Histone deacetylation regulates de novo shoot regeneration.

During de novo plant organ regeneration, auxin induction mediates the formation of a pluripotent cell mass called callus, which regenerates shoots upon cytokinin induction. However, molecular mechanisms underlying transdifferentiation remain unknown. Here, we showed that the loss of HDA19, a histone deacetylase (HDAC) family gene, suppresses shoot regeneration. Treatment with an HDAC inhibitor revealed that the activity of this gene is essential for shoot regeneration. Further, we identified target genes whose expression was regulated through HDA19-mediated histone deacetylation during shoot induction and found that ENHANCER OF SHOOT REGENERATION 1 and CUP-SHAPED COTYLEDON 2 play important roles in shoot apical meristem formation. Histones at the loci of these genes were hyperacetylated and markedly upregulated in hda19. Transient ESR1 or CUC2 overexpression impaired shoot regeneration, as observed in hda19. Therefore, HDA19 mediates direct histone deacetylation of CUC2 and ESR1 loci to prevent their overexpression at the early stages of shoot regeneration.

Multijurisdictional Outbreak of Enterohemorrhagic Escherichia coli O157 Caused by Consumption of Ready-to-Eat Grilled Skewered Meat in Niigata, Japan.

Enterohemorrhagic Escherichia coli O157 (EHEC) causes severe complications such as hemolytic uremic syndrome. Contaminated ready-to-eat (RTE) food is one of the vehicles of multijurisdictional outbreaks of foodborne disease worldwide. Multijurisdictional (covering cities, towns, and villages) outbreaks of EHEC are usually linked to an increase in cases, and here we describe such an outbreak involving 29 cases in October 2017 in the Niigata Prefecture. After prefecture-wide active case finding, we conducted a case-control study of 29 cases with eligible data who tested positive for EHEC. To determine the association of the outbreak with risk factors, we compared these cases with 38 controls selected from family and acquaintances who were both symptom free and tested negative for EHEC. The largest number of cases was in the 20-29-year age group (7/29; 24%) and most were women (20/29; 69%). All 29 cases had an identical or similar multilocus variable number tandem-repeat analysis (MLVA) profile. Of these, 76% (22/29) had consumed some type of grilled skewered meat. Also, 69% (20/29) had consumed grilled skewered meat produced by company X. EHEC infection was strongly associated with the consumption of grilled skewered meat produced by any food processing company (odds ratio [OR] = 11.8, confidence interval [95% CI]: 3.7-37.4) and by company X (OR = 9.8, 95% CI: 3.2-30.7). At company X, the skewered meat was grilled to 95°C and then removed from the grilling area to meat trays. The meat trays were not sufficiently washed and disinfected. Testing indicated that the facility was negative for EHEC but four asymptomatic employees tested positive for EHEC. Company X was temporarily closed and voluntarily recalled the foods. We recommend that all employees sufficiently wash and disinfect meat trays to prevent contamination of RTE food, avoid cross-contamination of grilled skewered meat through the environment by regularly cleaning the facility, and appropriately practice self-health care.

Genetic Characterization of Streptococcus pyogenes emm89 Strains Isolated in Japan From 2011 to 2019.

Invasive infection caused by Streptococcus pyogenes emm89 strains has been increasing in several countries linked to a recently emergent clade of emm89 strains, designated clade 3. In Japan, the features of emm89 S. pyogenes strains, such as clade classification, remains unknown. In this study, we collected emm89 strains isolated from both streptococcal toxic shock syndrome (STSS) (89 STSS isolates) and noninvasive infections (72 non-STSS isolates) in Japan from 2011 to 2019, and conducted whole-genome sequencing and comparative analysis, which resulted in classification of a large majority into clade 3 regardless of disease severity. In addition, invasive disease-associated factors were found among emm89 strains, including mutations of control of virulence sensor, and absence of the hylP1 gene encoding hyaluronidase. These findings provide new insights into genetic features of emm89 strains.

Effect of tumor necrosis factor-α antagonists on oxidative stress in patients with Crohn's disease.

AIM: To investigate changes in oxidative stress in Crohn's disease (CD) before and after anti-tumor necrosis factor (TNF)-α treatment. METHODS: A total of 42 patients with active CD, who were scheduled to be treated by anti-TNF-α antibodies, were enrolled. Serum levels of diacron-reactive oxygen metabolites (d-ROM), biological antioxidant potential (BAP), and modified ratio of oxidative stress and antioxidant capacity (m-OA) were measured using the Free Radical Analytical System before and 8 wk after induction of therapy with infliximab or adalimumab. The values for oxidative stress were correlated with disease activity and clinical response as determined by the CD activity index (CDAI) at 8 and 54 wk after the therapy. RESULTS: Prior to treatment, d-ROM showed significant correlations with CDAI (r = 0.42, P < 0.01). There was a significant negative correlation between m-OA and CDAI before and after treatment (r = -0.48 vs r = -0.42, P < 0.01). CDAI and d-ROM had decreased significantly by 8 wk after treatment (CDAI; 223.3 ± 113.2 vs 158.3 ± 73.4, P < 0.01, d-ROM; 373 ± 133 vs 312 ± 101, P < 0.05). However, neither BAP nor m-OA had changed significantly. In patients who had responded to the treatment at 8 wk, d-ROM, BAP, and m-OA levels before treatment did not differ significantly between patients with and without loss of response. CONCLUSION: Anti-TNF-α therapy decreases oxidative stress in patients with CD, but does not alter the production of antioxidants. Dysregulation of antioxidants may be associated with the disease.

