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Studies focused solely on single organisms can fail to identify the networks underlying host–pathogen gene-for-gene interactions. Here, we integrate genetic analyses of rice (Oryza sativa, host) and rice blast fungus (Magnaporthe oryzae, pathogen) and uncover a new pathogen recognition specificity of the rice nucleotide-binding domain and leucine-rich repeat protein (NLR) immune receptor Pik, which mediates resistance to M. oryzae expressing the avirulence effector gene AVR-Pik. Rice Piks-1, encoded by an allele of Pik-1, recognizes a previously unidentified effector encoded by the M. oryzae avirulence gene AVR-Mgk1, which is found on a mini-chromosome. AVR-Mgk1 has no sequence similarity to known AVR-Pik effectors and is prone to deletion from the mini-chromosome mediated by repeated Inago2 retrotransposon sequences. AVR-Mgk1 is detected by Piks-1 and by other Pik-1 alleles known to recognize AVR-Pik effectors; recognition is mediated by AVR-Mgk1 binding to the integrated heavy metal-associated (HMA) domain of Piks-1 and other Pik-1 alleles. Our findings highlight how complex gene-for-gene interaction networks can be disentangled by applying forward genetics approaches simultaneously to the host and pathogen. We demonstrate dynamic coevolution between an NLR integrated domain and multiple families of effector proteins., ゲノム解読による植物病害抵抗性の解明 --イネ-いもち病菌「遺伝子対遺伝子」の戦い. 京都大学プレスリリース. 2023-02-01.

Recently, the less Shattering1 gene (SvLes1), an MYB transcription factor on chromosome V, in Setaria viridis, was reported to control the degree of seed shattering within S. viridis. SvLes1-1 and SvLes1-2 are the wild type (high shattering) allele and the reduced shattering allele, respectively. In addition to these two alleles, the loss-of-function allele through a transposable-element (TE) insertion in exon 2 was found in foxtail millet, a domesticated type of S. viridis, and was designated as SiLes1-TE. This gene is considered to be a domestication gene in foxtail millet. We screened 131 accessions of foxtail millet and found that 16 landraces (12.2%) of foxtail millet do not have the TE, despite expression of the non-shattering phenotype. We sequenced the SvLes1 gene of these 16 accessions and classified them into three alleles, SvLes1-1, SvLes1-2, and a new allele, SvLes1-3. The geographical distribution of these three alleles was different, suggesting that foxtail millet domestication and differentiation are more complex than expected.

In CheckMate 141, nivolumab significantly improved overall survival (OS) in patients with platinum-refractory recurrent or metastatic squamous cell carcinomas (R/M SCC) of the head and neck. However, reports on nivolumab for patients with non-SCC and/or a primary subsite excluded from CheckMate 141 are limited.We conducted a retrospective analysis of R/M head and neck cancer patients who received nivolumab. The study subject excluded patients with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx.A total of 59 patients were included, consisting of 40 males and 19 females with a median age of 61 years. Half of the patients had non-SCC histology. The main primary site included the sinonasal cavity (n = 18), salivary gland (n = 15), and nasopharynx (n = 13). Three (6.0%) patients achieved a complete response and 5 (10.0%) a partial response, giving an overall response rate (ORR) of 16.6%. Median time-to-treatment failure (TTF) and OS were 3.7 and 16.2 months, respectively. Salivary gland and nasopharyngeal cancer achieved relatively higher ORR (25.0 and 36.4%, respectively). On analysis by primary site, nasopharyngeal cancer showed a significantly better TTF and OS than the other primary sites. On analysis by histological findings, no significant difference in TTF and OS was observed between non-SCC and SCC.Nivolumab for cancers involving the salivary gland/nasopharynx and non-SCC histology showed comparable efficacy to that in CheckMate 141. This result indicates that nivolumab may be effective even for patients not included in CheckMate 141.

Significance Guinea yam is an important staple tuber crop in West Africa, where it contributes to the sustenance and sociocultural lives of millions of people. Understanding the genetic diversity of Guinea yam and its relationships with wild relatives is important for improving this important crop using genomic information. A recent genomics study proposed that Guinea yam originated from a wild relative, the rainforest species Dioscorea praehensilis . Our results based on sequencing of 336 Guinea yam accessions do not support this notion; rather, our results indicate a hybrid origin of Dioscorea rotundata from crosses between the savannah species Dioscorea abyssinica and D. praehensilis.

We constructed recombinant inbred lines (RILs) between a Japanese and a Taiwanese landrace of foxtail millet and employed next-generation sequencing, such as flexible ddRAD-seq and Nanopore sequencing to identify the candidate genes involved in the crop evolution of foxtail millet. We successfully constructed a linkage map using flexible ddRAD-seq with parents and RILs and detected major QTLs for each of three traits: leaf sheath colors, spikelet-tipped bristles (stb), and days to heading (DTH). (1) For leaf sheath colors, we identified the C gene on chromosome IV. (2) We identified a homeobox (HOX14) gene for stb on chromosome II, which shows homology with HvVrs1 in barley. (3) Finally, we identified a QTL with a large effect on DTH on chromosome II. A parent of the RILs from Taiwan and Yugu1 had a Harbinger-like TE in intron 3 of this gene. We also investigated the geographical distribution of the TE insertion type of this gene and found that the insertion type is distributed in the northern part of East Asia and intensively in South and Southeast Asia, suggesting that loss/reduction of function of this gene plays an important role in spreading into the northern part of East Asia and subtropical and tropical zones.

