A Comprehensive Landscape of De Novo Malignancy After Double Lung Transplantation.

Although the association between post-transplant malignancy (PTM) and immunosuppressive therapy after organ transplantation has been studied, an integrated review of PTM after lung transplantation is lacking. We investigated the incidence and types of de novo PTM and its impact on survival following double lung transplantation (DLT). The incidence and type of PTM as well as the annual and cumulative risks of each malignancy after DLT were analyzed. The overall survival (OS) of recipients with or without PTM was compared by the Kaplan-Meier survival method and landmark analysis. There were 5,629 cases (23.52%) with 27 types of PTMs and incidences and OS varied according to the types of PTMs. The recipients with PTM showed a significantly longer OS than those without PTM (p < 0.001). However, while the recipients with PTM showed significantly better OS at 3, and 5 years (p < 0.001, p = 0.007), it was worse at the 10-year landmark time (p = 0.013). And the single PTM group showed a worse OS rate than the multiple PTM group (p < 0.001). This comprehensive report on PTM following DLT can help understand the risks and timing of PTM to improve the implementation of screening and treatment.

Sequencing and de novo assembly of the Koshihikari genome and identification of the genomic region related to the eating quality of cooked rice.

The japonica rice (Oryza sativa L.) cultivar Koshihikari is considered an important breeding material with good eating quality (EQ). To effectively utilize Koshihikari in molecular breeding programs, determining its whole genome sequence including cultivar-specific segment is crucial. Here, the Koshihikari genome was sequenced using Nanopore and Illumina platforms, and de novo assembly was performed. A highly contiguous Koshihikari genome sequence was compared with Nipponbare, the reference genome of japonica. Genome-wide synteny was observed, as expected, without large structural variations. However, several gaps in alignment were detected on chromosomes 3, 4, 9, and 11. It was notable that previously identified EQ-related QTLs were found in these gaps. Moreover, sequence variations were identified in chromosome 11 at a region flanking the P5 marker, one of the significant markers of good EQ. The Koshihikari-specific P5 region was found to be transmitted through the lineage. High EQ cultivars derived from Koshihikari possessed P5 sequences; on the other hand, Koshihikari-derived low EQ cultivars didn't contain the P5 region, which implies that the P5 genomic region affects the EQ of Koshihikari progenies. The EQ of near-isogenic lines (NILs) of Samnam (a low EQ cultivar) genetic background harboring the P5 segment was improved compared to that of Samnam in Toyo taste value. The structure of the Koshihikari-specific P5 genomic region associated with good EQ was analyzed, which is expected to facilitate the molecular breeding of rice cultivars with superior EQ. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01335-3.

OsCOP1 regulates embryo development and flavonoid biosynthesis in rice (Oryza sativa L.).

KEY MESSAGE: Novel mutations of OsCOP1 were identified to be responsible for yellowish pericarp and embryo lethal phenotype, which revealed that OsCOP1 plays a crucial role in flavonoid biosynthesis and embryogenesis in rice seed. Successful production of viable seeds is a major component of plant life cycles, and seed development is a complex, highly regulated process that affects characteristics such as seed viability and color. In this study, three yellowish-pericarp embryo lethal (yel) mutants, yel-hc, yel-sk, and yel-cc, were produced from three different japonica cultivars of rice (Oryza sativa L). Mutant seeds had yellowish pericarps and exhibited embryonic lethality, with significantly reduced grain size and weight. Morphological aberrations were apparent by 5 days after pollination, with abnormal embryo development and increased flavonoid accumulation observed in the yel mutants. Genetic analysis and mapping revealed that the phenotype of the three yel mutants was controlled by a single recessive gene, LOC_Os02g53140, an ortholog of Arabidopsis thaliana CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1). The yel-hc, yel-sk, and yel-cc mutants carried mutations in the RING finger, coiled-coil, and WD40 repeat domains, respectively, of OsCOP1. CRISPR/Cas9-targeted mutagenesis was used to knock out OsCOP1 by targeting its functional domains, and transgenic seed displayed the yel mutant phenotype. Overexpression of OsCOP1 in a homozygous yel-hc mutant background restored pericarp color, and the aberrant flavonoid accumulation observed in yel-hc mutant was significantly reduced in the embryo and endosperm. These results demonstrate that OsCOP1 is associated with embryo development and flavonoid biosynthesis in rice grains. This study will facilitate a better understanding of the functional roles of OsCOP1 involved in early embryogenesis and flavonoid biosynthesis in rice seeds.

