Regulator of Awn Elongation 3, an E3 ubiquitin ligase, is responsible for loss of awns during African rice domestication.

Two species of rice have been independently domesticated from different ancestral wild species in Asia and Africa. Comparison of mutations that underlie phenotypic and physiological alterations associated with domestication traits in these species gives insights into the domestication history of rice in both regions. Asian cultivated rice, Oryza sativa, and African cultivated rice, Oryza glaberrima, have been modified and improved for common traits beneficial for humans, including erect plant architecture, nonshattering seeds, nonpigmented pericarp, and lack of awns. Independent mutations in orthologous genes associated with these traits have been documented in the two cultivated species. Contrary to this prevailing model, selection for awnlessness targeted different genes in O. sativa and O. glaberrima. We identify Regulator of Awn Elongation 3 (RAE3) a gene that encodes an E3 ubiquitin ligase and is responsible for the awnless phenotype only in O. glaberrima. A 48-bp deletion may disrupt the substrate recognition domain in RAE3 and diminish awn elongation. Sequencing analysis demonstrated low nucleotide diversity in a ~600-kb region around the derived rae3 allele on chromosome 6 in O. glaberrima compared with its wild progenitor. Identification of RAE3 sheds light on the molecular mechanism underlying awn development and provides an example of how selection on different genes can confer the same domestication phenotype in Asian and African rice.

[A Case of Resection of Locally Advanced Ascending Colon Cancer in an Elderly Patient with Parkinson's Disease].

The case presented here is of a man in his 80s who was attending the Department of Neurology for Parkinson's disease. He had a fever and visited the emergency department. A CT scan revealed a 10 cm mass in the hepatic flexure that was suspected of invading the duodenum, as well as numerous enlarged lymph nodes around the mass. A colonoscopy revealed a semi-peripheral type 3 tumor, and a biopsy showed adenocarcinoma(tub1-tub2). A right hemicolectomy was performed, and the tumor was located in the hepatic flexure of the ascending colon and was found to be in a mass with lymph nodes and adhesions to the duodenum. Due to the invasiveness of the surgery and the decrease in ADL, the patient's postoperative course required prolonged hospitalization. He was transferred to the hospital at POD33 and discharged at POD64. Due to his old age, adjuvant chemotherapy was not administered, and he is still alive 1 year after surgery with no recurrence. Even though his hospital stay was prolonged due to his decreased ADL, he is now able to return home. Aggressive resection may provide good results even in elderly patients.

[Two Cases of Aortitis Caused by Pegfilgrastim Administered during Chemotherapy for Breast Cancer].

Granulocyte colony-stimulating factor(G-CSF)is known to cause bone pain, headache, and fatigue as side effects. We experienced 2 cases of aortitis caused by pegfilgrastim(PEG-G)administration. Case 1: A 50s woman with breast cancer started FEC therapy with PEG-G as neoadjuvant chemotherapy. She developed a fever in the 38℃ range, and chest CT showed wall thickening in the aortic arch. She was diagnosed with aortitis and administration of prednisolone was started, and the fever resolved and the general condition improved dramatically. Case 2: A 70s woman was started TC therapy with PEG-G as adjuvant chemotherapy after surgery. Fever, anorexia, and epigastralgia appeared. A CT scan of the abdomen revealed thickening of the abdominal aortic wall from the thoracoabdominal transition area to the renal artery bifurcation. She was diagnosed with PEG-G-induced aortitis, and administration of prednisolone was started. The fever resolved and the pain disappeared. Although the symptoms of G-CSF-induced aortitis are nonspecific, it is relatively easy to diagnose by CT and should be considered when a fever develops after G-CSF administration.

Identification and functional characterization of a Siglec-7 counter-receptor on K562 cells.