Significance Guinea yam is an important staple tuber crop in West Africa, where it contributes to the sustenance and sociocultural lives of millions of people. Understanding the genetic diversity of Guinea yam and its relationships with wild relatives is important for improving this important crop using genomic information. A recent genomics study proposed that Guinea yam originated from a wild relative, the rainforest species Dioscorea praehensilis. Our results based on sequencing of 336 Guinea yam accessions do not support this notion; rather, our results indicate a hybrid origin of Dioscorea rotundata from crosses between the savannah species Dioscorea abyssinica and D. praehensilis., White Guinea yam (Dioscorea rotundata) is an important staple tuber crop in West Africa. However, its origin remains unclear. In this study, we resequenced 336 accessions of white Guinea yam and compared them with the sequences of wild Dioscorea species using an improved reference genome sequence of D. rotundata. In contrast to a previous study suggesting that D. rotundata originated from a subgroup of Dioscorea praehensilis, our results suggest a hybrid origin of white Guinea yam from crosses between the wild rainforest species D. praehensilis and the savannah-adapted species Dioscorea abyssinica. We identified a greater genomic contribution from D. abyssinica in the sex chromosome of Guinea yam and extensive introgression around the SWEETIE gene. Our findings point to a complex domestication scenario for Guinea yam and highlight the importance of wild species as gene donors for improving this crop through molecular breeding.

Background: Platinum-containing doublet chemotherapy regimens are generally considered the standard first-line systemic therapy for recurrent or metastatic (R/M) nasopharyngeal cancer (NPC). Gemcitabine (GEM) plus cisplatin (CDDP) has become a standard therapy based on a phase 3 study in several countries, yet this regimen sometimes affects quality of life due to nausea or appetite loss. Here, we present the manageable toxicity and promising activity of paclitaxel + carboplatin + cetuximab (PCE) therapy for R/M NPC. Materials and Methods: We conducted a retrospective review of patients with R/M NPC who were treated with PCE from 2013 to 2019 at the National Cancer Center East, Kashiwa, Japan. PCE consisted of PTX 100 mg/m2 on days 1 and 8; CBDCA area under the blood concentration-time curve (AUC) 2.5 on days 1 and 8, repeated every 3 weeks; and cetuximab at an initial dose of 400 mg/m2, followed by 250 mg/m2 weekly, as reported in the paper. Results: Fourteen patients were identified, consisting of 10 males and 4 females with a median age 59.6 years (range, 43-74). Among the 12 of 14 patients assessed for efficacy, overall response rate was 58.3%, with 2 complete responses and 5 partial responses. On median follow-up of 23.8 months, median overall survival was not reached with observed death events of 2. Median PFS was 4.1 months (95% CI, 2.6-5.6 months). Two patients experienced disease progression during cetuximab maintenance and restarted PCE treatment, then achieved partial response again. The most common grade 3 or 4 adverse events were neutropenia (21.4%) and skin reaction (14.3%). No treatment-related death was observed. Conclusion: Although the number of study population was small, our results suggest that PCE is feasible and potentially effective for R/M NPC, with a 58.3% response rate and 4.1-month PFS. Further prospective evaluation is warranted.

White Guinea yam (Dioscorea rotundata) is an important staple tuber crop of West Africa. However, its origin remains unclear. In this study, we re-sequenced 336 accessions of white Guinea yam and compared them with the sequences of the wildDioscoreaspecies using an improved reference genome sequence ofD. rotundata. Our results suggest a hybrid origin of white Guinea yam from crosses between the rainforest wild speciesD. praehensilisand the savannah-adaptedD. abyssinica. We identified a higher genomic contribution fromD. abyssinicain the sex chromosome of Guinea yam and an extensive introgression around theSWEETIEgene. Our findings point to a complex domestication scenario for Guinea yam and highlight the importance of wild species as gene donors for improvement of this crop through molecular breeding.

