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Introduction: Hypersensitivity reactions (HSRs) to chemotherapy are serious adverse events associated with cancer drug therapy and can occur with any antitumor drug. This study investigated the safety and efficacy of carboplatin desensitization therapy in Japan and established a method for treating carboplatin HSRs. Methods: Patients diagnosed with gynecological (ovarian, endometrial, or cervical) cancers who underwent carboplatin desensitization therapy between 2016 and 2020 at the Gynecologic Cancer Study Group of Japan Clinical Oncology Group were included. The carboplatin desensitization therapy at each institution and the implementation cases were registered in an online case report form. Results: This retrospective study enrolled 136 patients (ovarian, 108; endometrial, 17; and cervical cancer, 11). Pre‐existing allergies were present in 37 (27.2%) patients, and 32 (23.5%) patients exhibited prodromal symptoms during treatment before HSR onset. Erythema was the most common symptom at HSR onset, affecting 93 (68.4%) patients, followed by itching in 72 (52.9%) patients and decreased oxygen saturation in 43 (31.6%) patients. Loss of consciousness occurred in three (2.2%) patients. The most common timing of HSR onset was during the first recurrence treatment (47%). The mean total carboplatin dose until HSR onset was 7331 (2620–18,282) mg, and the mean number of doses was 14 (4–63). Desensitization treatment was completed in 75% of cases, and breakthrough HSRs occurred in 25% (34/136). No deaths occurred in the study cohort. The risk factors for HSRs were not identified. Conclusion: Although carboplatin desensitization therapy has high success rates in Japan, erythema and pruritus are important HSRs to consider. [ABSTRACT FROM AUTHOR]

FE UPTAKE‐INDUCING PEPTIDE1 (FEP1), also named IRON MAN3 (IMA3) is a short peptide involved in the iron deficiency response in Arabidopsis thaliana. Recent studies uncovered its molecular function, but its physiological function in the systemic Fe response is not fully understood. To explore the physiological function of FEP1 in iron homoeostasis, we performed a transcriptome analysis using the FEP1 loss‐of‐function mutant fep1‐1 and a transgenic line with oestrogen‐inducible expression of FEP1. We determined that FEP1 specifically regulates several iron deficiency‐responsive genes, indicating that FEP1 participates in iron translocation rather than iron uptake in roots. The iron concentration in xylem sap under iron‐deficient conditions was lower in the fep1‐1 mutant and higher in FEP1‐induced transgenic plants compared with the wild type (WT). Perls staining revealed a greater accumulation of iron in the cortex of fep1‐1 roots than in the WT root cortex, although total iron levels in roots were comparable in the two genotypes. Moreover, the fep1‐1 mutation partially suppressed the iron overaccumulation phenotype in the leaves of the oligopeptide transporter3‐2 (opt3‐2) mutant. These data suggest that FEP1 plays a pivotal role in iron movement and in maintaining the iron quota in vascular tissues in Arabidopsis. [ABSTRACT FROM AUTHOR]

Solitary fibrous tumors (SFTs) are rare mesenchymal cell‐derived tumors that can cause substantial bleeding during surgery due to hyper‐vascularization. We report a case of a large retroperitoneal SFT resected completely using an intra‐aortic balloon. A 71‐year‐old female with a history of type 2 diabetes mellitus presented with a tumor that was diagnosed as an insulin‐like growth factor‐II‐producing benign SFT using computed tomography‐guided biopsy. The tumor had grown from 6 to 20 cm in diameter within 4 years, with concurrent and severe hypoglycemia. Preoperative computed tomography findings showed substantial blood flow toward the tumor. The retroperitoneal tumor was observed to be widely attached. Substantial hemorrhaging during tumor resection was observed despite vascular embolism. We inflated the intra‐aortic balloon for 45 min and resected the tumor completely. In conclusion, large SFT resection requires preoperative tumor blood flow evaluation and preparation of both a vascular embolism and an intra‐aortic balloon. [ABSTRACT FROM AUTHOR]

