Schizophrenia is a devastating mental illness that can lead to deterioration in the social and occupational functioning of affected individuals with a major cost to society. A wide range of studies suggest a genetic component to the inheritance of schizophrenia. The molecular genetic studies on schizophrenia have been actively performed since late 1980s. In linkage studies, no loci were replicated across studies and there were no loci surpassing genome-wide significance. Candidate gene association studies showed generally inconsistent results and there were no enrichment of smaller P-values. In the GWAS era, the community has coalesced into large international consortia. The largest schizophrenia GWAS to date is 50,000 samples and efforts are ongoing to accumulate 50,000 cases and 50,000 controls as part of 'PGC2' collaboration. With the limitation of GWAS results, several alternatives are being explored. In genotyping, the concepts of allelic spectrum including from common polygenic to rare penetrant variation are emerging. Phenotypes include all phenomena beyond DNA. The developments in transcriptomic & proteomic approach and intensive research on endophenotype will bring crucial insights into the nature of schizophrenia in the future. But there still remains our task about research on many factors including environment that influence gene expression (epigenetics), age, and gender.
Cooperative Behavior ; DNA ; Endophenotypes ; Epigenomics ; Gene Expression ; Genetic Association Studies ; Molecular Biology ; Phenotype ; Schizophrenia ; Wills

Pathogenic microbes secrete various enzymes with lipolytic activities to facilitate their survival within the host. Lipolytic enzymes include extracellular lipases and phospholipases, and several lines of evidence have suggested that these enzymes contribute to the virulence of pathogenic fungi. Candida albicans and Cryptococcus neoformans are the most commonly isolated human fungal pathogens, and several biochemical and molecular approaches have identified their extracellular lipolytic enzymes. The role of lipases and phospholipases in the virulence of C. albicans has been extensively studied, and these enzymes have been shown to contribute to C. albicans morphological transition, colonization, cytotoxicity, and penetration to the host. While not much is known about the lipases in C. neoformans, the roles of phospholipases in the dissemination of fungal cells in the host and in signaling pathways have been described. Lipolytic enzymes may also influence the survival of the lipophilic cutaneous pathogenic yeast Malassezia species within the host, and an unusually high number of lipase-coding genes may complement the lipid dependency of this fungus. This review briefly describes the current understanding of the lipolytic enzymes in major human fungal pathogens, namely C. albicans, C. neoformans, and Malassezia spp.
Candida albicans ; Colon ; Complement System Proteins ; Cryptococcus neoformans ; Dependency (Psychology) ; Fungi ; Humans ; Lipase ; Malassezia ; Phospholipases ; Yeasts

Background: Locomotor activity in mice may have an ultradian rest-activity rhythm. However, to date, no study has shown how locomotor activity can be explained statistically using fitted cosine curves. Therefore, this study explored whether the ultradian rhythm of locomotor activity in mice could be analyzed using cosine fitting analysis. Methods: The locomotor activity of 20 male mice under a 12/12-hour dark/light cycle for 2 days was fitted to a cosine function to obtain the best fit. The mean absolute error (MAE) values were used to determine the explanatory power of the calculated cosine model for locomotor activity. The cosine fitting analysis was performed using R statistical software (version 4.1.1). Results: The mean MAE was 0.2944, whereas the mean MAE for integrating the individual analyses in the two experimental groups was 0.3284. The periods of the estimated ultradian rest-activity rhythm ranged from 1.602 to 4.168 hours. Conclusions These results suggest that locomotor activity data reflect an ultradian rhythm better than a circadian rhythm. Locomotor activity can be statistically fitted to a cosine curve under well-controlled conditions. In the future, it will be necessary to explore whether this cosine-fitting analysis can be used to analyze ultradian rhythms under different experimental conditions.