Background It is important to consider that prolonged opioid use or opioid overuse for a patient who completed radiation therapy (RT) can have harmful effects. In 2018, pharmacists working with oncologists at outpatient clinics conducted an opioid de-escalation program for HNC patients who completed radiation therapy (RT) at the National Cancer Center Hospital East (NCCHE). The aim of this retrospective study was to evaluate the feasibility of a pharmacist-led opioid de-escalation (PLODE) program for HNC patients by comparing the outcomes of patients who participated in the PLODE program and those who did not. Methods This time-series analysis compared the outcomes of patients who participated in the PLODE program after CRT completion between June 2018 and February 2019 and those of patients who completed CRT between June 2017 and March 2018 and did not participate in the program. The PLODE program consisted of (1) number of opioid rescues, (2) patient’s complaints and (3) purpose of opioid use to patients based on the WHO Pain Ladder. Results Sixty-one patients completed CRT between June 2018 and February 2019. Of these 61 patients, 16 (26%) used opioids at the time of CRT completion and participated in the PLODE program. Ninety-three patients completed CRT between June 2017 and March 2018, and 32 patients (34%) used opioids at the time of CRT completion; these patients were evaluated as the control group. Patients who participated in the PLODE program discontinued opioids statistically earlier than those in the control group (median time to opioid discontinuation 11 days vs 24.5 days, HR 0.31, 95% CI 0.16-0.60, p Conclusions The study showed the feasibility of a PLODE program for HNC patients who completed CRT. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Background In the CheckMate 141 trial, nivolumab, a human IgG4 anti-PD-1 monoclonal antibody, provided a significant improvement in overall survival (OS) of patients with recurrent or metastatic squamous cell carcinoma (SCC) of the oral cavity, pharynx, or larynx. In Japan, nivolumab has been approved for platinum pretreated head and neck cancers regardless of histologic type and subsite. In other words, nivolumab is also available for non-SCC and subsites of head and neck cancer which were not included in the CheckMate 141 trial. However, the efficacy of nivolumab for cancers arising from these other subsites has not been clarified. Methods: We retrospectively reviewed data for 122 consecutive patients with head and neck cancers treated with nivolumab in our institution between March 2017 and December 2018. Patients with head and neck SCC of oral, oropharyngeal, hypopharyngeal, and laryngeal cancer were excluded. Final analysis of the study population was restricted to those 37 patients with non-SCC histological type or SCC arising from other subsites of the head and neck. Results: Median age was 57 years (range 30 to 77). Primary sites were nasopharynx/sinonasal/salivary/other regions of the head and neck (n = 8/10/8/11). Nineteen patients had SCC and 18 had non-SCC. In patients who could be evaluated by RECIST (n = 32), objective response rate was 18.8% in the total study population, 37.5% in NPC, 10.0% in sinonasal cancer and 25.0% in salivary cancer. Median OS and time to treatment failure (TTF) in the total study population was 12.1 months and 2.3 months, respectively. Median TTF in NPC patients was better than that in patients with other primary sites (7.6 vs. 2.5 months, p = 0.016). There was a trend toward improved TTF in SCC group compared to non-SCC group (4.2 vs. 2.4 months, p = 0.31). Conclusion: Nivolumab showed favorable efficacy in head and neck cancers arising from subsites which were not included in the CheckMate141 trial, especially NPC patients.

健康づくりの目的は、健康増進のみならず生活の質(Qualify of life: QOL)の向上にある。メタボリックシンドローム (metabolic syndrome: MetS)は生活習慣と密接に関連しており、健康習慣の変容によって改善が可能である一方、病態が進行すると日常生活活動の制限につながりQOL は低下する。本研究では、食行動変容によるMetS の病態改善がQOL の変化にどのように影響しているかを示す構造を明らかにすることを目的とした。「天使健康・栄養クリニック」を受講した平均年齢60.8 歳の87 名(男性35 名、女性52 名)を対象に、トランスセオレティカルモデル(Transtheoretical Model: TTM)に基づいて、3ヶ月間教育的に指導・支援を行った。その結果、食行動変容段階得点やその他の健康関連指標値が高まり、食物エネルギー摂取量が低下し、MetS 診断指標値が改善するとともにQOL 得点が上昇した。QOL の向上には、指導・支援後の食行動社会的支援 (食行動social support: 食行動SS) 得点、腹囲変化率、拡張期血圧変化率が回帰された。さらに、QOL の向上には、食行動SS を介した食行動変容段階の向上によって改善した健康習慣指数(Health practice index: HPI)や腹囲の変化が関連している構造モデルが得られた。MetS の改善がQOL の向上に関連するとともにその向上に至る構造が明らかになった。, The purpose of health promotion is not only to enhance health but also to improve the quality of life (QOL). Metabolic syndrome (MetS) can be alleviated through a change in health habits as it is closely linked to lifestyle. However, when left untreated, MetS will limit the daily activities of the affected individual and reduce his/her QOL. This study aims to analyze the structural equation modeling of relationships between QOL, eating behavior change, and MetS. We recruited 87 individuals (35 males, 52 females; mean age 60.8 years) who attended a program conducted by Tenshi Health and Nutrition Clinic. The participants received educational intervention for 3 months; the intervention was based on the transtheoretical model of behavior change. The intervention resulted in improved QOL scores, along with an improvement in the stage of eating behavior change, increased health-related indicator levels, decreased dietary energy intake, and improved MetS index level. After intervention, improvement in QOL was correlated with the scores of social support (SS) for eating behavior change (eating behavior SS) as well as with the changing rates of abdominal circumference and diastolic blood pressure. These results indicated a structural equation modeling that QOL improvement was related to changes in health practice index and abdominal circumference. Both changes resulted from improvement in the stage of eating behavior facilitated by improved eating behavior SS. Further research is required to elucidate the structural modeling involved in the enhancement of QOL associated with the alleviation of MetS.