At the 73rd Annual Congress of the Japan Society of Obstetrics and Gynecology, young doctors from Japan and South Korea made presentations on the present condition of risk‐reducing surgery for hereditary breast and ovarian cancer (RRSO) in their respective country. RRSO was insured in Japan in April 2020, whereas in South Korea, it was insured 7 years earlier in 2013. In Japan, certification criteria have been set for facilities that perform RRSO, and the number of facilities is increasing, but regional disparities still exist in its distribution. The number of gBRCA1/2 testing facilities is larger, and the cost is more affordable in South Korea than in Japan. Additionally, South Korea provides genetic counseling to a wider range of relatives compared to Japan. In the future, as the indications for the gBRCA1/2 test have expanded as a companion diagnostic for the use of PARP inhibitors, it is expected that the number of candidates for the gBRCA1/2 mutation test and RRSO will increase in Japan. It is important to increase the number of BRCA tests while maintaining the quality of genetic counseling in order to provide adequate information on BRCA mutations and RRSO for patients to support their decision. For the development of hereditary breast and ovarian cancer (HBOC) medical care, it is necessary to publish a nationwide database in Japan and continue to analyze and discuss the data based on the results. [ABSTRACT FROM AUTHOR]

SUMMARY: Rhizoctonia solani is a soil‐borne necrotrophic fungus that causes sheath blight in grasses. The basal resistance of compatible interactions between R. solani and rice is known to be modulated by some WRKY transcription factors (TFs). However, genes and defense responses involved in incompatible interaction with R. solani remain unexplored, because no such interactions are known in any host plants. Recently, we demonstrated that Bd3‐1, an accession of the model grass Brachypodium distachyon, is resistant to R. solani and, upon inoculation with the fungus, undergoes rapid induction of genes responsive to the phytohormone salicylic acid (SA) that encode the WRKY TFs BdWRKY38 and BdWRKY44. Here, we show that endogenous SA and these WRKY TFs positively regulate this accession‐specific R. solani resistance. In contrast to a susceptible accession (Bd21), the infection process in the resistant accessions Bd3‐1 and Tek‐3 was suppressed at early stages before the development of fungal biomass and infection machinery. A comparative transcriptome analysis during pathogen infection revealed that putative WRKY‐dependent defense genes were induced faster in the resistant accessions than in Bd21. A gene regulatory network (GRN) analysis based on the transcriptome dataset demonstrated that BdWRKY38 was a GRN hub connected to many target genes specifically in resistant accessions, whereas BdWRKY44 was shared in the GRNs of all three accessions. Moreover, overexpression of BdWRKY38 increased R. solani resistance in Bd21. Our findings demonstrate that these resistant accessions can activate an incompatible host response to R. solani, and BdWRKY38 regulates this response by mediating SA signaling. Significance Statement: Rhizoctonia solani is a plant pathogenic fungus that causes sheath blight in grasses. In accordance with its necrotrophic lifestyle with a broad host range, the incompatible plant–R. solani interactions are not known in any host plants. Here, we demonstrate that such interactions could occur in the small grass Brachypodium distachyon, and BdWRKY38 is a key transcription factor that positively regulates this interaction by mediating the salicylic acid signaling pathway. [ABSTRACT FROM AUTHOR]