Sialic acid (Sia)-binding immunoglobulin-like lectin 7 (Siglec-7) is an inhibitory receptor primarily expressed on natural killer (NK) cells and monocytes. Siglec-7 is known to negatively regulate the innate immune system through Sia binding to distinguish self and nonself; however, a counter-receptor bearing its natural ligand remains largely unclear. Here, we identified a counter-receptor of Siglec-7 using K562 hematopoietic carcinoma cells presenting cell surface ligands for Siglec-7. We affinity-purified the ligands using Fc-ligated recombinant Siglec-7 and diSia-dextran polymer, a strong inhibitor for Siglec-7. We then confirmed the counter-receptor for Siglec-7 as leukosialin (CD43) through mass spectrometry, immunoprecipitation, and proximity labeling. Additionally, we demonstrated that the cytotoxicity of NK cells toward K562 cells was suppressed by overexpression of leukosialin in a Siglec-7-dependent manner. Taken together, our data suggest that leukosialin on K562 is a counter-receptor for Siglec-7 on NK cells and that a cluster of the Sia-containing glycan epitope on leukosialin is key as trans-ligand for unmasking the cis-ligand.

Influence of ADHD, especially attention-deficit characteristics, on the course of alcohol-dependent individuals.

BACKGROUND: While several studies have revealed that neurodevelopmental disorders have a high probability of overlapping with substance use disorders, the effects of neurodevelopmental disorders on the courses of substance use disorders have hardly been examined. METHODS: This study targeted 637 alcohol-dependent individuals who received inpatient treatment and whose drinking situations were followed for 12 months after hospital discharge using mailed questionnaires. The comorbidity of psychiatric disorders and the characteristics associated with the neurodevelopmental disorders were assessed using several measurements at the time of hospital admission. The effects of neurodevelopmental disorders on the drinking courses of the subjects were then estimated. RESULTS: The presence of a current depressive episode or any anxiety disorder significantly lowered the abstinence rates during the follow-up period (p = 0.0195 and p = 0.0214, respectively). ADHD traits as assessed using the ADHD Self-report Scale (ASRS) predicted a significantly poorer abstinence rate (p = 0.0296). Similarly, attention-deficit characteristics assessed objectively through interviews predicted a significantly lower abstinence rate (p = 0.0346), and a sensitivity analysis enhanced these results (p = 0.0019). When the drinking patterns were classified into three groups, the subjects with attention-deficit characteristics had a significantly higher rate of "Recurrence" and lower rates of "Abstinence" and "Controlled drinking" (p = 0.013). In a multivariate proportional hazards analysis, the ASRS score was significantly correlated with the re-drinking risk (p = 0.003). CONCLUSION: ADHD traits had significant effects on not only abstinence rates, but also on drinking pattern. The presence of ADHD traits, especially attention-deficit characteristics, influenced the drinking courses of alcohol-dependent individuals after hospital treatment.

[Eight Cases of Breast Cancer That Relapsed More Than Ten Years after Initial Treatment].

Recurrence is more common for breast cancer than other solid tumors. In the last 5 years, we experienced 8 cases that relapsed more than 10 years after initial treatment. All cases were hormone-sensitive and HER2-negative. The Ki-67 percentage score was less than 15% in 7 cases. The age range at recurrence was 56-93 years(mean, 74.6 years), and the time to recurrence was 10-14 years and 20 or more years in 6 and 2 cases(mean, 14.6 years), respectively. The triggers for diagnosis were subjective symptoms, follow-up, and examination for other diseases in 3, 3, and 2 cases, respectively. The recurrence sites included the axilla, pleura/lung, liver/lung, skin, and chest wall in 3, 2, 1, 1, and 1 case, respectively. Treatment included an aromatase inhibitor(AI)and AI plus CDK4/6 inhibitor in 5 and 3 cases, respectively. The post-recurrence treatment period was 6-31 months(mean, 21.6 months), with 4 cases of PR, 3 cases of SD, and 1 case of death from other disease. There were 3 cases of axillary recurrence and 1 case each of neuropathic pain, upper limb edema, and local pain; all were alleviated by the treatment. In 2 cases, the pleural effusion decreased without chest tube drainage. Hormone receptor- positive late-relapse cases are generally highly therapeutically sensitive with favorable prognosis. In many cases, AI alone was selected considering patient age, side effects, treatment costs, and other factors.

[A Case in Which Inferior Vena Cava Stent Placement Was Effective for Inferior Vena Cava Stenosis Due to Metastatic Liver Tumor].