「天使健康栄養クリニック」は、地域住民を対象にメタボリックシンドロームの予防・改善を目的として開催されている。本クリニックでは、講話並びに個人面談によって健康教育と変容支援を行っている。2008 年度および2009 年度に本クリニックに参加し修了した人たちを対象として、4ヶ月間における運動行動、ストレス対処・休養行動および食行動の変容について、個別に検討した。クリニック全8回のうち1、3、5、7回目に計4回、対象者に実施した質問紙調査から行動変容ステージ(得点)を評価した結果、3種の健康行動は、平均的には第1回目に比べて4回目には行動変容ステージ(得点)が高まり変容がみられた。しかし、個々人でみると第1回目から4回目までの変容は直線的ではない対象者も多かった。第1回目に比べて4回目に変容ステージ(得点)が高まった対象者の他に変化しなかった者、低下した者も見られたので、そのような違いの要因を面談記録から推察した。運動行動変容に関する事例検討から、上昇・改善者では、歩行を中心に運動が継続されていたが、継続しようという強い意欲と支援がうまく関連していたと考えられる。, The Tenshi Health and Nutrition Clinic is a health awareness and guidance course offered to local residents for the prevention and alleviation of metabolic syndrome. The clinic, which is run over eight non-consecutive days, comprises lectures and personal interviews, and aims to help participants improve health awareness and progress through the stages of behavioral change. In this study, changes in exercise behavior, stress management and resting behavior, and dietary behavior were individually assessed over a four-monthe period in participants who completed the clinic in 2008 and 2009. Scores indicative of the stage of behavioral change (behavioral change scores) were obtained from questionnaires completed by participants on days one, three, five, and seven of the clinic. On an average, the behavioral change scores for all three types of health-improving behavior were higher in the fourth questionnaire survey than in the first one, suggesting that the participants had progressed through the stages of behavioral change. However, the results of the four questionnaire surveys showed that the time-dependent changes in health-improving behavior are not linear for many participants. When the behavioral change scores of the fourth survey were compared with those of the first survey, they were higher in some participants, but lower or unchanged in others. Information obtained from individual interviews indicated that continuous effort was made to maintain an exercise routine, in particular walking, by participants who made progress in changing their behaviors. The results suggest that with regard to participants who improved their exercise behavior, the support provided was positively linked with the strong will to continue an exercise routine.

地域住民を対象にメタボリックシンドローム(MetS)予防を目的とした健康教室「天使健康栄養クリニック」(以下、クリニック)を開催している。本研究では、参加者個々人の運動行動の変容段階に着目し、変容段階に合わせた運動実施の支援による体力向上とMetS予防・改善の関連について明らかにすることを目的として、教室終了時に運動行動変容段階を実行期以上に高めた者と高めなかった者とで比較検討を行なった。対象は、クリニックを受講し修了した58名(男性22 名、女性36 名)であり、運動行動変容段階、自己効力感(SE)や、ソーシャルサポート(SS)、体力、身体組成、血液検査値、栄養摂取量等を測定した。その結果、運動行動変容段階を実行期以上に高めた参加者は、実行期まで至らなかった参加者に比べて、SE 得点やSS得点が高まり、体力指標が向上し、腹囲や生化学検査値、血圧などMetS診断指標値の改善度合いが高かった。クリニックでは、運動実施以外に食事と休養の行動変容を指導・支援しているため、食事内容が改善するなど生活全般が健康的に変容したが、運動を日常的に継続して実行できるようになることで、体力が向上すると同時に、MetS 診断指標値の改善が進むことが示唆された。, The Tenshi Health and Nutrition Clinic is a health awareness and guidance course offered to local residents for the prevention and alleviation of metabolic syndrome. In this study, we focused on the stages of exercise behavior changes in individual participants to reveal the association of improvement in physical fitness, achieved by stage-matched exercise guidance, with prevention and alleviation of metabolic syndrome. Participants (n=58; 22 men, 36 women) were divided into two groups according to whether they had reached the action stage in the behavior change model by the end of the clinic(A-group or B-group). The stage of change in exercise behavior, self efficacy (SE) and social support (SS) scores, physical fitness, body composition, blood test results, and nutrient intake were compared between the groups. SE and SS scores and physical fitness indices were higher in participants who reached at least the action stage (A-group) than in those who had not (B-group). In addition, improvements in the values of diagnostic indices of metabolic syndrome, such as abdominal circumference, biochemical test results, and blood pressure, were more prominent in A-group than in B-group. The clinic offered consultation and guidance on diet and resting, as well as on exercise. Thus, overall lifestyle including eating habits improved among the participants. This study shows that adopting a daily and continuous exercise behavior enhances physical fitness and improves the values of diagnostic indices in metabolic syndrome.

Soybean [Glycine max (L) Merrill] is one of the most important leguminous crops and ranks fourth after to rice, wheat and maize in terms of world crop production. Soybean contains abundant protein and oil, which makes it a major source of nutritious food, livestock feed and industrial products. In Japan, soybean is also an important source of traditional staples such as tofu, natto, miso and soy sauce. The soybean genome was determined in 2010. With its enormous size, physical mapping and genome sequencing are the most effective approaches towards understanding the structure and function of the soybean genome. We constructed bacterial artificial chromosome (BAC) libraries from the Japanese soybean cultivar, Enrei. The end-sequences of approximately 100,000 BAC clones were analyzed and used for construction of a BAC-based physical map of the genome. BLAST analysis between Enrei BAC-end sequences and the Williams82 genome was carried out to increase the saturation of the map. This physical map will be used to characterize the genome structure of Japanese soybean cultivars, to develop methods for the isolation of agronomically important genes and to facilitate comparative soybean genome research. The current status of physical mapping of the soybean genome and construction of database are presented.