Aim: Previous reports showed associations between oxytocin induced labor and mental disorders in offspring. However, those reports are restricted in epidemiological analyses and its mechanism remains unclear. In this study, we hypothesized that induced labor directly causes brain damage in newborns and results in the development of mental disorders. Therefore we aimed to investigate this hypothesis with animal model. Methods: The animal model of induced labor was established by subcutaneous oxytocin administration to term‐pregnant C57BL/6J mice. We investigated the neonatal brain damage with evaluating immediate early gene expression (c‐Fos, c‐Jun and JunB) by quantitative polymerase reaction and TdT‐mediated dUTP nick end labeling staining. To investigate the injured brain cell types, we performed double‐immunostaining with TdT‐mediated dUTP nick end labeling staining and each brain component specific protein, such as Oligo2, NeuN, GFAP and Iba1. Results: Brain damage during induced labor led to cell death in specific brain regions, which are implicated in mental disorders, in only male offspring at P0. Furthermore, oligodendrocyte precursors were selectively vulnerable compared to the other cell types. This oligodendrocyte‐specific impairment during the perinatal period led to an increased numbers of Olig2‐positive cells at P5. Expression levels of oxytocin and Oxtr in the fetal brain were not affected by the oxytocin administered to mothers during induced labor. Conclusion: Oligodendrocyte cell death in specific brain regions, which was unrelated to the oxytocin itself, was caused by induced labor in only male offspring. This may be an underlying mechanism explaining the human epidemiological data suggesting an association between induced labor and mental disorders. [ABSTRACT FROM AUTHOR]

Uterine leiomyosarcoma (LMS) is a rare tumor. It has not been established if these tumors arise de novo or from pre‐existing leiomyomas (LM). We report a case herein of LMS arising from a subserosal LM. A 47‐year‐old nulliparous woman was diagnosed with a uterine tumor measuring 30 cm in diameter by pelvic magnetic resonance imaging. Serum CA‐125 level was 369 U/mL, and the lactate dehydrogenase level was elevated (565 IU/L, respectively). Positron emission tomography‐computed tomography revealed abnormal uptake (SUVmax = 25.29) of the abdominal tumor. Upon laparotomy, a large tumor with solid and cystic components was shown to arise from a subserosal LM, with invasion into the greater omentum and small intestine. Abdominal hysterectomy, bilateral salpingo‐oophorectomy, omentectomy and small intestine resection were performed. Macroscopic findings showed that the LMS was adherent to a subserosal LM, without continuity between the tumor and the uterus. Our case supports the hypothesis that LMS can arise from a pre‐existing LM. [ABSTRACT FROM AUTHOR]

Plants closing stomata in the presence of harmful gases is believed to be a stress avoidance mechanism. SO2, one of the major airborne pollutants, has long been reported to induce stomatal closure, yet the mechanism remains unknown. Little is known about the stomatal response to airborne pollutants besides O3. SLOW ANION CHANNEL‐ASSOCIATED 1 (SLAC1) and OPEN STOMATA 1 (OST1) were identified as genes mediating O3‐induced closure. SLAC1 and OST1 are also known to mediate stomatal closure in response to CO2, together with RESPIRATORY BURST OXIDASE HOMOLOGs (RBOHs). The overlaying roles of these genes in response to O3 and CO2 suggested that plants share their molecular regulators for airborne stimuli. Here, we investigated and compared stomatal closure event induced by a wide concentration range of SO2 in Arabidopsis through molecular genetic approaches. O3‐ and CO2‐insensitive stomata mutants did not show significant differences from the wild type in stomatal sensitivity, guard cell viability, and chlorophyll content revealing that SO2‐induced closure is not regulated by the same molecular mechanisms as for O3 and CO2. Nonapoptotic cell death is shown as the reason for SO2‐induced closure, which proposed the closure as a physicochemical process resulted from SO2 distress, instead of a biological protection mechanism. Sulfur dioxide (SO2) is a major air pollutant known to injure plants and induce stomatal closure. Here, we identified H2SO3 as the responsible SO2‐derived chemical species for the induction of stomatal closure through nonapoptotic cell death in the guard cells. Furthermore, studies utilizing O3‐ and CO2‐insensitive stomata mutants revealed that the molecular mechanism for SO2‐induced stomatal closure is distinct from O3 and CO2. [ABSTRACT FROM AUTHOR]