BACKGROUND: The International Agency for Research on Cancer (IARC) defined that asbestos is a group 1 substance that causes lung cancer, mesothelioma (pleura and peritoneum), laryngeal cancer, and ovarian cancer in humans. Many studies on lung cancer, and mesothelioma caused by asbestos exposure have been conducted, but there was no case report of ovarian cancer due to asbestos exposure in Korea. We describe a case of ovarian cancer caused by asbestos exposure in a worker who worked at an asbestos textile factory for 3 years and 7 months in the late 1970s. CASE PRESENTATION: A 57-year-old woman visited the hospital because she had difficulty urinating. Ovarian cancer was suspected in radiologic examination, and exploratory laparotomy was performed. She was diagnosed with epithelial ovarian cancer. The patient did not undergo postoperative chemotherapy and recovered. She joined the asbestos factory in March 1976 and engaged in asbestos textile twisting and spinning for 1 year, 2 years and 7 months respectively. In addition, she lived near the asbestos factory for more than 20 years. There was no other specificity or family history. CONCLUSION: Considering the patient’s occupational and environmental history, it is estimated that she had been exposed to asbestos significantly, so we determined that ovarian cancer in the patient is highly correlated with the occupational exposure of asbestos and environmental exposure is a possible cause as well. Social devices are needed to prevent further exposure to asbestos. It is also necessary to recognize that ovarian cancer can occur in workers who have previously been exposed to asbestos, and the education and social compensation for those workers are needed.
Asbestos ; Compensation and Redress ; Drug Therapy ; Education ; Environmental Exposure ; Female ; Humans ; International Agencies ; Korea ; Laparotomy ; Laryngeal Neoplasms ; Lung Neoplasms ; Mesothelioma ; Middle Aged ; Occupational Diseases ; Occupational Exposure ; Ovarian Neoplasms ; Sensitivity and Specificity ; Textile Industry ; Textiles

Objective: This study aimed to explore the relationship among several indices of circadian rhythms and lipid peroxidation of brain tissue in mice. Methods: After entrainment of 4-week-old mice, one group was disrupted their circadian rhythms for three days and the other group for seven days (n = 10, respectively). After a recovery period, the Y-maze test, the elevated plus maze test, the tail suspension test, and the forced swimming test were conducted. To assess lipid peroxidation in brain tissue, thiobarbituric acid reactive substances were measured in the cortex, hippocampus, and cerebellum. Results: When circadian rhythms were disrupted and adapted back to their original rhythm, the recovery time of the 7-day disruption group (median 3.35 days) was significiantly faster than one of the 3-day disruption group (median 4.87 days). In the group with a 7-day disruption, mice that had recovered their rhythms early had higher malondialdehyde levels in their hippocampus compared to those with delayed recovery. The entrainment of circadian rhythms was negatively correlated with the malondialdehyde level of brain tissue. The behavioral test results showed no differences depending on the disruption durations or recovery patterns of circadian rhythms. Conclusion These results suggest that disruption types, recovery patterns, and the entrainment of circadian rhythms are likely to affect oxidative stress in adolescents or young adult mice. Future study is needed to confirm and specify these results on the effects of circadian rhythms on oxidative stress and age-dependent effects.

Behavioral and psychological symptoms in dementia (BPSD) are one of the common causes leading to significant impairment in quality of life for both patients and their caregivers, as well as an increased risk of institutionalization. In the treatment of BPSD, the first step is to check medical illness, and environmental status that can cause BPSD. When BPSD are associated with medical illness or environmental status, it is important to correct this condition for treatment of BPSD. However, if BPSD are very severe enough to be dangerous to patients or others and are not treatable by nonpharmacological approaches, pharmacological treatments could be considered. In pharmacological approaches, it is important to select relevant drugs according to the target symptoms, such as psychosis, depression, agitation, sleep disturbance, and so on. Due to the altered pharmacokinetics and pharmacodynamics, drug dosages for the patients with dementia should be started very low and increased slowly.
Caregivers ; Dementia* ; Depression ; Dihydroergotamine ; Drug Therapy* ; Humans ; Institutionalization ; Pharmacokinetics ; Psychotic Disorders ; Quality of Life ; Resin Cements