メタボリックシンドローム(メタボ)予防を目指した「天使健康栄養クリニック」を2006年と2007年に開設し、地域住民58名を対象に食事や運動、健康行動への介入支援指導を約3ヶ月間に渡って行い、腹囲や血圧、血中成分などのメタボ関連指標の変化を調べた。介入前後での平均値を比較すると、男女間で若干の違いがあるものの、腹囲と血糖が有意に低下し、血圧と中性脂肪も低下傾向が認められた。メタボの診断基準からメタボおよび予備群の判定を行い、人数を比較したところ、3ヶ月の介入によってメタボ該当者は10名から9名に、予備群は31名から28名に、それぞれ減少したことがわかった。これらの結果から、本クリニックはメタボの予防・改善に一定の効果があると結論した。なお、介入の効果には大きな個人差が見られたので、今後はこれらを考慮した介入方法の検討が必要であろう。, Tenshi Health and Nutrition Clinic aimed to identify methods for preventing metabolic syndrome by conducting studies for 3 months in 2006 and 2007. A total of 58 participants underwent medical examinations, including measurement of waist circumference, blood pressure, and blood biochemistry, before and after a 3 month support program. This program consisted of lectures and counseling for improving dietary and physical activities. The program decreased the waist circumference and blood glucose, blood pressure, and blood triglyceride levels of the participants to a certain extent, thereby leading to a slight decrease in the number of patients diagnosed with metabolic syndrome. Thus, Tenshi Health and Nutrition Clinic have developed a program for the prevention of metabolic syndrome, although further modifications of this program may be necessary.

インスリン抵抗性の上流に位置する内臓脂肪型肥満は、メタボリックシンドロームの必須条件であり、BMI による量的肥満とは区別される。減量に伴う肥満指標と血中因子との関連を検討し、肥満指標を規定する食事因子を明らかにすることを目的にした。天使健康栄養クリニックを受講した平均年齢59.1歳の58名(男性22、女性36)を対象に、3ヶ月間の栄養と運動指導を行った。開始時及び3 ヶ月指導後に身体計測、血圧測定、採血と血液生化学検査、連続3日間の撮影法による食事調査を行った。3ヶ月で体重は男性で3.5%、女性で3.3%減少し、体脂肪率も減少した。腹囲は男性93.5 cm から90.1、女性92.6 cm から89.7と減少した。摂取エネルギーは男性34.5kcal/kg/day から29.9, 女性33.0から29.1と減少した。血中中性脂肪とHOMA 指数の変化には腹囲が回帰されたが、体重との関連は認めなかった。腹囲減少率には、体重とは独立して食事脂質量が回帰され、エネルギー補正後も同様であった。メタボリックシンドロ-ムのKey Factor である腹囲には、食事由来のエネルギー摂取量とは独立して脂質摂取総量の寄与が大きい可能性が示唆され、今後の検討に繋がる知見であった。, Visceral fat accumulation, upstream of insulin resistance, is the characteristic condition of metabolic syndrome; this feature distinguishes metabolic syndrome from obesity assessed using body mass index. In the present study, we aimed to evaluate weight loss associated correlations between obesity indices and factors in blood to identify the dietary factors that regulate the obesity indices. Dietary and exercise guidance was provided for 3 months to 58 participants (22 male, 36 female;mean age, 59.1 years) who attended a program at Tenshi Health and Nutrition Clinic to prevent and/or improve metabolic syndrome. Measurement of body size and blood pressure, blood collection and biochemical analysis, and a 3 day (consecutive) dietary survey were performed before and after the participants received guidance. After the program, the weights of the male and female participants had decreased by 3.5% and 3.3% , respectively, and the body fat percentage of the participants had also decreased. The average abdominal circumference of the male participants was reduced from 93.5 cm to 90.1 cm, and that of female participants reduced from 92.6 cm to 89.7 cm. The average amount of energy consumed by the male participants reduced from 34.5 to 29.9 kcal/kg・day-1 and that of the female participants was also reduced from 32.9 to 28.9 kcal/kg・day-1. The amount of calories consumed at lunch, dinner, and snack time decreased in the male group, while those consumed at dinner and snack time decreased in the female group. Consumption of sugar was reduced while that of fruit was increased in the male group: while consumption of grain and fat was reduced in the female group. Changes in triglyceride concentration in blood and the HOMA index scores correlated with the changing rate of abdominal circumference, but did not correlate with the weight changing rate. The reduction rate of abdominal circumference was independent of weight, but was correlated with the reduction in the amount of fat present in meals. This rate remained unchanged after energy intake correction. These findings suggest that abdominal circumference, which is believed to be a key factor of metabolic syndrome, is influenced by the total amount of fat contained in meals, but is independent of caloric intake, this possibility must be further studied in further studies.

The genomic sequences derived from rice centromeric regions were analyzed to facilitate the comprehensive understanding of the rice genome. A rice centromere-specific satellite sequence, RCS2/ TrsD/CentO, was used to screen P1-derived artificial chromosome (PAC) and bacterial artificial chromosome (BAC) genomic libraries derived from Oryza sativa L. ssp. japonica cultivar Nipponbare. Physical maps of the centromeric regions were constructed by DNA fingerprinting methods and the aligned clones were analyzed by end sequencing. BLAST analysis revealed the composition of genes, centromeric satellites and other repetitive elements, such as RIRE7/CRR, RIRE8, Squiq, Anaconda, CACTA and miniature inverted-repeat transposable elements. Fiber-fluorescent in situ hybridization analysis also indicated the presence of distinct clusters of RCS2/TrsD/CentO satellite interspersed with other elements, instead of a long homogeneous region. Several expressed genes, sequences representative of ancestral organellar insertions, relatively long simple sequence repeats (SSRs), and sequences corresponding to 5S and 45S ribosomal RNA genes were also identified. Thirty-one gene sequences showed high-similarity to rice full-length cDNA sequences that had not been matched to the published rice genome sequence in silico. These results suggest the presence of expressed genes within and around the clusters of RCS2/TrsD/CentO satellites in unsequenced centromeric regions of the rice chromosomes.

