Klotho overexpression protects against renal aging along with suppression of transforming growth factor-ß1 signaling pathways.

Klotho is an antiaging protein reported to suppress transforming growth factor-ß1 (TGF-ß1) signaling. Aging kidneys are characterized by interstitial fibrosis, accumulation of cell cycle-arrested cells, and increased levels of oxidative stress. TGF-ß1 signaling is involved in these processes. In this study, we investigated whether klotho overexpression improves these features in the kidneys of aging mice and examined the inhibitory effect of klotho on signaling molecules related to transforming growth of TGF-ß1. Klotho transgenic (KLTG) and wild-type (WT) mice were used, and 8-wk-old and 24-mo-old mice were defined as young and aging, respectively. We found that klotho expression was decreased in aging WT mice, but it was maintained in aging KLTG mice. Klotho overexpression improved the survival of 24-mo-old mice. Although the serum Ca2+ level was significantly lower in aging KLTG mice than in aging WT mice, the serum phosphate level did not differ between these mice. Klotho overexpression attenuated the increases in blood pressure, serum blood urea nitrogen level, and serum creatinine level in aging mice. Interstitial fibrosis, accumulation of cell cycle-arrested cells, and oxidative stress did not differ between young KLTG and WT mice, but they were significantly suppressed in aging KLTG mice compared with aging WT mice. Furthermore, the expression of TGF-ß1-related signaling molecules was increased in aging WT mice, whereas it was inhibited in aging KLTG mice. These data suggest that klotho overexpression protects against kidney aging along with suppression of TGF-ß1 signaling pathways.NEW & NOTEWORTHY Klotho is considered as an antiaging protein, and its overexpression may be a candidate therapy for protection against kidney damage with advanced aging. Although multiple factors are involved in the aging process, we showed that klotho overexpression inhibited interstitial fibrosis, accumulation of cell cycle-arrested cells, and increased levels of oxidative stress in the kidneys of aging mice, suppressing transforming growth factor-ß1-related signaling pathways. The present data showed that klotho overexpression protects against age-associated kidney damage.

Selective adaptation in sentence comprehension: Evidence from event-related brain potentials.

In this study, two event-related potential experiments were conducted to investigate whether readers adapt their expectations to morphosyntactically (Experiment 1) or semantically (Experiment 2) anomalous sentences when they are repeatedly exposed to them. To address this issue, we experimentally manipulated the probability of occurrence of grammatical sentences and syntactically and semantically anomalous sentences through experiments. For the low probability block, anomalous sentences were presented less frequently than grammatical sentences (with a ratio of 1 to 4), while they were presented as frequently as grammatical sentences in the equal probability block. Experiment 1 revealed a smaller P600 effect for morphosyntactic violations in the equal probability block than in the low probability block. Linear mixed-effects models were used to examine how the size of the P600 effect changed as the experiment went along. The results showed that the smaller P600 effect of the equal probability block resulted from an amplitude's decline in morphosyntactically violated sentences over the course of the experiment, suggesting an adaptation to morphosyntactic violations. In Experiment 2, semantically anomalous sentences elicited a larger N400 effect than their semantically natural counterparts regardless of probability manipulation. Little evidence was found in favour of adaptation to semantic violations in that the processing cost associated with the N400 did not decrease over the course of the experiment. Therefore, a dynamic aspect of language-processing system was demonstrated in this study. We will discuss why the language-processing system shows a selective adaptation to morphosyntactic violations.

Inter-participant variabilities and sample sizes in P300 and P600.

Reliably and efficiently detecting physiological differences between conditions of interest is of importance in psychophysiology. In particular, when it comes to the observation of relatively small differences, such as a P600 effect, a language-related brain potential elicited by ungrammatical sentences compared to grammatical sentences, inter-participant variability is a critical factor since a larger inter-participant variability decreases statistical significance, and therefore increases the necessary sample size. The present study investigated how stable individual P600s are, at which sample sizes the P600 becomes stable, and how many participants are necessary to observe a P600 effect. P600s were recorded from 48 participants, as well as P300 (P3b) from 40 participants for comparison. Unlike the P3b effect, which had an approximately 10 µV difference between the target and standard stimuli, P600 increased in amplitude by only 1.4-1.7 µV at Pz during the processing of ungrammatical sentences relative to the grammatical counterparts. The sample size analysis suggests that 20 to 30 participants are needed to detect a P600 effect at Pz, and the distribution of variances does not change significantly with a larger sample size.

Coexistence of a clear cell adenocarcinoma and an adenosarcoma with a heterologous rhabdomyosarcoma in an endometriotic cyst of the ovary: a case study.

SUMMARY: A rare case of a clear cell adenocarcinoma and an adenosarcoma coexisting with a heterologous rhabdomyosarcoma in an endometriotic cyst of the ovary is reported. The tumor was composed of a cystic area and a solid area arising from the cyst wall. In the cystic lesion, a detached polypoid mass was also identified. The cyst wall was lined with a single layer of endometrial-type cells, whereas the solid area was composed of a clear cell adenocarcinoma. In the detached polypoid mass, an exophytic leaf-like pattern containing benign endometrial-type cells and squamous epithelial and rhabdomyosarcoma components, which were positive for desmin and myoglobin, was observed. Using X-chromosomal clonality assay, these clear cell adenocarcinoma and adenosarcoma components showed patterns of polyclonality. To the authors' knowledge, this is the first reported case of a clear cell adenocarcinoma and an adenosarcoma coexisting with heterologous rhabdomyosarcoma in an endometriotic cyst of the ovary.

Monoclonality of composite large cell neuroendocrine carcinoma and mucinous epithelial tumor of the ovary: a case study.

A rare case of mixed carcinoma of the ovary is reported, composed of a large cell neuroendocrine carcinoma and a mucinous borderline endocervical tumor. The large cell neuroendocrine carcinoma was composed of solid nests, sheets, and trabeculae of medium to large-sized cells, and was positive for synaptophysin. The mucinous epithelial tumor varied in appearance from a borderline to an intraepithelial carcinoma, and showed sparsely scattered immunoreactivity for chromogranin-A. Using an X-chromosome clonality assay, these 2 components showed patterns of monoclonality. These results suggest that the large cell neuroendocrine carcinoma may have arisen from the mucinous epithelial tumor.