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As an economic crop, pepper satisfies people's spicy taste and has medicinal uses worldwide. To gain a better understanding of Capsicum evolution, domestication, and specialization, we present here the genome sequence of the cultivated pepper Zunla-1 (C. annuum L.) and its wild progenitor Chiltepin (C. annuum var. glabriusculum). We estimate that the pepper genome expanded â¼0.3 Mya (with respect to the genome of other Solanaceae) by a rapid amplification of retrotransposons elements, resulting in a genome comprised of â¼81% repetitive sequences. Approximately 79% of 3.48-Gb scaffolds containing 34,476 protein-coding genes were anchored to chromosomes by a high-density genetic map. Comparison of cultivated and wild pepper genomes with 20 resequencing accessions revealed molecular footprints of artificial selection, providing us with a list of candidate domestication genes. We also found that dosage compensation effect of tandem duplication genes probably contributed to the pungent diversification in pepper. The Capsicum reference genome provides crucial information for the study of not only the evolution of the pepper genome but also, the Solanaceae family, and it will facilitate the establishment of more effective pepper breeding programs.
Assuntos
Capsicum/genética , Genoma de Planta , Elementos de DNA Transponíveis , Dados de Sequência Molecular , Proteínas de Plantas/genética , Retroelementos , Seleção Genética , Transcrição GênicaRESUMO
BACKGROUND: In this single-institution case-control study, we identified risk factors associated with inflammatory breast cancer (IBC) subtypes based on staining of estrogen receptor (ER), progesterone receptor (PR) and expression of human epidermal growth factor 2 (HER2neu) to determine distinct etiologic pathways. METHODS: We identified 224 women with IBC and 396 cancer-free women seen at the MD Anderson Cancer Center. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for associations between breast cancer risk factors and the IBC tumor subtypes: luminal (ER+ and/or PR+/HER2neu-), HER2neu+ (any ER and PR, HER2neu+), and triple-negative (ER-/PR-/HER2neu-). RESULTS: In multivariable analysis, compared with women age ≥26 at first pregnancy, women age <26 had a higher risk of triple-negative IBC (OR 3.32, 95% CI 1.37-8.05). Women with a history of breast-feeding had a lower risk of triple-negative (OR 0.30; 95% CI 0.15-0.62) and luminal IBC (OR 0.35, 95% CI 0.18-0.68). A history of smoking was associated with an increased risk of luminal IBC (OR 2.37; 95% CI 1.24-4.52). Compared with normal-weight women, those who were overweight or obese (body mass index ≥25 kg/m(2)) had a higher risk of all three tumor subtypes (p < 0.01 for all subtypes). CONCLUSION: Overweight or obese status is important modifiable risk factor for IBC of any subtype. Modifiable risk factors, age at first pregnancy (≥26), breast-feeding, and smoking may be associated with specific IBC subtypes. These results highlight the importance of evaluating epidemiologic risk factors for IBC for the identification of subtype-specific prevention strategies.
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Neoplasias Inflamatórias Mamárias/patologia , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Aleitamento Materno/estatística & dados numéricos , Estudos de Casos e Controles , Feminino , Humanos , Neoplasias Inflamatórias Mamárias/etiologia , Modelos Logísticos , Pessoa de Meia-Idade , Obesidade/epidemiologia , Gravidez , Receptor ErbB-2/metabolismo , Fatores de Risco , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/patologia , Adulto JovemRESUMO
Idecabtagene vicleucel (ide-cel), a B-cell maturation antigen-directed chimeric antigen receptor T cell therapy, showed deep, durable responses in patients with triple-class exposed, relapsed and refractory multiple myeloma (RRMM) in the phase 2 KarMMa (Efficacy and Safety Study of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma) trial. We assessed health-related quality of life (HRQoL) among KarMMa patients. The European Organization for Research and Treatment of Cancer Quality of Life C30 Questionnaire and its supplementary 20-item multiple myeloma module, as well as the EuroQol 5-dimension 5-level instrument, were administered at screening, baseline (≤72 hours before or same day as lymphodepletion), day of ide-cel treatment, and after ide-cel treatment. Mean changes from baseline that exceeded the predetermined threshold of minimally important difference were deemed clinically meaningful. The proportions of patients experiencing clinically meaningful changes in HRQoL were assessed using within-patient change thresholds. Time to stable improvement (≥2 consecutive visits with clinically meaningful HRQoL improvements) was analyzed by using the Kaplan-Meier method. A total of 126 (98%) of 128 patients treated with ide-cel were included in the HRQoL analysis. Pretreatment baseline RRMM burden was high and meaningfully worse than that in the age- and sex-weighted general population. Statistically significant and clinically meaningful improvements from baseline were observed by month 1 for pain (-8.9) and disease symptoms (-10.2), and by month 2 for fatigue (-7.2), physical functioning (6.1), cognitive functioning (6.7), and global health status/QoL (8.0). Clinically meaningful improvements in fatigue, pain, and physical functioning were most prominent at months 9, 12, and 18, respectively, and were sustained through 15 to 18 months after ide-cel treatment. For triple-class exposed patients with RRMM with a poor prognosis and few treatment options, a single ide-cel infusion provides early, sustained, statistically significant, and clinically meaningful improvements in HRQoL. This study was registered at Clinicaltrials.gov as #NCT03361748.