Rice, one of the world's most important food plants, has important syntenic relationships with the other cereal species and is a model plant for the grasses. Here we present a map-based, finished quality sequence that covers 95% of the 389 Mb genome, including virtually all of the euchromatin and two complete centromeres. A total of 37,544 non-transposable-element-related protein-coding genes were identified, of which 71% had a putative homologue in Arabidopsis. In a reciprocal analysis, 90% of the Arabidopsis proteins had a putative homologue in the predicted rice proteome. Twenty-nine per cent of the 37,544 predicted genes appear in clustered gene families. The number and classes of transposable elements found in the rice genome are consistent with the expansion of syntenic regions in the maize and sorghum genomes. We find evidence for widespread and recurrent gene transfer from the organelles to the nuclear chromosomes. The map-based sequence has proven useful for the identification of genes underlying agronomic traits. The additional single-nucleotide polymorphisms and simple sequence repeats identified in our study should accelerate improvements in rice production.

We constructed physical maps of rice chromosomes 1, 2, and 6-9 with P1-derived artificial chromosome (PAC) and bacterial artificial chromosome (BAC) clones. These maps, with only 20 gaps, cover more than 97% of the predicted length of the six chromosomes. We submitted a total of 193 Mbp of non-overlapping sequences to public databases. We analyzed the DNA sequences of 1316 genetic markers and six centromere-specific repeats to facilitate characterization of chromosomal recombination frequency and of the genomic composition and structure of the centromeric regions. We found marked changes in the relative recombination rate along the length of each chromosome. Chromosomal recombination at the centromere core and surrounding regions on the six chromosomes was completely suppressed. These regions have a total physical length of about 23 Mbp, corresponding to 11.4% of the entire size of the six chromosomes. Chromosome 6 has the longest quiescent region, with about 5.6 Mbp, followed by chromosome 8, with quiescent region about half this size. Repetitive sequences accounted for at least 40% of the total genomic sequence on the partly sequenced centromeric region of chromosome 1. Rice CentO satellite DNA is arrayed in clusters and is closely associated with the presence of Centromeric Retrotransposon of Rice (CRR)- and RIce RetroElement 7 (RIRE7)-like retroelement sequences. We also detected relatively small coldspot regions outside the centromeric region; their repetitive content and gene density were similar to those of regions with normal recombination rates. Sequence analysis of these regions suggests that either the amount or the organization patterns of repetitive sequences may play a role in the inactivation of recombination.

A basidiomycete, Coprinus sp. SF-1, was found to produce an L-Trp-oxidizing enzyme by screening from the culture collection of our laboratory. After solubilization by 1 M NaSCN from the particulate fraction of disrupted cells of the strain, the enzyme was purified about 76-fold to essential homogeneity. The enzyme had a molecular mass of about 420 kDa and the subunit molecular mass was 68 kDa. The enzyme contained 1 mol of non-covalently bound FAD per mol of the subunit. It catalyzed the simultaneous reactions of oxidative deamination and oxygenative decarboxylation of L-Trp to form indolepyruvic acid and indole-3-acetamide, the former of which was further oxidized to indole-3-acetic acid. The molar ratio of the respective reaction products was about 9:1. The enzyme specifically oxidized L-Trp, and slightly acted on L-Phe and L-Tyr. The Km for L-Trp was about 0.5 mM in both oxidase and oxygenase reactions. Thus, the enzyme is a novel one and was tentatively designated "L-Trp oxidase (deaminating and decarboxylating)". The optimum pHs of oxidase and oxygenase activities were 7.0 and 9.0, respectively. The optimum temperatures of both activities were 50 degrees C. The enzyme was stable at pH 6.0-10.5 and below 50 degrees C, and at 4 degrees C for 1 year.

This study was carried out to elucidate the prevalence of intestinal helminthic infections in rural communities in Nepal. Of 231 inhabitants randomly sampled in Kotyang and Judigaun, 140 (60.6%) were found to be infected with some soil-transmitted helminths. The highest prevalence was observed in hookworm infection (52.8%), followed by Trichuris trichiura (18.6%) and Ascaris lumbricoides (11.3%) infections. Some inhabitants harboured Vampirolepis nana and liver fluke. The female group aged 60 years old and more showed significantly higher T. trichiura infection rate than the male group with the same age (p

