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Depression and anxiety are common psychiatric disorders that can occur throughout an individual’s lifetime. Numerous pathways underlying the onset of these diseases have been identified in rodents using a social defeat stress protocol, whereby socially defeated individuals exhibit depression- and/or anxiety-like phenotypes that typically manifest as social avoidance behavior. However, most studies in this field have been conducted using young adult mice; therefore, information about social defeat stress-related behavioral phenotypes in older mice is limited. In this study, we exposed groups of young adult (8–16 weeks old) and aged (24 months old) C57BL/6J mice to mild social defeat stress by challenging them with aggressive CD1 mice while restricting the intensity of aggression to protect the animals from severe injuries. We then identified stress-induced behavioral changes and compared their expression between the age groups and with a non-defeated (non-stressed) control group. We found that the stressed mice in both age groups exhibited similar reduced social interactions that were indicative of increased social avoidance behavior. Moreover, unlike the young stressed and control groups, only the aged stressed group showed a reduced preference for sucrose, which was correlated with social avoidance behavior. Also, the aged stressed mice exhibited an attenuated defeat-induced increase in water intake. These findings reveal that aging alters behavioral phenotypes after social defeat and that the hedonic behavior of aged mice is more vulnerable to social defeat compared with younger mice. [ABSTRACT FROM AUTHOR]

This study examined the effect of changes in body temperature during exercise on signal transduction-related glucose uptake in the skeletal muscle of type 2 diabetic rats. Otsuka Long-Evans Tokushima Fatty rats (25 weeks of age), which have type 2 diabetes, were divided into the following four weight-matched groups; control (CON, n = 6), exercised under warm temperature (WEx, n = 8), exercised under cold temperature (CEx, n = 8), and heat treatment (HT, n = 6). WEx and CEx animals were subjected to running on a treadmill at 20 m/min for 30 min under warm (25°C) or cold (4°C) temperature. HT animals were exposed to single heat treatment (40–41°C for 30 min) in a heat chamber. Rectal and muscle temperatures were measured immediately after exercise and heat treatment, and the gastrocnemius muscle was sampled under anesthesia. Rectal and muscle temperatures increased significantly in rats in the WEx and HT, but not the CEx, groups. The phosphorylation levels of Akt, AS160, and TBC1D1 (Thr590) were significantly higher in the WEx and HT groups than the CON group (p < 0.05). In contrast, the phosphorylation levels of AMP-activated protein kinase, ACC, and TBC1D1 (Ser660) were significantly higher in rats in the WEx and CEx groups than the CON group (p < 0.05) but did not differ significantly between rats in the WEx and CEx groups. Body temperature elevation by heat treatment did not activate the AMPK signaling. Our data suggest that body temperature elevation during exercise is essential for activating the Akt signaling pathway in the skeletal muscle of rats with type 2 diabetic rats. [ABSTRACT FROM AUTHOR]

Background: Bevacizumab (BEV), a humanized monoclonal antibody, become a currently important chemotherapeutic option for the patients with recurrent glioma. The aim of this retrospective study is to investigate whether 18F-Fluoromisonidazole (FMISO) PET have the potential to detect BEV-resistant gliomas in the early-stage. Methods: We reviewed the FMISO PET and MRI appearances before and 3 to 4 courses after BEV treatment on 18 recurrent glioma patients. FMISO accumulation was assessed by visual inspection and semi-quantitative values which were tumor-to-normal (T/N) ratio and hypoxic volume. MRI responses were evaluated based on RANO (Response Assessment in Neuro-Oncology) criteria. The prognostic analysis was performed in relation to the response assessment by FMISO PET and MRI using overall survival (OS) after BEV application. Results: After BEV application, MRI revealed partial response in 14 of 18 patients (78%), of which 9 patients also demonstrated decreased FMISO accumulation. These 9 patients (50%) were classified as “MRI-FMISO double responder”. As for the other 5 patients (28%), FMISO accumulation volumes increased or remained stable after BEV treatment although partial responses were achieved on MRI. Therefore, these cases were classified as “MRI-only responder”. The remaining 4 patients (22%) did not show treatment response on FMISO PET or MRI (“non-responder”). MRI-FMISO double responders showed significantly longer OS than that in other groups (median 12.4 vs 5.7 months; P < 0.001), whereas there were no overall survival difference between MRI-only responders and non-responders (median OS, 5.7 and 4.8 months; P = 0.58). Among the pre-treatment clinical factors, high FMISO T/N ratio was a significant prognostic factor of overall survival in these patients under the assessment of Cox proportional hazard model. Conclusions: Recurrent gliomas with decreasing FMISO accumulation after short-term BEV application could derive a survival benefit from BEV treatment. Change in FMISO PET appearance can identify BEV-resistant gliomas in early-stage regardless of MRI findings in a comprehensible way. [ABSTRACT FROM AUTHOR]

The chicken domestication process represents a typical model of artificial selection, and gives significant insight into the general understanding of the influence of artificial selection on recognizable phenotypes. Two Japanese domesticated chicken varieties, the fighting cock (Shamo) and the long-crowing chicken (Naganakidori), have been selectively bred for dramatically different phenotypes. The former has been selected exclusively for aggressiveness and the latter for long crowing with an obedient sitting posture. To understand the particular mechanism behind these genetic changes during domestication, we investigated the degree of genetic differentiation in the aforementioned chickens, focusing on dopamine receptor D2, D3, and D4 genes. We studied other ornamental chickens such as Chabo chickens as a reference for comparison. When genetic differentiation was measured by an index of nucleotide differentiation (NST) newly devised in this study, we found that the NST value of DRD4 for Shamo (0.072) was distinctively larger than those of the other genes among the three populations, suggesting that aggressiveness has been selected for in Shamo by collecting a variety of single nucleotide polymorphisms. In addition, we found that in DRD4 in Naganakidori, there is a deletion variant of one proline at the 24th residue in the repeat of nine prolines of exon 1. We thus conclude that artificial selection has operated on these different kinds of genetic variation in the DRD4 genes of Shamo and Naganakidori so strongly that the two domesticated varieties have differentiated to obtain their present opposite features in a relatively short period of time. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy for high-grade meningioma (HGM) is one of the essential treatment options for disease control. However, appropriate irradiation timing remains under debate. The object of this study is to discern which prognostic factors impact recurrence in HGM patients and to propose a risk-stratification system for the application of postoperative radiotherapy. Methods: We retrospectively reviewed 55 adult patients who were diagnosed with Grade II and III intracranial meningioma. Cox regression models were applied to the analysis for impact on early recurrence in HGM patients without postoperative radiotherapy. Results: Grade III malignancy (P = 0.0073) and transformed histology (P = 0.047) proved to be significantly poor prognostic factors of early recurrence by multivariate analysis. The other candidates for recurrence factors were Simpson Grade 3–5 resection, preoperative Karnofsky Performance status < = 70%, and MIB-1 labeling index > = 15%. According to these prognostic factors, postoperative HGM patients could be stratified into three recurrence-risk groups. The prognoses were significantly different between each group, as the 3-year actual recurrence-free rates were 90% in low-risk group, 31% in intermediate-risk group, and 15% in high-risk group. Conclusion: We propose recurrence-risk stratification for postoperative HGM patients using clinically available factors. Our results suggest that the prognosis for patients with high-risk HGMs is dismal, whereas HGM patients belonging to the low-risk group could have favorable prognoses. This stratification provides us with the criteria necessary to determine whether to apply adjuvant radiotherapy to postoperative HGM patients, and to also help identify potentially curable HGMs without adjuvant radiotherapy. [ABSTRACT FROM AUTHOR]