Induced pluripotent stem (iPS) cell technology lead terminally differentiated cells into the pluripotent stem cells through the expression of defined reprogramming factors. Although, iPS cells have been established in a number of mammalian species, including mouse, human, and monkey, studies on iPS cells in avian species are still very limited. To establish chick iPS cells, six factors were used within the poly-cistronic reprogramming vector (PB-R6F), containing M3O (MyoD derived transactivation domain fused with Oct3/4), Sox2, Klf4, c-Myc, Lin28, and Nanog. The PB-R6F derived iPS cells were alkaline-phosphatase and SSEA-1 positive, which are markers of pluripotency. Elevated levels of endogenous Oct3/4 and Nanog genes were detected in the established iPS cells, suggesting the activation of the FGF signaling pathway is critical for the pluripotent status. Histological analysis of teratoma revealed that the established chick iPS cells have differentiation ability into three-germ-layer derived tissues. This is the first report of establishment of avian derived iPS cells with a single poly-cistronic transposon based expression system. The establishment of avian derived iPS cells could contribute to the genetic conservation and modification of avian species. [ABSTRACT FROM AUTHOR]

* Rhizoctonia solani is a soil-borne fungus causing sheath blight. In consistent with its necrotrophic life style, no rice cultivars fully resistant to R. solani are known, and agrochemical plant defense activators used for rice blast, which upregulate a phytohormonal salicylic acid (SA)-dependent pathway, are ineffective towards this pathogen. As a result of the unavailability of genetics, the infection process of R. solani remains unclear. * We used the model monocotyledonous plants Brachypodium distachyon and rice, and evaluated the effects of phytohormone-induced resistance to R. solani by pharmacological, genetic and microscopic approaches to understand fungal pathogenicity. * Pretreatment with SA, but not with plant defense activators used in agriculture, can unexpectedly induce sheath blight resistance in plants. SA treatment inhibits the advancement of R. solani to the point in the infection process in which fungal biomass shows remarkable expansion and specific infection machinery is developed. The involvement of SA in R. solani resistance is demonstrated by SA-deficient NahG transgenic rice and the sheath blight-resistant B. distachyon accessions, Bd3-1 and Gaz-4, which activate SA-dependent signaling on inoculation. * Our findings suggest a hemi-biotrophic nature of R. solani, which can be targeted by SA-dependent plant immunity. Furthermore, B. distachyon provides a genetic resource that can confer disease resistance against R. solani to plants. [ABSTRACT FROM AUTHOR]

Meiotic recombination is initiated by DNA double-stranded breaks introduced by the SPO11 protein. Despite a decade of research, the biochemical functions of SPO11 remain largely unknown, perhaps because of difficulties in studying the functionally active SPO11. Arabidopsis thaliana encodes three SPO11-related proteins, two of which (SPO11-1 and SPO11-2) are required for, and cooperate in, meiosis. We isolated soluble SPO11-1, fused with or free of a trigger factor-tag at its N terminus. The tag-free SPO11-1 needed to interact physically with soluble SPO11-1 to maintain its solubility, suggesting a multimeric active form including a solubilizing protein cofactor. An N-terminal fragment of PRD1, a SPO11-1-interacting protein required for normal meiosis, but not SPO11-2, forms a soluble complex with trigger factor-tagged SPO11-1, but the trigger factor-tag was required for the solubility. Formation of the complex is not sufficient to express endonuclease activity. Trigger factor-tagged SPO11-1 exhibited DNA-binding activities: Glu substitutions of the invariant Gly215 and Arg222 and of the nonconserved Arg223 and Arg226 in a conserved motif (G215E, R222E, R223E, R226E) reduced the DNA-binding ability in vitro, but substitutions of the conserved Arg130 and invariant Tyr103 (a residue in the putative endonuclease-active center) and of Arg residues outside conserved motifs by Glu or Phe (R130E, Y103F, R207E and R254E), did not. Tests for the ability of mutant spo11-1 proteins to complement the silique-defective phenotype of a spo11-1-homozygous mutant in vivo revealed that R222E and G215E induced serious deficiencies, while R130E caused a partial defect in silique formation. Thus, the Gly215, Arg222 and Arg223 residues of SPO11-1 form a DNA-binding surface that is functional in meiosis. [ABSTRACT FROM AUTHOR]