はじめに: 飲水の制限は, 透析の予後を左右する循環器系の合併症を予防する上で重要である. しかし, 透析を受けている患者の中には, この飲水制限が不良である者が少なくない. そこで, 透析患者における飲水制限とパーソナリティ上の関係について, MMPI (Minnesota Multiphasic Personality Inventory) を用いて調査した.対象と方法: 清湘会のクリニックにおいて慢性維持血液透析を受けている患者約398人のうち, 中-日の体重増加がdry weightの5%以上ある51名 (男性: 34名, 女性: 17名) を体重管理の不良な例 (不良群) とし, 中-日の体重増加がdry weightの3%以下の33名 (男性: 16名, 女性: 17名) を良好な例 (良好群) とした.これらの透析患者にMMPI (原法の新日本語版, 三京房, 京都) を施行し, 不良, 良好の2群の間で各尺度の平均値について男女別に集計を行い, 比較を行った. MMPIの日本での標準化に際して対象とした健常成人1,022名 (男性: 500名, 女性: 522名) との間でも比較を行った.結果: 不良群は良好群に比し, 不安, 身体的愁訴に関係する尺度 (Hs, D, Hy, Pdなど) で高い値をとる傾向が認められたが, 有意な差はなかった. 正常成人に比べると, 不良群, 良好群ともにL, Hs, D, Hy, Esの尺度で有意に高値を示した.考察: 今回示された不良群, 良好群にともに認められたHs, D, Hyの高値は, 透析患者の抑鬱状況と身体的拘りを示唆する. この3つの尺度の上昇はneurotic triadと呼ばれ, 透析患者の神経症的状態を示すものと考えられる. 有意差は認められなかったが, 不良群ではこれらの尺度の得点が良好群より高く, 神経症的傾向が強いようであった.追加尺度のEsの低値は自我の脆弱性に通じるもので, 透析を受ける患者の精神的脆さを示しているといえよう.

Stimulation of systemic antigen-specific IgE production plays an important role in the mediation of food allergy; however, the mechanism of IgE production against food antigens is not fully understood. The development of relevant animal models may help to elucidate the pathogenesis of food allergy. We here show that DBA/2 mice receiving a casein diet without any adjuvant produced high levels of IgE specific for casein, accompanied by predominant Th2-like responses in liver lymphocytes, mesenteric lymph node cells and spleen cells. This model of IgE production produced by feeding protein antigen as a constituent of the diet can be applied to investigate the mechanism of IgE production and to develop reagents for controlling food allergy.

We have investigated the effects of CP-99,994 [(+)-(2s,3s)-3-(2-methoxybenzylamino)-2-phenylpiperidine], a tachykinin NK1 receptor antagonist, HOE 140 (D-Arg[Hyp3,Thi5,D-Tic7,Oic8]bradykinin), a bradykinin B2 receptor antagonist, and ketotifen (4-(1-methyl-4-piperidylidene)4 H-benzo[4,5]cycloheptal[1,2-b]thiophen-10(9H)-one hydrogen fumarate), a histamine H1 receptor antagonist with mast cell-stabilizing properties, on microvascular leakage induced by gaseous formaldehyde. Extravasation of Evans blue dye into airway tissues was used as an index of airway microvascular leakage. Leakage of dye in the trachea and main bronchi increased significantly in a concentration-dependent fashion after 10 min inhalation of formaldehyde (5-45 parts per million (ppm)). The airway response induced by 10 min inhalation of 15 ppm formaldehyde (trachea: 119.5 +/- 13.9 ng/mg, n = 7; main bronchi: 139.6 +/- 7.9 ng/mg, n = 7) was abolished by the administration of CP-99,994 (3 and 6 mg/kg i.v.), but not by the administration of HOE 140 (0.65 mg/kg i.v.) nor ketotifen (1 mg/kg i.v.). The increase in vascular permeability induced by formaldehyde in the rat airway was mediated predominantly by NK1 receptor stimulation. Activation of bradykinin receptors and mast cells did not appear to play an important role in this airway response.

This study was designed to investigate the patient's recognition of changes in facial profile due to orthognathic surgery. The results of questionnaires were summarized and analyzed in relation to cephalometric data.The subjects consisted of forty-three posttreatment patients (13 males and 30 females) with mandibular prognathism, , who had undergone orthognathic surgery at Hiroshima University Dental Hospital. In this study, patient's recognition of improvement in facial profile was summarized in relation to morphologic changes associated with orthognathic surgery by means of Spearman's correlation analysis.The results were as follows:1. Before treatment, eighty-eight percent of patients were anxious about disharmony of the facial profiles, and the degree of anxiousness was severe in half of them. As for facial areas, the lower lip and chin were their greatest concern.2. After treatment, eighty-four percent of patients recognized improvement in facial profile, and sixty-three percent of patients assessed that their profiles were improved more substantially than expected before treatment. As for facial parts, more than seventy percent of patients mainly recognized improvement in lower lip and chin.3. The patient's recognition of improvement in facial profile, especially chin, exhibited a significantly positive correlation with the amount of mandibular setback during treatment.These results suggested that most patients assessed that improvement in facial profile was achieved by orthognathic surgery. It is shown that their recognition of improvement in their facial profiles is significantly correlated with the amount of mandibular setback.

Rice (Oryza sativa L.) is a model organism for the functional genomics of monocotyledonous plants since the genome size is considerably smaller than those of other monocotyledonous plants. Although highly accurate genome sequences of indica and japonica rice are available, additional resources such as full-length complementary DNA (FL-cDNA) sequences are also indispensable for comprehensive analyses of gene structure and function. We cross-referenced 28.5K individual loci in the rice genome defined by mapping of 578K FL-cDNA clones with the 56K loci predicted in the TIGR genome assembly. Based on the annotation status and the presence of corresponding cDNA clones, genes were classified into 23K annotated expressed (AE) genes, 33K annotated non-expressed (ANE) genes, and 5.5K non-annotated expressed (NAE) genes. We developed a 60mer oligo-array for analysis of gene expression from each locus. Analysis of gene structures and expression levels revealed that the general features of gene structure and expression of NAE and ANE genes were considerably different from those of AE genes. The results also suggested that the cloning efficiency of rice FL-cDNA is associated with the transcription activity of the corresponding genetic locus, although other factors may also have an effect. Comparison of the coverage of FL-cDNA among gene families suggested that FL-cDNA from genes encoding rice- or eukaryote-specific domains, and those involved in regulatory functions were difficult to produce in bacterial cells. Collectively, these results indicate that rice genes can be divided into distinct groups based on transcription activity and gene structure, and that the coverage bias of FL-cDNA clones exists due to the incompatibility of certain eukaryotic genes in bacteria.