Identification of a novel SPLIT-HULL (SPH) gene associated with hull splitting in rice (Oryza sativa L.).

KEY MESSAGE: The split-hull phenotype caused by reduced lemma width and low lignin content is under control of SPH encoding a type-2 13-lipoxygenase and contributes to high dehulling efficiency. Rice hulls consist of two bract-like structures, the lemma and palea. The hull is an important organ that helps to protect seeds from environmental stress, determines seed shape, and ensures grain filling. Achieving optimal hull size and morphology is beneficial for seed development. We characterized the split-hull (sph) mutant in rice, which exhibits hull splitting in the interlocking part between lemma and palea and/or the folded part of the lemma during the grain filling stage. Morphological and chemical analysis revealed that reduction in the width of the lemma and lignin content of the hull in the sph mutant might be the cause of hull splitting. Genetic analysis indicated that the mutant phenotype was controlled by a single recessive gene, sph (Os04g0447100), which encodes a type-2 13-lipoxygenase. SPH knockout and knockdown transgenic plants displayed the same split-hull phenotype as in the mutant. The sph mutant showed significantly higher linoleic and linolenic acid (substrates of lipoxygenase) contents in spikelets compared to the wild type. It is probably due to the genetic defect of SPH and subsequent decrease in lipoxygenase activity. In dehulling experiment, the sph mutant showed high dehulling efficiency even by a weak tearing force in a dehulling machine. Collectively, the results provide a basis for understanding of the functional role of lipoxygenase in structure and maintenance of hulls, and would facilitate breeding of easy-dehulling rice.

Association between sequence variants in panicle development genes and the number of spikelets per panicle in rice.

BACKGROUND: Balancing panicle-related traits such as panicle length and the numbers of primary and secondary branches per panicle, is key to improving the number of spikelets per panicle in rice. Identifying genetic information contributes to a broader understanding of the roles of gene and provides candidate alleles for use as DNA markers. Discovering relations between panicle-related traits and sequence variants allows opportunity for molecular application in rice breeding to improve the number of spikelets per panicle. RESULTS: In total, 142 polymorphic sites, which constructed 58 haplotypes, were detected in coding regions of ten panicle development gene and 35 sequence variants in six genes were significantly associated with panicle-related traits. Rice cultivars were clustered according to their sequence variant profiles. One of the four resultant clusters, which contained only indica and tong-il varieties, exhibited the largest average number of favorable alleles and highest average number of spikelets per panicle, suggesting that the favorable allele combination found in this cluster was beneficial in increasing the number of spikelets per panicle. CONCLUSIONS: Favorable alleles identified in this study can be used to develop functional markers for rice breeding programs. Furthermore, stacking several favorable alleles has the potential to substantially improve the number of spikelets per panicle in rice.

Effects of cannabinoids in Parkinson's disease animal models: a systematic review and meta-analysis.

