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The rnt-1 gene is the only Caenorhabditis elegans homologue of the mammalian RUNX genes. Several lines of molecular biological evidence have demonstrated that the RUNX proteins interact and cooperate with Smads, which are transforming growth factor-[beta] (TGF-[beta]) signal mediators. However, the involvement of RUNX in TGF-[beta] signaling has not yet been supported by any genetic evidence, The Sma/ Mab TGF-[beta] signaling pathway in C. elegans is known to regulate body length and male tail development. The rnt-1(ok351) mutants show the characteristic phenotypes observed in mutants of the Sma/Mab pathway, namely, they have a small body size and ray defects. Moreover, RNT-1 can physically interact with SMA-4 which is one of the Smads in C. elegans, and double mutant animals containing both the rnt-1(ok351) mutation and a mutation in a known Sma/Mab pathway gene displayed synergism in the aberrant phenotypes. In addition, lon-1(e185) mutants was epistatic to rnt-1(ok351) mutants in terms of long phenotype, suggesting that lon-1 is indeed downstream target of rnt-1. Our data reveal that RNT-1 functionally cooperates with the SMA-4 proteins to regulate body size and male tail development in C. elegans. Keywords: Sma/Mab pathway; dbl-1 pathway; Runt domain; PEBP2/CBF; TGF-[beta] signaling

Alzheimer's disease (AD) is a neurodegenerative disorder influenced by age, sex, genetic factors, immune alterations, and infections. Multiple lines of evidence suggest that changes in antibody response are linked to AD pathology. To elucidate the mechanisms underlying AD development, we investigated antibodies that target autoimmune epitopes using high-resolution epitope microarrays. Our study compared two groups: individuals with AD (n = 19) and non-demented (ND) controls (n = 19). To validate the results, we measured antibody levels in plasma samples from AD patients (n = 96), mild cognitive impairment (MCI; n = 91), and ND controls (n = 97). To further explore the invlovement of EBV, we performed epitope masking immunofluorescence microscopy analysis and tests to induce lytic replication using the B95–8 cell line. In this study, we analyzed high-resolution epitope-specific serum antibody levels in AD, revealing significant disparities in antibodies targeting multiple epitopes between the AD and control groups. Particularly noteworthy was the significant down-regulation of antibody (anti-DG#29) targeting an epitope of Epstein-Barr virus nuclear antigen 1 (EBNA1). This down-regulation increased AD risk in female patients (odds ratio up to 6.6), but not in male patients. Our investigation further revealed that the down-regulation of the antibody (anti-DG#29) is associated with EBV reactivation in AD, as indicated by the analysis of EBV VCA IgG or IgM levels. Additionally, our data demonstrated that the epitope region on EBNA1 for the antibody is hidden during the EBV lytic reactivation of B95–8 cells. Our findings suggest a potential relationship of EBV in the development of AD in female. Moreover, we propose that antibodies targeting the epitope (DG#29) of EBNA1 could serve as valuable indicators of AD risk in female. [ABSTRACT FROM AUTHOR]

Vacuolar H+-ATPases (V-ATPases) are ATP-dependent proton pumps localized at membranes of intracellular acidic organelles and plasma membranes of various cell types. By virtue of its regulation in acidification, V-ATPase is required for many intracellular processes such as receptor-mediated endocytosis and protein sorting. Here we report the molecular characterization of the E subunit of V-ATPase in Caenorhabditis elegans. This subunit is one of the most well conserved subunits sharing approximately 57% identity with the human homologue, ATP6E. Green fluorescent protein (GFP) and whole-mount immunostaining analyses showed that V-ATPase E subunit (vha-8) is abundantly expressed in the H-shaped excretory cell, consistent with the expression patterns observed for other V-ATPase subunits. Double-stranded RNAs (or RNAi) targeted to vha-8 resulted in embryonic and larval lethality for the first filial generation, indicating that vha-8 is essential during early developmental processes. In addition, accumulation of abnormal endomitotic oocytes and defects in receptor-mediated endocytosis were observed in parental animals. These findings suggest that multiple phenotypes caused by the disruption of pH homeostasis are due to the defective V-ATPase. In summary, vha-8 encoding the E subunit of V-ATPase in C. elegans is essential for embryogenesis and receptor-mediated endocytosis. [Copyright &y& Elsevier]

Meta-analyses have found a negative relationship between religiousness and IQ of around r = −0.2, including in samples of elderly Westerners. However, there have been few attempts to directly test the existence of the religion-IQ nexus in non-Western societies. We administered a cognitive test to a representative sample of elderly South Koreans who were also surveyed about their religion and tested whether elderly nonreligious people had higher mean IQ scores than elderly religious people. Using a broad cognitive test battery, we computed mean IQ scores of n = 589 non-religious, n = 494 Protestants, n = 520 Catholics, n = 347 Buddhists, and n = 17 Confucianists. Elderly South Koreans who claimed to have 'no religion' had lower mean IQs than religious Koreans. This finding is not consistent with previous findings from meta-analyses. We argue that it is explicable in terms of differences in how the concept of religion is understood when comparing Western and Northeast Asian societies. Many of the 'non-religious' category would be adherents to Korean folk religion, something expected to be associated with lower mean IQ. • There is a negative relationship between religiousness and IQ. • The relationship has not been tested in non-Western societies. • We tested a representative sample of elderly South Koreans. • Elderly non-religious persons had lower mean IQs than elderly religious persons. • The non-religious are most likely adherents to Korean folk religion. [ABSTRACT FROM AUTHOR]

The early diagnosis of Alzheimer's Disease (AD) plays a central role in the treatment of AD. Particularly, identifying the preclinical AD (pAD) stage could be crucial for timely treatment in the elderly. However, screening participants with pAD requires a series of psychological and neurological examinations. Thus, an efficient diagnostic tool is needed. Here, we recruited 91 elderly participants and collected 1 min of resting-state electroencephalography data to classify participants as normal aging or diagnosed with pAD. We used deep neural networks (Deep ConvNet, EEGNet, EEG-TCNet, and cascade CRNN) in the within- and cross-subject paradigms for classification and found individual variations of classification accuracy in the cross-subject paradigm. Further, we proposed an individualized diagnostic strategy to identify neurophysiological similarities across participants and the proposed approach considering individual characteristics improved the diagnostic performance by approximately 20%. Our findings suggest that considering individual characteristics would be a breakthrough in diagnosing AD using deep neural networks. [ABSTRACT FROM AUTHOR]

Abstract: β-Catenin is implicated in quite different cellular processes, which require a fine-tuned regulation of its function. Here we demonstrate that cyclin-dependent kinase 6 (CDK6), in association with cyclin D1 (CCND1), directly binds to β-catenin. We showed that CCND1-CDK6 phosphorylates β-catenin on serine 45 (S45). This phosphorylation creates a priming site for glycogen synthase kinase 3β (GSK3β) and is both necessary and sufficient to initiate the β-catenin phosphorylation–degradation cascade. Moreover, co-immunoprecipitation assays using Wnt3a-conditioned medium reveals that while Wnt stimulation leads to the dissociation of β-catenin from axin and casein kinase Iα (CKIα), Wnt treatment promotes an increase in CCND1 level and the association of β-catenin with CCND1-CDK6. Furthermore, Wnt3a-stimulated cytosolic β-catenin levels were higher in CDK6 knockout mouse embryonic fibroblasts (CDK6−/− MEFs) compared to wild-type MEFs. Thus, the CCND1-CDK6 complex is like to negatively regulate Wnt signaling by mediating β-catenin phosphorylation and its subsequent degradation in Wnt-stimulated cells. [Copyright &y& Elsevier]