A 60s woman was diagnosed with cecal cancer with multiple liver metastases(final pathology was T4aN1M1[H1])and underwent ileocecal resection and D3 dissection. She did not wish for postoperative chemotherapy and surgical treatment of liver metastases. One and a half years after surgery, she developed extremity edema of lower legs and hypoalbuminemia, and she gained 20 kg. Contrast-enhanced CT showed stenosis of the inferior vena cava due to liver metastases, which was markedly improved the symptoms by placement of an inferior vena cava stent. Inferior vena cava stent placement is a minimally invasive treatment and can be an option as it can be expected to improve quality of life in some cases.

The conserved arginine residue in all siglecs is essential for Siglec-7 binding to sialic acid.

Siglecs are sialic acid (Sia)-binding immunoglobulin-like lectins; the majority of Siglecs functions as transmembrane receptors on the immune cells via Sia residues. Recently, a new Sia binding site in Siglec-7, termed site 2, where arginine (R) 67 was critical, was identified by computational modeling and biochemical analyses, relative to the primary Sia binding site, termed site 1, containing critical R124. Here, the presence of a new essential R94 residue, which is completely conserved among all identified Siglecs, was demonstrated. A mutation of R94 residue in Siglec-7 led to the disappearance of the Sia binding property, similar to a site 1 mutation (R124A). R94 is close to R67 in site 2, and site 2 mutations at either of them abolished the ligand-binding properties to both gangliosides and glycoproteins. These data suggest that, in addition to site 1, the conserved R residue among Siglecs in site 2 is another functional site.

Alcohol dependence severity determines the course of treatment-seeking patients.

BACKGROUND: While accumulating evidence suggests a relation between the severity of alcohol dependence and the risk of its recurrence, the impact of dependence severity on the course of the disorder has not been carefully evaluated. The present study examined the impact of several severity indices of alcohol dependence on the drinking course after inpatient treatment. METHODS: This prospective study was conducted over a 12-month period following alcohol treatment at a specialized hospital. A total of 712 consecutively admitted alcohol-dependent patients were targeted for enrollment at the time of their hospitalization, with 637 patients registered and followed. The characteristics and severity of the subjects were assessed using multiple methods at admission, with their course after discharge followed continuously using mailed questionnaires that queried them regarding their drinking behavior. RESULTS: Greater severity of dependence, assessed using the number of ICD-10 diagnostic criteria met, was associated with a lower rate of abstinence during the study period (p = 0.035). The rate of abstinence also decreased significantly as the baseline blood gamma-glutamyl transferase value and Alcohol Dependence Scale (ADS) score increased (p = 0.031 and p = 0.0002, respectively). In multivariate Cox proportional hazards analyses, the group with the most severe ADS scores had a significantly greater risk of relapse to drinking than the group with the least severe scores (HR = 2.67, p = 0.001). Dependence severity also associated with the drinking pattern; participants in both the controlled drinking group and the abstinence group had lower ADS scores at admission and a later age at first drinking (p = 0.001 and p < 0.001, respectively) than those with poorer drinking outcomes. CONCLUSIONS: The present study showed that more severe alcohol dependence predicts a poorer course after alcohol treatment, as reflected by findings on multiple measures. These results suggest that assessing the dependence severity at the outset of treatment could be useful both in predicting treatment outcome and targeting interventions to alcohol-dependent individuals who need additional support in their recovery.

Effects of Cognitive Behavioral Therapy for Insomnia on Subjective-Objective Sleep Discrepancy in Patients with Primary Insomnia: a Small-Scale Cohort Pilot Study.

