass spectrometry imaging. Testosterone was upregulated in mice that received fish oil. In the testicular interstitium, eicosapentaenoic acid-containing phosphatidylcholine was distributed characteristically. These data suggest that eicosapentaenoic acid is involved in testosterone metabolism.     

Generalizable brain network markers of major depressive disorder across multiple imaging sites

Many studies have highlighted the difficulty inherent to the clinical application of fundamental neuroscience knowledge based on machine learning techniques. It is difficult to generalize machine learning brain markers to the data acquired from independent imaging sites, mainly due to large site differences in functional magnetic resonance imaging. We address the difficulty of finding a generalizable marker of major depressive disorder (MDD) that would distinguish patients from healthy controls based on resting-state functional connectivity patterns. For the discovery dataset with 713 participants from 4 imaging sites, we removed site differences using our recently developed harmonization method and developed a machine learning MDD classifier. The classifier achieved an approximately 70% generalization accuracy for an independent validation dataset with 521 participants from 5 different imaging sites. The successful generalization to a perfectly independent dataset acquired from multiple imaging sites is novel and ensures scientific reproducibility and clinical applicability.

Biomarkers for psychiatric disorders based on neuroimaging data have yet to be put to practical use. This study overcomes the problems of inter-site differences in fMRI data by using a novel harmonization method, thereby successfully constructing a generalizable brain network marker of major depressive disorder across multiple imaging sites.     

Non-fibrillar amyloid-β peptide reduces NMDA-induced neurotoxicity, but not AMPA-induced neurotoxicity

Amyloid-β peptide (Aβ) is thought to be linked to the pathogenesis of Alzheimer’s disease. Recent studies suggest that Aβ has important physiological roles in addition to its pathological roles. We recently demonstrated that Aβ42 protects hippocampal neurons from glutamate-induced neurotoxicity, but the relationship between Aβ42 assemblies and their neuroprotective effects remains largely unknown. In this study, we prepared non-fibrillar and fibrillar Aβ42 based on the results of the thioflavin T assay, Western blot analysis, and atomic force microscopy, and examined the effects of non-fibrillar and fibrillar Aβ42 on glutamate-induced neurotoxicity. Non-fibrillar Aβ42, but not fibrillar Aβ42, protected hippocampal neurons from glutamate-induced neurotoxicity. Furthermore, non-fibrillar Aβ42 decreased both neurotoxicity and increases in the intracellular Ca²⁺ concentration induced by N-methyl-d-aspartate (NMDA), but not by α-amino-3-hydrozy-5-methyl-4-isoxazole propionic acid (AMPA). Our results suggest that non-fibrillar Aβ42 protects hippocampal neurons from glutamate-induced neurotoxicity through regulation of the NMDA receptor.