Long-term efficacy and safety of ramosetron in the treatment of diarrhea-predominant irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a functional disease with persisting gastrointestinal symptoms that has been classified into four subtypes. Serotonin (5-hydroxytryptamine [5-HT]) plays important physiological roles in the contraction and relaxation of smooth muscle. Intraluminal distension of the intestine is known to stimulate the release of endogenous 5-HT from enterochromaffin cells, activating 5-HT3 receptors located on primary afferent neurons and leading to increases in intestinal secretions and peristaltic activity. Ramosetron, a potent and selective 5-HT3-receptor antagonist, has been in development for use in patients suffering from diarrhea-predominant IBS. In a double-blind, placebo-controlled, parallel-group study of 418 patients with diarrhea-predominant IBS-D, once-daily 5 µg and 10 µg doses of ramosetron increased the monthly responder rates of IBS symptoms compared to placebo. In a 12-week randomized controlled trial of 539 patients, a positive response to treatment was reported by 47% of a once-daily 5 µg dose of ramosetron-treated individuals compared to 27% of patients receiving placebo (P<0.001). Furthermore, the responder rate was increased in the oral administration of 5 µg of ramosetron for at least 28 weeks (up to 52 weeks), and long-term efficacy for overall improvement of IBS symptoms was also demonstrated. The rate was further increased subsequently. Adverse events were reported by 7% in ramosetron treatment. No serious adverse events, eg, severe constipation or ischemic colitis, were reported for long-term treatment with ramosetron. In conclusion, further studies to evaluate the long-term efficacy and safety of ramosetron are warranted in the form of randomized controlled trials.

Characteristics of caregiver perceptions of end-of-life caregiving experiences in cancer survivorship: in-depth interview study.

OBJECTIVE: Little is known about caregiver experiences during the end-of-life period. Our objective was to characterize caregiver perceptions of their experiences in cancer survivorship with special reference to the end-of-life stage considering depression in bereavement. METHODS: Qualitative research using in-depth interviews of 34 caregivers from two palliative care units in Japan. Data were analyzed inductively using framework analysis. Depression and personality traits were measured using the Center for Epidemiological Studies Depression (CES-D) and Sense of Coherence (SOC) scales, respectively. RESULTS: Caregiver perceptions were characterized along two axes. One axis involved four caregiver-cancer patient relationships: strengthening, reconstruction, intimacy-maintained, and estrangement-maintained. The core concept was transformation of relationships: caregivers reappraised aspects of caregiver-patient interactions through caregiving. The other axis involved subjective caregiving experiences divided into five concepts: spontaneity of care, discussing death, sympathy for patient emotions, impressions on first witnessing death, and introspective reflections in bereavement. Strengthening and reconstruction relationships appeared similar among the four relationship types, but only the former tended to overcompensate by sacrificing private time. Although median CES-D scores in each relationship type were under the cutoff for possible depression, four of eight caregivers suspected to have depressive tendencies belonged to the strengthening type. The mean SOC score for all caregivers was intermediate relative to scores previously reported in Japanese studies. CONCLUSIONS: While caregivers' subjective experiences can be classified, their relationship to depression in bereavement needs future research. The present findings indicate that caregivers should also be considered in clinicians' views of cancer survivorship.

Synthesis of five-, six-, and seven-membered ring lactams by CpRh complex-catalyzed oxidative N-heterocyclization of amino alcohols.

A new effective catalytic system consisting of [CpRhCl(2)](2)/K(2)CO(3) (Cp = pentamethylcyclopentadienyl) for the lactamization of amino alcohols has been developed. As an example, the reaction of 3-(2-aminophenyl)-1-propanol in the presence of [CpRhCl(2)](2) (5.0% Rh) and K(2)CO(3) (10%) in acetone gives 3,4-dihydro-2(1H)-quinolinone in an isolated yield of 80%. A variety of five-, six-, and seven-membered benzo-fused lactams are synthesized by this catalytic system. [reaction: see text]

Oxidative cyclization of amino alcohols catalyzed by a CpIr complex. Synthesis of indoles, 1,2,3,4-tetrahydroquinolines, and 2,3,4,5-tetrahydro-1-benzazepine.

[reaction: see text] A new iridium-catalyzed oxidative cyclization of amino alcohols has been revealed. Indole derivatives are synthesized in good to excellent yields from 2-aminophenethyl alcohols by means of a [CpIrCl(2)](2)/K(2)CO(3) catalytic system. The present catalytic system is also effective for syntheses of 1,2,3,4-tetrahydroquinolines from 3-(2-aminophenyl)propanols and 2,3,4,5-tetrahydro-1-benzazepine from 4-(2-aminophenyl)butanol.