BACKGROUND: Cognitive behavioral therapy for insomnia (CBT-I) is a first-line therapy for insomnia disorders. We assessed changes in discrepancies between subjective and objective sleep measures and correlations between discrepancy changes and clinical insomnia severity for CBT-I in patients with primary insomnia METHODS: Fifty-two outpatients (mean age, 60.3 years; 26 women) with primary insomnia were treated by individual CBT-I (50 min, maximum six sessions, once every 1-2 weeks). One week before and after CBT-I, patients recorded a sleep log and wore an actigraphy device. Subjective and objective time in bed (TIB), total sleep time (TST), sleep-onset latency (SOL), wake time after sleep onset (WASO), and sleep efficiency (SE) were evaluated by averaging 1-week records. Relative values of sleep discrepancy in TIB, TST, SOL, WASO, and SE were calculated for estimating effects of CBT-I. The therapeutic effects were also evaluated using psychological scales before and after CBT-I. RESULTS: Subjective and objective discrepancies in sleep measures decreased by 36, 25, and 37 min in TST, SOL, and WASO, respectively, and 7% in SE (all P < 0.001) after CBT-I. Seven patients transitioned from underestimating SE before CBT-I to overestimating SE after CBT-I. Although CBT-I improved relative values of discrepancy in WASO and SE, alongside ISI, the improvement in insomnia severity only correlated with SOL discrepancy. CONCLUSIONS: CBT-I may reduce the discrepancy between subjective and objective sleep measures in patients with primary insomnia. However, a greater therapeutic effect of CBT-I was observed in reducing the ISI, which was slightly influenced by improvements in sleep discrepancies.

Contribution of Somatosensory and Parietal Association Areas in Improving Standing Postural Stability Through Standing Plantar Perception Training in Community-Dwelling Older Adults.

Although standing plantar perception training (SPPT) may improve standing postural stability, the underlying neural mechanisms remain unclear. The authors investigated the relationship between regional cortical responses to SPPT using a balance pad and training outcomes in 32 older participants (mean ± SD:72.2 ± 6.0, range:60-87). Regional cortical activity was measured in the bilateral supplementary motor area, primary sensorimotor area, and parietal association area using near-infrared spectroscopy. Postural sway changes were compared before and after SPPT. Changes in two-point plantar discrimination and regional cortical activity during SPPT, associated with standing postural stability improvements, were examined using multiple regression and indicated improved standing postural stability after SPPT (p < .0001). Changes in right parietal association area activity were associated with standing postural stability improvements while barefoot. Overall, the results suggest that right parietal association area activation during SPPT plays a crucial role in regulating standing postural stability and may help develop strategies to prevent older adults from falling.

[Rapid Recurrence of Dedifferentiated Liposarcoma of Occult Primary in the Abdomen-A Case Report].

A man in his 70s was referred to our hospital for the examination of an abdominal tumor detected incidentally. The tumor was resected with a preoperative diagnosis of gastric submucosal tumor. As a result of the histopathological examination, dedifferentiated liposarcoma was diagnosed. The tumor recurred 2 months after the operation, and resection was attempted again. However, the intraoperative findings showed multiple metastatic lesions, and radical resection was considered impossible. Chemotherapy was therefore administered with doxorubicin monotherapy and eribulin, but the tumor rapidly increased, and the patient ultimately died 8 months after the initial operation. Dedifferentiated liposarcoma is a histologic type with a poor prognosis among liposarcoma. Resection is the standard treatment, but it frequently develops in the retroperitoneum, and it is often found in an advanced state due to the lack of subjective symptoms compared to lesions of the extremities. In addition, its tendency to infiltrate into the surrounding area and to metastasize are also factors that make radical resection difficult. We herein report a case of dedifferentiated liposarcoma that was detected asymptomatically but had a rapid outcome.

[Mastectomy Followed by Skin-Transplantation Restored QOL and Enabled Chemotherapy in Two Cases of Locally Advanced Breast Cancer with Uncontrollable Bleeding].

Here, we report 2 cases of locally advanced breast cancer with uncontrollable bleeding treated with mastectomy followed by skin transplantation. The operation restored the QOL and enabled chemotherapy in postoperative periods. Case 1: A woman in her 70s was brought by an ambulance because of heart failure symptoms. She had a huge breast tumor on her left chest wall that bled repeatedly, necessitating frequent blood transfusions. An operation was performed, and chemotherapy was provided until she died of brain metastasis 1 year and 8 months after surgery. Case 2: A woman in her 70s was urgently hospitalized with a lumbar vertebrae bone fracture. She had a huge breast tumor on her right chest wall that bled repeatedly. Blood examination revealed severe anemia. An operation was performed, and chemotherapy was introduced sequentially. She is alive with a good status 2 years and 1 month after surgery.

Loss of function at RAE2, a previously unidentified EPFL, is required for awnlessness in cultivated Asian rice.