Objectives: Cannabis has been proposed as a potential treatment for Parkinson's disease (PD) due to its neuroprotective benefits. However, there has been no rigorous review of preclinical studies to evaluate any potential treatment effect. This systematic review was undertaken to provide evidence in support or against a treatment effect of cannabinoids in animal models of PD. Methods: Databases were searched for any controlled comparative studies that assessed the effects of any cannabinoid, cannabinoid-based treatment or endocannabinoid transport blocker on behavioural symptoms in PD animal models. Results: A total of 41 studies were identified to have met the criteria for this review. 14 of these studies were included in meta-analyses of rotarod, pole and open field tests. Meta-analysis of rotarod tests showed a weighted mean difference of 31.63 s for cannabinoid-treated group compared with control. Meta-analysis of pole tests also showed a positive treatment effect, evidenced by a weighted mean difference of -1.51 s for cannabinoid treat group compared with control. However, meta-analysis of open field test demonstrated a standardised mean difference of only 0.36 indicating no benefit. Conclusion: This review demonstrates cannabinoid treatment effects in alleviating motor symptoms of PD animal models and supports the conduct of clinical trials of cannabis in PD population. However, there is no guarantee of successful clinical translation of this outcome because of the many variables that might have affected the results, such as the prevalent unclear and high risk of bias, the different study methods, PD animal models and cannabinoids used.

Identification and characterization of the stunted sterile (ss) mutant in rice.

BACKGROUND: Proper organ development is pivotal for normal rice growth and production. Many genes are involved in this process, and these genes provide a basis for rice breeding. OBJECTIVE: To identify a novel mutation causing developmental defects in rice. METHODS: The phenotype of a rice mutant, stunted sterile (ss), identified from the japonica rice cultivar Samkwang treated with N-methyl-N-nitrosourea, was characterized, including anatomical and pollen activity analyses. A genetic analysis and fine mapping were performed to identify a candidate locus, followed by a sequence analysis to determine the causal mutation for the phenotype. RESULTS: Compared with wild-type plants, the mutant exhibited a 34% reduction in height, 46% reduction in flag leaf width, and complete panicle sterility. Cell proliferation in the leaf and pollen viability were significantly inhibited in the mutant. The mutant phenotypes were controlled by a single recessive gene that was fine-mapped to an 84 kb region between two SNP markers on the short arm of chromosome 5. A candidate gene analysis determined that the mutant carries an 11 bp insertion in the coding region of LOC_Os05g03550, which encodes a protein containing two SANT domains, resulting in a premature termination codon before the conserved domain. CONCLUSIONS: We identified a novel rice gene, Stunted sterile, involved in the regulation of various developmental processes. Our findings improve our understanding of the role of chromatin remodeling in organ development and have implications for breeding owing to the broad effects of the gene on plant growth.

Identification and Characterization of LARGE EMBRYO, a New Gene Controlling Embryo Size in Rice (Oryza sativa L.).

BACKGROUND: Although embryo accounts for only 2-3% of the total weight of a rice grain, it is a good source of various nutrients for human health. Because enlarged embryo size causes increase of the amount of nutrients and bioactive compounds stored within rice grain, giant embryo mutants of rice (Oryza sativa L.) are excellent genetic resources for improving the nutritional value of rice grains. RESULTS: Three giant embryo mutants, including large embryo (le), giant embryo (ge) and super-giant embryo (ges), with variable embryo size were used in this study. We investigated whether genes controlling embryo size in these mutants (le, ge and ges) were allelic to each other. Although ge and ges was allelic to GIANT EMBRY (GE), le was not allelic to ge and ges in allelism test. The GE gene carried a unique nucleotide substitution in each of the two mutants (ge and ges), resulting in non-synonymous mutations in exon 2 of GE in both mutants. However, the GE gene of the le mutant did not carry any mutation, suggesting that the enlarged embryo phenotype of le was governed by another gene. Using map-based cloning, we mapped the LE gene to the short arm of chromosome 3. The le mutant showed mild enlargement in embryo size, which resulted from an increase in the size of scutellar parenchyma cells. The LE encodes a C3HC4-type RING finger protein and was expressed to relatively high levels in seeds at a late developmental stage. Knockdown of LE expression using RNA interference increased the embryo size of rice grains, confirming the role of LE in determining the embryo size. CONCLUSION: Overall, we identified a new gene controlling embryo size in rice. Phenotypic and molecular characterization results suggest that the le mutant will serve as a valuable resource for developing new rice cultivars with large embryos and nutrient-dense grains.

Identification of a Spotted Leaf Sheath Gene Involved in Early Senescence and Defense Response in Rice.