Understanding abiotic stress responses in plants is an important and challenging topic in plant research. Physiological and molecular biological analyses have allowed us to draw a picture of abiotic stress responses in various plants, and determination of the Arabidopsis genome sequence has had a great impact on this research field. The availability of the complete genome sequence has facilitated access to essential information for all genes, e.g. gene products and their function, transcript levels, putative cis-regulatory elements, and alternative splicing patterns. These data have been obtained from comprehensive transcriptome analyses and studies using full-length cDNA collections and T-DNA- or transposon-tagged mutant lines, which were also enhanced by genome sequence information. Moreover, studies on novel regulatory mechanisms involving use of small RNA molecules, chromatin modulation and genomic DNA modification have enabled us to recognize that plants have evolved complicated and sophisticated systems in response to complex abiotic stresses. Integrated data obtained with various ‘omics’ approaches have provided a more comprehensive picture of abiotic stress responses. In addition, research on stress responses in various plant species other than Arabidopsis has increased our knowledge regarding the mechanisms of plant stress tolerance in nature. Based on this progress, improvements in crop stress tolerance have been attempted by means of gene transfer and marker-assisted breeding. In this review, we summarize recent progress in abiotic stress studies, especially in the post-genomic era, and offer new perspectives on research directions for the next decade. [ABSTRACT FROM AUTHOR]

The phytohormone abscisic acid (ABA) regulates physiologically important stress and developmental responses in plants. To reveal the mechanism of response to ABA, we isolated several novel ABA-hypersensitive Arabidopsis thaliana mutants, named ahg ( BA- ypersensitive ermination). ahg1-1 mutants showed hypersensitivity to ABA, NaCl, KCl, mannitol, glucose and sucrose during germination and post-germination growth, but did not display any significant phenotypes in adult plants. ahg1-1 seeds accumulated slightly more ABA before stratification and showed increased seed dormancy. Map-based cloning of AHG1 revealed that ahg1-1 has a nonsense mutation in a gene encoding a novel protein phosphatase 2C (PP2C). We previously showed that the ahg3-1 mutant has a point mutation in the AtPP2CA gene, which encodes another PP2C that has a major role in the ABA response in seeds ( Yoshida et al., 2006b ). The levels of AHG1 mRNA were higher in dry seeds and increased during late seed maturation – an expression pattern similar to that of ABI5. Transcriptome analysis revealed that, in ABA-treated germinating seeds, many seed-specific genes and ABA-inducible genes were highly expressed in ahg1-1 and ahg3-1 mutants compared with the wild-type. Detailed analysis suggested differences between the functions of AHG1 and AHG3. Dozens of genes were expressed more strongly in the ahg1-1 mutant than in ahg3-1. Promoter–GUS analyses demonstrated both overlapping and distinct expression patterns in seed. In addition, the ahg1-1 ahg3-1 double mutant was more hypersensitive than either monogenic mutant. These results suggest that AHG1 has specific functions in seed development and germination, shared partly with AHG3. [ABSTRACT FROM AUTHOR]