Domestication of crops based on artificial selection has contributed numerous beneficial traits for agriculture. Wild characteristics such as red pericarp and seed shattering were lost in both Asian (Oryza sativa) and African (Oryza glaberrima) cultivated rice species as a result of human selection on common genes. Awnedness, in contrast, is a trait that has been lost in both cultivated species due to selection on different sets of genes. In a previous report, we revealed that at least three loci regulate awn development in rice; however, the molecular mechanism underlying awnlessness remains unknown. Here we isolate and characterize a previously unidentified EPIDERMAL PATTERNING FACTOR-LIKE (EPFL) family member named REGULATOR OF AWN ELONGATION 2 (RAE2) and identify one of its requisite processing enzymes, SUBTILISIN-LIKE PROTEASE 1 (SLP1). The RAE2 precursor is specifically cleaved by SLP1 in the rice spikelet, where the mature RAE2 peptide subsequently induces awn elongation. Analysis of RAE2 sequence diversity identified a highly variable GC-rich region harboring multiple independent mutations underlying protein-length variation that disrupt the function of the RAE2 protein and condition the awnless phenotype in Asian rice. Cultivated African rice, on the other hand, retained the functional RAE2 allele despite its awnless phenotype. Our findings illuminate the molecular function of RAE2 in awn development and shed light on the independent domestication histories of Asian and African cultivated rice.

High-resolution mapping of GRH6, a gene from Oryza nivara (Sharma et Shastry) conferring resistance to green rice leafhopper (Nephotettix cincticeps Uhler).

The green rice leafhopper (GRH), Nephotettix cincticeps Uhler, is a major insect pest of cultivated rice, Oryza sativa L., throughout the temperate regions of East Asia. GRH resistance had been reported in the wild species Oryza nivara but genetic basis of GRH resistance in wild rice accession has not been clarified. Here, we found a major QTL, qGRH4.2, on chromosome 4 conferred GRH resistance with 14.1 of the logarithm of odds (LOD) score explaining 67.6% of phenotypic variance in the BC1F1 population derived from a cross between the susceptible japonica cultivar 'Taichung 65' (T65) and O. nivara accession IRGC105715. qGRH4.2 has been identified as GRH6 between the markers RM5414 and C60248 in a BC3F2 population derived from two BC3F1 plants resistant to GRH. In a high-resolution mapping, the GRH6 region was delimited between the markers G6-c60k and 7L16f, and corresponded to an 31.2-kbp region of the 'Nipponbare' genome. Understanding the genetic basis of GRH resistance will facilitate the use of GRH resistance genes in marker-assisted breeding in rice.

Development of introgression lines of AA genome Oryza species, O. glaberrima, O. rufipogon, and O. nivara, in the genetic background of O. sativa L. cv. Taichung 65.

To evaluate and utilize potentially valuable quantitative trait loci or genes of wild relatives in the genetic background of domesticated crop species, chromosome segment substitution lines (CSSLs) are a valuable tool. CSSLs can be constructed through the exchange of chromosome segments of AA genome species of the genus Oryza with cultivated rice, Oryza sativa L. Here we report the development of three sets of CSSLs carrying segments of AA genome species closely related to Oryza sativa-O. glaberrima (IRGC 103777 from Mali), O. rufipogon (W1962 from China), and O. nivara (IRGC 105715 from Cambodia)-in the genetic background of ssp. japonica cultivar Taichung 65 through the use of 101 to 121 simple-sequence-repeat markers in whole-genome genotyping and marker-assisted selection. The materials are available via the National Bioresource Project (Rice) Oryzabase Web page.

[A Case of Gastrointestinal Perforation in Gastric Cancer during Chemotherapy with Paclitaxel plus Ramucirumab].