OBJECTIVES: This study was designed to test the hypothesis that delayed recovery from disrupted circadian rhythm is associated with both manic and depressive episodes in bipolar disorder. METHODS: Twenty-two male mice (age of five weeks, weight 28–30 gm) underwent three days of light-dark cycle disruption and 10 days of recovery phase. Sleep and wake state were checked every five minutes during the entire experimental period. After recovery phase, quinpirole (0.5 mg/kg, s.c.) was injected into the mice and open field locomotor activities were checked. Five days after the open field test, immobility time during the last 4 min in 6 min of forced swimming test was measured. Animals which recovered sleep-wake cycle within six days after light-dark cycle disruption were assigned to the early recovery group (n=14), and those that failed to recover in six days were assigned to the delayed recovery group (n=8). The locomotor activities and the immobility times of the two groups were compared by Mann-Whiney U test at two-tailed significance level of 0.05. RESULTS: The locomotor activities of the delayed recovery group were higher (mean rank=16.19) than those of the early recovery group (mean rank=8.82, U=18.5, p=0.008). The immobility times did not differ by recovery time (U=32.0 p=0.110). CONCLUSION: The results suggest that delayed recovery from circadian rhythm disruption raises the risk of manic symptoms rather than depressive symptoms.
Animals ; Animals* ; Bipolar Disorder ; Circadian Rhythm ; Depression ; Humans ; Male ; Mice* ; Models, Animal* ; Motor Activity ; Photoperiod ; Physical Exertion ; Quinpirole

Mitochondrial protein Nfu1 plays an important role in the assembly of mitochondrial Fe-S clusters and intracellular iron homeostasis in the model yeast Saccharomyces cerevisiae. In this study, we identified the Nfu1 ortholog in the human fungal pathogen Cryptococcus neoformans. Our data showed that C. neoformans Nfu1 localized in the mitochondria and influenced homeostasis of essential metals such as iron, copper and manganese. Marked growth defects were observed in the mutant lacking NFU1, which suggests a critical role of Nfu1 in Fe-S cluster biosynthesis and intracellular metal homeostasis in C. neoformans.
Copper ; Cryptococcus neoformans* ; Homeostasis* ; Humans ; Iron ; Manganese ; Metals* ; Mitochondria ; Mitochondrial Proteins* ; Saccharomyces cerevisiae ; Yeasts

Objective: Data processing in analysis of circadian rhythm was performed in various ways. However, there was a lack of evidence for the optimal analysis of circadian rest-activity rhythm. Therefore, we aimed to perform mathematical simulations of data processing to investigate proper evidence for the optimal analysis of circadian rest-activity rhythm. Methods: Locomotor activities of 20 ICR male mice were measured by infrared motion detectors. The data of locomotor activities was processed using data summation, data average, and data moving average methods for cosinor analysis. Circadian indices were estimated according to time block, respectively. Also, statistical F and p-values were calculated by zero-amplitude test. Results: The data moving average result showed well-fitted cosine curves independent of data processing time. Meanwhile, the amplitude, MESOR, and acrophase were properly estimated within 800 seconds in data summation and data average methods. Conclusion These findings suggest that data moving average would be an optimal method for data processing in a cosinor analysis and data average within 800-second data processing time might be adaptable. The results of this study can be helpful to analyze circadian restactivity rhythms and integrate the results of the studies using different data processing methods.

Objective: Behavioral assessments that effectively predict sleep-wake states were tried in animal research. This study aimed to examine the prediction power of an infrared locomotion detector on the sleep-wake states in ICR (Institute Cancer Research) mice. We also explored the influence of the durations and ways of data processing on the prediction power. Methods: The locomotor activities of seven male mice in home cages were recorded by infrared detectors. Their sleep-wake states were assessed by video analysis. Using the receiver operating characteristic curve analysis, the cut-off score was determined, then the area under the curve (AUC) values of the infrared motion detector that predicted sleep-wake states were calculated. In order to improve the prediction power, the four ways of data processing on the prediction power were performed by Matlab 2013b. Results: In the initial analysis of raw data, the AUC value was 0.785, but it gradually reached to 0.942 after data summation. The simple data averaging and summation among four different methods showed the maximal AUC value. The 10-minute data summation improved sensitivity (0.889) and specificity (0.901) significantly from the baseline value (sensitivity 0.615; specificity 0.936) (p ＜ 0.001). Conclusion This study suggests that the locomotor activity measured by an infrared motion detector might be useful to predict the sleep-wake states in ICR mice. It also revealed that only simple data summation may improve the predictive power. Using daily locomotor activities measured by an infrared motion detector is expected to facilitate animal research related to sleep-wake states.