Mutant lines covering all Arabidopsis genes allow us to pursue systematic functional genomics. A comprehensive phenotype description, called a phenome, is highly sought after in the profiling of -omics data. We selected 4000 transposon-insertional lines with transposon insertions in their gene-coding regions, and systematically observed the visible phenotype of each line. For the first 3 weeks after germination, plants were grown on agar plates and the juvenile phenotypes were recorded. Then the plants were transferred to soil and their phenotypes were recorded at each growth stage. About 140 lines showed clear and reproducible visible phenotypes, including novel phenotypic mutants as well as previously reported ones. All descriptions of the mutants showing visible phenotypes were classified into eight primary categories (seedling, leaves, flowering and growth, stems, branching, flowers, siliques and seed yield) and 43 secondary categories of morphological phenotypes. Phenotypic images have been entered into a searchable database ( ). One example investigated through the use of plural alleles was a mutant of a novel gene related to glycerolipid biosynthesis, with a unique visible phenotype of sepal opening. Our results suggest that we can find more novel visible phenotypes and their corresponding genes, and that phenotypic mutants of gene knockouts are not exhausted yet. This study provides basic data on large-scale phenotyping of gene knockout lines in plants, and will contribute to the completion of an international effort to develop a phenome database of all the functional genes in Arabidopsis. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that mRNA degradation systems are crucial for various biological processes in eukaryotes. Here we provide evidence that an mRNA degradation system is associated with some plant hormones and stress responses in plants. We analysed a novel Arabidopsis abscisic acid (ABA)-hypersensitive mutant, ahg2-1, that showed ABA hypersensitivity not only in germination, but also at later developmental stages, and that displayed pleiotropic phenotypes. We found that ahg2-1 accumulated more endogenous ABA in seeds and mannitol-treated plants than did the wild type. Microarray experiments showed that the expressions of ABA-, salicylic acid- and stress-inducible genes were increased in normally grown ahg2-1 plants, suggesting that the ahg2-1 mutation somehow affects various stress responses as well as ABA responses. Map-based cloning of AHG2 revealed that this gene encodes a poly(A)-specific ribonuclease (AtPARN) that is presumed to function in mRNA degradation. Detailed analysis of the ahg2-1 mutation suggests that the mutation reduces AtPARN production. Interestingly, expression of AtPARN was induced by treatment with ABA, high salinity and osmotic stress. These results suggest that both upregulation and downregulation of gene expression by the mRNA-destabilizing activity of AtPARN are crucial for proper ABA, salicylic acid and stress responses. [ABSTRACT FROM AUTHOR]

More than 10 000 transposon-tagged lines were constructed by using the Activator ( Ac)/ Dissociation ( Ds) system in order to collect insertional mutants as a useful resource for functional genomics of Arabidopsis. The flanking sequences of the Ds element in the 11 800 independent lines were determined by high-throughput analysis using a semi-automated method. The sequence data allowed us to map the unique insertion site on the Arabidopsis genome in each line. The Ds element of 7566 lines is inserted in or close to coding regions, potentially affecting the function of 5031 of 25 000 Arabidopsis genes. Half of the lines have Ds insertions on chromosome 1 (Chr. 1), in which donor lines have a donor site. In the other half, the Ds insertions are distributed throughout the other four chromosomes. The intrachromosomal distribution of Ds insertions varies with the donor lines. We found that there are hot spots for Ds transposition near the ends of every chromosome, and we found some statistical preference for Ds insertion targets at the nucleotide level. On the basis of systematic analysis of the Ds insertion sites in the 11 800 lines, we propose the use of Ds-tagged lines with a single insertion in annotated genes for systematic analysis of phenotypes (phenome analysis) in functional genomics. We have opened a searchable database of the insertion-site sequences and mutated genes ( ) and are depositing these lines in the RIKEN BioResource Center as available resources ( ). [ABSTRACT FROM AUTHOR]

Among all AND-EXOR expression that represent a logic function f, those with a minimum number of products are called minimum AND-EXOR expressions of f. The number of products in the minimum AND-EXOR expressions of f is denoted by τ(f). The minimization algorithms of AND-EXOR expressions take a great deal of time for computing (time complexity O(22n)), where n is the number of variables. Thus it is necessary to develop a simplification algorithm that does not always find the exact minimum AND-EXOR expressions but runs fast. This paper presents a simplification algorithm of AND-EXOR expressions, which partially guarantees minimality and has the following properties: (1) it computes a minimum AND-EXOR expression for a logic function f with τ(f) < 3(k + 1), where k is a nonnegative integer; (2) if an AND-EXOR expression obtained by this algorithm takes less than or equal to 3(k + 1) of products, then it is minimum; and (3) its time complexity is O(√3ken2+(k+C)n). From the experimental results for k = 0, 1, 2, we can conclude that its computational time is practical for n = 20, 7, 6, respectively. Modifying this algorithm, we present an exact minimization algorithm for 5-variable functions, which is faster than previously known ones. [ABSTRACT FROM AUTHOR]