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Mieloma Múltiplo , Receptores de Antígenos Quiméricos , Fadiga , Humanos , Mieloma Múltiplo/terapia , Dor , Qualidade de Vida , Receptores de Antígenos Quiméricos/uso terapêuticoRESUMO
Myelofibrosis symptoms compromise health-related quality of life (HRQoL). Ruxolitinib can reduce myelofibrosis symptom severity, but many patients discontinue ruxolitinib due to loss of response or unacceptable toxicity. Fedratinib is an oral, selective JAK2 inhibitor approved in the United States for treatment of patients with intermediate-2 or high-risk myelofibrosis. The single-arm, phase II JAKARTA2 trial assessed fedratinib 400 mg/d (starting dose) in patients with myelofibrosis previously treated with ruxolitinib. Patient-reported changes in myelofibrosis symptom severity using the modified Myelofibrosis Symptom Assessment Form (MFSAF), and overall HRQoL and functional status using the EORTC QLQ-C30, were evaluated at each cycle. Clinically meaningful changes from baseline HRQoL scores were based on effect sizes. Ninety patients were MFSAF-evaluable. Myelofibrosis symptoms were mild-to-moderate at baseline. Patients showed statistically significant and clinically meaningful improvements in total symptom scores from baseline on the MFSAF at all post baseline visits through the end of cycle 6 (EOC6). Baseline global health status/QoL and functional domain scores on the EORTC QLQ-C30 were meaningfully worse than in the general population. At EOC6, 44% of patients reported clinically meaningful improvements in global health status/QoL, and 30%-53% of patients experienced clinically meaningful improvement in QLQ-C30 functional domains across post baseline timepoints. Over 80% of ongoing patients perceived fedratinib as beneficial on the Patient's Global Impression of Change questionnaire. Fedratinib effects were consistent among prognostically relevant patient subgroups. Patients with myelofibrosis previously treated with ruxolitinib experienced clinically meaningful improvements in myelofibrosis symptom burden, overall HRQoL, and functional status in the first 6 months of fedratinib treatment.
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Patients with myelodysplastic syndromes (MDS) often experience chronic anemia and long-term red blood cell transfusion dependence associated with significant burden on clinical and health-related quality of life (HRQoL) outcomes. In the MEDALIST trial (NCT02631070), luspatercept significantly reduced transfusion burden in patients with lower-risk MDS who had ring sideroblasts and were refractory to, intolerant to, or ineligible for prior treatment with erythropoiesis-stimulating agents. We evaluated the effect of luspatercept on HRQoL in patients enrolled in MEDALIST using the EORTC QLQ-C30 and the QOL-E questionnaire. Change in HRQoL was assessed every 6 weeks in patients receiving luspatercept with best supportive care (+ BSC) and placebo + BSC from baseline through week 25. No clinically meaningful within-group changes and between-group differences across all domains of the EORTC QLQ-C30 and QOL-E were observed. On one item of the QOL-E MDS-specific disturbances domain, patients treated with luspatercept reported marked improvements in their daily life owing to the reduced transfusion burden, relative to placebo. Taken together with previous reports of luspatercept + BSC reducing transfusion burden in patients from baseline through week 25 in MEDALIST, these results suggest luspatercept may offer a treatment option for patients that reduces transfusion burden while providing stability in HRQoL.
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Support for research involving children has a complicated history. Pediatricians and families have a unique opportunity to share perspectives about the relevance of pediatric clinical research. A national broadcast film on pediatric clinical research was developed to improve knowledge about and willingness to consider a clinical study. The film was delivered to a public audience employing a pre-post design comparing knowledge about clinical research before and after watching If Not for Me: Children and Clinical Studies. Change was measured by the difference in number of questions answered correctly prior to and after viewing the film. Engagement was measured by survey and a live feedback qualitative component. Adults viewing the program demonstrated a significant (P < .0001) difference in knowledge about pediatric clinical research across all domains. This format appears to be a viable approach for improving public education and as a support tool for pediatricians and pediatric researchers about this topic.
Assuntos
Estudos Clínicos como Assunto/psicologia , Comunicação em Saúde/métodos , Filmes Cinematográficos , Pediatria , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
To investigate how high light affects the responses of photosynthesis to heat stress, the effects of high temperature (25-42.5 degrees C) either in the dark or in the light (1000 micromol m(-2) s(-1)) on photosystem II (PSII) photochemistry and the xanthophyll cycle were investigated in rice plants. At temperatures higher than 35 degrees C, there was a decrease in the CO(2) assimilation rate, and this decrease was greater in the light than in the dark. The maximal efficiency of PSII photochemistry (F(v)/F(m)) showed no significant change in the dark, but did show a significant decrease in the light. In addition, there was an increase in non-photochemical quenching (NPQ) and this increase was greater in the light than in the dark. Furthermore, the de-epoxidation status of the xanthophyll cycle increased significantly with increasing temperature in the light. Compared to the control leaves, the dithiothreitol-fed leaves showed a greater decrease in F(v)/F(m) but a very small increase in NPQ and de-epoxidation status of the xanthophyll cycle at temperatures higher than 35 degrees C. On the other hand, the ascorbate-fed leaves showed less of a decrease in F(v)/F(m) but a greater increase in NPQ and the de-epoxidation status of the xanthophyll cycle. Ascorbate peroxidase and glutathione reductase activities in leaves and chloroplasts were enhanced and this enhancement was greater in the light than in the dark. Heat stress had no significant effect on the contents of ascorbate and glutathione in leaves and chloroplasts in the dark, but led to an increase in the contents of reduced ascorbate and glutathione in leaves and chloroplasts in the light at the temperatures higher than 35 degrees C. Our results suggest that the xanthophyll cycle plays an important role in protecting PSII against heat-induced photoinhibition by an increase in the ascorbate pool in the chloroplast.