Lesion mimic mutants (LMMs) commonly exhibit spontaneous cell death similar to the hypersensitive defense response that occurs in plants in response to pathogen infection. Several lesion mimic mutants have been isolated and characterized, but their molecular mechanisms remain largely unknown. Here, a spotted leaf sheath (sles) mutant derived from japonica cultivar Koshihikari is described. The sles phenotype differed from that of other LMMs in that lesion mimic spots were observed on the leaf sheath rather than on leaves. The sles mutant displayed early senescence, as shown, by color loss in the mesophyll cells, a decrease in chlorophyll content, and upregulation of chlorophyll degradation-related and senescence-associated genes. ROS content was also elevated, corresponding to increased expression of genes encoding ROS-generating enzymes. Pathogenesis-related genes were also activated and showed improved resistance to pathogen infection on the leaf sheath. Genetic analysis revealed that the mutant phenotype was controlled by a single recessive nuclear gene. Genetic mapping and sequence analysis showed that a single nucleotide substitution in the sixth exon of LOC_Os07g25680 was responsible for the sles mutant phenotype and this was confirmed by T-DNA insertion line. Taken together, our results revealed that SLES was associated with the formation of lesion mimic spots on the leaf sheath resulting early senescence and defense responses. Further examination of SLES will facilitate a better understanding of the molecular mechanisms involved in ROS homeostasis and may also provide opportunities to improve pathogen resistance in rice.

Sugary Endosperm is Modulated by Starch Branching Enzyme IIa in Rice (Oryza sativa L.).

BACKGROUND: Starch biosynthesis is one of the most important pathways that determine both grain quality and yield in rice (Oryza sativa L.). Sugary endosperm, sugary-1 (sug-1), is a mutant trait for starch biosynthesis. Rice plants carrying sug-1 produce grains that accumulate water-soluble carbohydrates instead of starch, even after maturity. Although this trait enhances the diversity of grain quality, sugary endosperm rice has hardly been commercialized due to the severely wrinkled grains and subsequent problems in milling. This study was conducted to identify the genes responsible for the sug-h phenotype through a map-based cloning technology. RESULTS: We induced a mild sugary mutant, sugary-h (sug-h) through the chemical mutagenesis on the Korean japonica cultivar Hwacheong. Grains of the sug-h mutant were translucent and amber-colored, and the endosperm appeared less wrinkled than sug-1, whereas the soluble sugar content was fairly high. These characteristics confer greater marketability to the sug-h mutant. Genetic analyses indicated that the sug-h mutant phenotype was controlled by a complementary interaction of two recessive genes, Isoamylase1 (OsISA1), which was reported previously, and Starch branching enzyme IIa (OsBEIIa), which was newly identified in this study. Complementation tests indicated that OsBEIIa regulated the properties of sugary endosperm. CONCLUSIONS: Complementary interactions between the starch biosynthesis genes OsISA1 and OsBEIIa determine the mild sugary endosperm mutant, sugary-h, in rice. Our finding may facilitate the breeding of sugaryendosperm rice for commercial benefit.

[Development of an evaluation instrument for subjects related to death].

PURPOSE: The purpose of this study was to develop an evaluation instrument integrated and interdisciplinary death education for the human service areas such as nursing, social welfare, and education and to test the reliability and validity of it. METHOD: The subjects used to verify the instrument's reliability and validity were 407 students who were enrolled in the departments of nursing, social welfare, and education in universities located in Seoul, Pusan, Daegu, and Daejeon. The data was collected from April to May, 2005, and was analyzed by SPSS/WIN 12. RESULT: A factor analysis was conducted. Items with over a .40 factor loading and over a 1.0 eigen value were selected. Nine identified factors were learning about death, role of professionals, personal attitudes, hospice care, ethics and legal issues, death and dying, spiritual aspect of death, transcultural aspect of death, and multidisciplinary theory of death. The instrument consisted of 44 items and the reliability was a cronbach's of .953. CONCLUSION: Based on the study results, the content scale developed in this study was identified as a tool with a high degree of reliability and validity.