Understanding the organization of eukaryotic centromeres has both fundamental and applied importance because of their roles in chromosome segregation, karyotypic stability, and artificial chromosome-based cloning and expression vectors. Using clone-by-clone sequencing methodology, we obtained the complete genomic sequence of the centromeric region of rice (Oryza sativa) chromosome 8. Analysis of 1.97 Mb of contiguous nucleotide sequence revealed three large clusters of CentO satellite repeats (68.5 kb of 155-bp repeats) and >220 transposable element (TE)–related sequences; together, these account for ∼60% of this centromeric region. The 155-bp repeats were tandemly arrayed head to tail within the clusters, which had different orientations and were interrupted by TE-related sequences. The individual 155-bp CentO satellite repeats showed frequent transitions and transversions at eight nucleotide positions. The 40 TE elements with highly conserved sequences were mostly gypsy-type retrotransposons. Furthermore, 48 genes, showing high BLAST homology to known proteins or to rice full-length cDNAs, were predicted within the region; some were close to the CentO clusters. We then performed a genome-wide survey of the sequences and organization of CentO and RIRE7 families. Our study provides the complete sequence of a centromeric region from either plants or animals and likely will provide insight into the evolutionary and functional analysis of plant centromeres.

We constructed physical maps of rice chromosomes 1, 2, and 6-9 with P1-derived artificial chromosome (PAC) and bacterial artificial chromosome (BAC) clones. These maps, with only 20 gaps, cover more than 97% of the predicted length of the six chromosomes. We submitted a total of 193 Mbp of non-overlapping sequences to public databases. We analyzed the DNA sequences of 1316 genetic markers and six centromere-specific repeats to facilitate characterization of chromosomal recombination frequency and of the genomic composition and structure of the centromeric regions. We found marked changes in the relative recombination rate along the length of each chromosome. Chromosomal recombination at the centromere core and surrounding regions on the six chromosomes was completely suppressed. These regions have a total physical length of about 23 Mbp, corresponding to 11.4% of the entire size of the six chromosomes. Chromosome 6 has the longest quiescent region, with about 5.6 Mbp, followed by chromosome 8, with quiescent region about half this size. Repetitive sequences accounted for at least 40% of the total genomic sequence on the partly sequenced centromeric region of chromosome 1. Rice CentO satellite DNA is arrayed in clusters and is closely associated with the presence of Centromeric Retrotransposon of Rice (CRR)- and RIce RetroElement 7 (RIRE7)-like retroelement sequences. We also detected relatively small coldspot regions outside the centromeric region; their repetitive content and gene density were similar to those of regions with normal recombination rates. Sequence analysis of these regions suggests that either the amount or the organization patterns of repetitive sequences may play a role in the inactivation of recombination.

Measurements of %Fat, nutrient intake and maximal aerobic power (MAP) were carried out on Nepalese to clarify the cause of obesity attended with modernization. One hundred thirty-two males (KV) who have a natural living style, 20-84 years of age, in rural district and 237 males who have a living style affected by the rapid urbanization, in surburban district were selected as subjects. The subjects of surburban district were divided into two groups. One of them included 147 farmers (BF) who engage in not mechanized farming, 20-73 years of age. Another group included 90 students and wage laborers (BNF) who go to and from Kathmandu (the capital of Nepal), 20-57 years of age. %Fat was estimated from skinfold thickness according to the method of Nagamine (1975). The survey for the nutrient intake was carried out by the 24-hour recall method to obtain the individual food consumption using the food models. Measurement of MAP was made indirectly by the modified of Margaria et al (1965). The main results are summarized as follows. 1) Mean %Fat and the appearance rates of obesity in each age group showed high values in following order: BNF greater than BF greater than KV. 2) Mean caloric intake in KV was higher than those in BF and in BNF an almost all age groups and no significant difference was found between BF and BNF in all age groups. 3) No significant differences in mean fat intake and in mean animal fat intake among all groups were found in almost all age groups.(ABSTRACT TRUNCATED AT 250 WORDS)

An assay of apolipoproteins (Apo) C-II, C-III and E in human sera by single radial immunodiffusion (SRID) is described. The procedure involves pretreatment of the serum sample with surfactant to facilitate diffusion of very low density lipoproteins in agarose. This allowed measurement of apolipoproteins in lipidemic sera by SRID in agarose gel. The intraplate coefficient of variation was less than 2.5%, and the interplate coefficient of variation, less than 3.0%. Correlation with double-antibody radioimmunoassay produced the following coefficients of correlation: gamma = 0.9931 (n = 17) for Apo C-II, gamma = 0.9221 (n = 33) for Apo C-III, and gamma = 0.9340 (n = 17) for Apo E.