A 54-year-old man underwent distal gastrectomy with D2 lymph node dissection in our institution in March 2017 due to the presence of advanced gastric cancer. The pathological diagnosis was signet ring, poorly differentiated, and moderate differentiated adenocarcinoma, which was pT4aN3aM0, pStage Ⅲc and HER2-negative. After surgery, he received adjuvant chemotherapy with S-1, however, he was diagnosed with dissemination and lymph node recurrence in June. Tumor marker, CEA level decreased after the introduction of the next treatment(capecitabine plus cisplatin), however the tumor marker level rose again in September, and the chemotherapy regimen was changed to weekly paclitaxel(PTX). Furthermore, ramucirumab was added to the weekly PTX regime in January 2018, as the tumor marker level rose again. One week after the last ramucirumab administration he visited our hospital with abdominal pain, and emergency surgery was performed after the diagnosis of a gastrointestinal perforation using CT. The surgery revealed dirty fluid and countless dissemination nodes throughout the abdominal cavity, and a small intestinal perforation on a white dissemination node was identified 70 cm proximal to the end of the ileum. We performed small bowel segmental resection and functional end-to-end anastomosis. No complications were observed, and an oral diet was able to be started after surgery; however, he was introduced to the best supportive care(BSC)as his general condition gradually deteriorated.

[Curative Resection of Locally Advanced Rectal Cancer with Synchronous Liver Metastasis after Long-Term Chemotherapy].

A 60s man was diagnosed with unresectable advanced rectal cancer with synchronous solitary liver metastasis. Chemotherapy was administered and the primary tumor shrank immediately. However, he still demonstrated dorsal extension; therefore, chemotherapy was continued for approximately 1 year. After long-term chemotherapy, the primary tumor was deemed to be resectable because the dorsal extension had decreased. We achieved curative resection by performing a primary tumor and liver resection and he has shown no recurrence without adjuvant chemotherapy. Although the primary tumor was initially diagnosed as unresectable, it is important to consider the potential for curative resection after long-term chemotherapy.

Rice leaf hydrophobicity and gas films are conferred by a wax synthesis gene (LGF1) and contribute to flood tolerance.

Floods impede gas (O2 and CO2 ) exchange between plants and the environment. A mechanism to enhance plant gas exchange under water comprises gas films on hydrophobic leaves, but the genetic regulation of this mechanism is unknown. We used a rice mutant (dripping wet leaf 7, drp7) which does not retain gas films on leaves, and its wild-type (Kinmaze), in gene discovery for this trait. Gene complementation was tested in transgenic lines. Functional properties of leaves as related to gas film retention and underwater photosynthesis were evaluated. Leaf Gas Film 1 (LGF1) was identified as the gene determining leaf gas films. LGF1 regulates C30 primary alcohol synthesis, which is necessary for abundant epicuticular wax platelets, leaf hydrophobicity and gas films on submerged leaves. This trait enhanced underwater photosynthesis 8.2-fold and contributes to submergence tolerance. Gene function was verified by a complementation test of LGF1 expressed in the drp7 mutant background, which restored C30 primary alcohol synthesis, wax platelet abundance, leaf hydrophobicity, gas film retention, and underwater photosynthesis. The discovery of LGF1 provides an opportunity to better understand variation amongst rice genotypes for gas film retention ability and to target various alleles in breeding for improved submergence tolerance for yield stability in flood-prone areas.

Selection criteria for SNP loci to maximize robustness of high-resolution melting analysis for plant breeding.

DNA markers are useful for identifying genes and developing new genetic materials for breeding and genetic research. High-resolution melting (HRM) analysis can detect a single nucleotide polymorphism (SNP) in two polymerase chain reaction (PCR) fragments as a melting temperature (Tm) difference without additional experimental steps, such as gel electrophoresis. To design a method for developing reliable HRM markers that discriminate between homozygous alleles containing SNPs, we tested new evaluation indexes related to the thermodynamics of double-stranded DNA to find one that maximizes the difference in Tm values between PCR fragments. We found that differences in the change in Gibbs free energy (ΔG°) correlated with actual differences in Tm values. Optimization of the nearest neighboring nucleotide (NNN) of a SNP by nucleotide substitution in the primer and reducing the size of the PCR fragment both enlarged the actual differences in Tm. The genetic DNA markers we developed by NNN substitution, termed NNNs-HRM markers, could be precisely mapped within soybean chromosomes by linkage analysis. We developed a Perl script pipeline to enable the automatic design of a massive number of NNNs-HRM markers; these scripts are freely available and would be useful for practical breeding programs for other plant species.