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Growth and developmental processes are occasionally accompanied by multiple rounds of DNA replication, known as endoreduplication. Coordination between endoreduplication and cell size regulation often plays a crucial role in proper organogenesis and cell differentiation. Here, we report that the level of correlation between ploidy and cell volume is different in the outer and inner cell layers of leaves of Arabidopsis thaliana using a novel imaging technique. Although there is a well-known, strong correlation between ploidy and cell volume in pavement cells of the epidermis, this correlation was extremely weak in palisade mesophyll cells. Induction of epidermis cell identity based on the expression of the homeobox gene ATML1 in mesophyll cells enhanced the level of correlation between ploidy and cell volume to near that of wild-type epidermal cells. We therefore propose that the correlation between ploidy and cell volume is regulated by cell identity. [ABSTRACT FROM AUTHOR]

Background: Fentanyl is often used instead of morphine for the treatment of pain because it has fewer side effects. The metabolism of morphine by glucuronidation is known to be influenced by polymorphisms of the UGT2B7 gene. Some metabolic products of fentanyl are reportedly metabolized by glucuronate conjugation. The genes that are involved in the metabolic pathway of fentanyl may also influence fentanyl sensitivity. We analyzed associations between fentanyl sensitivity and polymorphisms of the UGT2B7 gene to clarify the hereditary determinants of individual differences in fentanyl sensitivity. Results: This study examined whether single-nucleotide polymorphisms (SNPs) of the UGT2B7 gene affect cold pain sensitivity and the analgesic effects of fentanyl, evaluated by a standardized pain test and fentanyl requirements in healthy Japanese subjects who underwent uniform surgical procedures. The rs7439366 SNP of UGT2B7 is reportedly associated with the metabolism and analgesic effects of morphine.We found that this SNP is also associated with the analgesic effects of fentanyl in the cold pressor-induced pain test. It suggested that the C allele of the rs7439366 SNP may enhance analgesic efficacy. Two SNPs of UGT2B7, rs4587017 and rs1002849, were also found to be novel SNPs that may influence the analgesic effects of fentanyl in the cold pressor-induced pain test. Conclusions: Fentanyl sensitivity for cold pressor-induced pain was associated with the rs7439366, rs4587017, and rs1002849 SNPs of the UGT2B7 gene. Our findings may provide valuable information for achieving satisfactory pain control and open to new avenues for personalized pain treatment. [ABSTRACT FROM AUTHOR]

Background: Many genetic and environmental factors are involved in the etiology of nicotine dependence. Although several candidate gene variations have been reported by candidate gene studies or genome-wide association studies (GWASs) to be associated with smoking behavior and the vulnerability to nicotine dependence, such studies have been mostly conducted with subjects with European ancestry. However, genetic factors have rarely been investigated for the Japanese population as GWASs. To elucidate genetic factors involved in nicotine dependence in Japanese, the present study comprehensively explored genetic contributors to nicotine dependence by using whole-genome genotyping arrays with more than 200,000 markers in Japanese subjects. Results: The subjects for the GWAS and replication study were 148 and 374 patients, respectively. A two-stage GWAS was conducted using the Fagerström Test for Nicotine Dependence (FTND), Tobacco Dependence Screener (TDS), and number of cigarettes smoked per day (CPD) as indices of nicotine dependence. For the additional association analyses, patients who underwent major abdominal surgery, patients with methamphetamine dependence/psychosis, and healthy subjects with schizotypal personality trait data were recruited. Autopsy specimens with various diseases were also evaluated. After the study of associations between more than 200,000 marker single-nucleotide polymorphisms (SNPs) and the FTND, TDS, and CPD, the nonsynonymous rs2653349 SNP (located on the gene that encodes orexin [hypocretin] receptor 2) was selected as the most notable SNP associated with FTND, with a p value of 0.0005921 in the two-stage GWAS. This possible association was replicated for the remaining 374 samples. This SNP was also associated with postoperative pain, the initiation of methamphetamine use, schizotypal personality traits, and susceptibility to goiter. Conclusions: Although the p value did not reach a conventional genome-wide level of significance in our two-stage GWAS, we obtained significant results in the subsequent analyses that suggest that the rs2653349 SNP (Val308Ile) could be a genetic factor that is related to nicotine dependence and possibly pain, schizotypal personality traits, and goiter in the Japanese population. [ABSTRACT FROM AUTHOR]

Background: The genetic etiology of schizophrenia (SCZ) overlaps with that of other major psychiatric disorders in samples of European ancestry. On the other hand, these major psychiatric disorders are distinct diagnoses that have disorder-specific genetic factors. Recently, the bipolar disorder (BIP) and SCZ Working Group of the PGC identified two genome-wide significant loci differentiating the two disorders in individuals of European descent. We hypothesized that genetic variants differentiating SCZ from BIP in Europeans as well as genetic variants related to psychiatric disorders in Europeans would overlap with genetic risk variants in Japanese SCZ patients and unaffected first-degree relatives (FRs), i.e., individuals at high risk of developing SCZ. The present study investigated transethnic polygenetic features shared between Japanese SCZ or their unaffected FRs and European patients with major psychiatric disorders by conducting polygenic risk score (PRS) analyses. Methods: To calculate PRSs for five psychiatric disorders [SCZ, BIP, major depressive disorder (MDD), autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD)] and PRSs differentiating SCZ from BIP, we utilized large-scale European genome-wide association study (GWAS) datasets as discovery samples. PRSs derived from these GWASs were calculated for 335 Japanese target subjects [131 SCZ patients, 57 of their unaffected FRs and 147 healthy controls (HCs)]. We took these PRSs based on GWASs of European psychiatric disorders (SCZ, BIP, SCZ vs BIP, MDD, ASD and ADHD) and investigated their effect on risk in Japanese SCZ patients [(i) SCZ vs FRs vs HCs, (ii) SCZ vs HCs and (iii) SCZ vs FRs] or unaffected FRs [(iv) FRs vs HCs] by PRS analyses. Results: The PRSs obtained from European SCZ samples were significantly higher in Japanese patients with SCZ than in HCs [(i) SCZ vs FRs vs HCs, a maximum at PT≤1.0: adjusted R2=0.028, p=1.30×10–3; (ii) SCZ vs HCs, a maximum at PT≤1.0: Nagelkerke’s R2=0.049, p=1.66×10– 3]. In addition, the PRSs related to European BIP were nominally higher in Japanese patients with SCZ than in HCs [(i) SCZ vs FRs vs HCs, a maximum at PT≤0.5: adjusted R2=0.016, p=0.012; (ii) SCZ vs HCs, a maximum at PT≤0.5: Nagelkerke’s R2=0.029, p=0.015]. Furthermore, PRSs differentiating SCZ patients from European BIP patients were marginally higher in Japanese SCZ patients than in HCs [(i) SCZ vs FRs vs HCs, a maximum at PT≤0.05: adjusted R2=0.010, p=0.043; (ii) SCZ vs HCs, a maximum at PT≤0.05: Nagelkerke’s R2=0.020, p=0.046]. Interestingly, the PRSs obtained from European ASD were marginally lower in Japanese FRs compared with HCs [(iv) FRs vs HCs, a maximum at PT≤0.01: Nagelkerke’s R2=0.045, p=0.013] and patients with SCZ [(iii) SCZ vs FRs, a maximum at PT≤0.2: Nagelkerke’s R2=0.023, p=0.084]. As childhood-onset patients with SCZ have showed higher PRSs for both SCZ and ASD than their unaffected siblings, we further investigated the correlation between age at onset and PRSs for both SCZ and ASD in our SCZ samples. Lower age at onset of SCZ was significantly associated with higher PRSs for ASD (PT≤0.05: beta=-0.20, p=7.13×10–3) but not PRSs for SCZ (p>0.05). Discussion: These findings suggest that polygenic factors related to European SCZ and BIP and the polygenic components differentiating SCZ from BIP can transethnically contribute to SCZ risk in Japanese people. Furthermore, we suggest that reduced levels of an ASD-related genetic factor in unaffected FRs may help protect against SCZ development. [ABSTRACT FROM AUTHOR]