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1.
Proc Natl Acad Sci U S A ; 119(26): e2121692119, 2022 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-35733263

RESUMO

Asian rice (Oryza sativa L.) is consumed by more than half of the world's population. Despite its global importance, the process of early rice domestication remains unclear. During domestication, wild rice (Oryza rufipogon Griff.) acquired non-seed-shattering behavior, allowing humans to increase grain yield. Previous studies argued that a reduction in seed shattering triggered by the sh4 mutation led to increased yield during rice domestication, but our experiments using wild introgression lines show that the domesticated sh4 allele alone is insufficient for shattering loss in O. rufipogon. The interruption of abscission layer formation requires both sh4 and qSH3 mutations, demonstrating that the selection of shattering loss in wild rice was not as simple as previously suggested. Here we identified a causal single-nucleotide polymorphism at qSH3 within the seed-shattering gene OsSh1, which is conserved in indica and japonica subspecies but absent in the circum-aus group of rice. Through harvest experiments, we further demonstrated that seed shattering alone did not significantly impact yield; rather, yield increases were observed with closed panicle formation controlled by SPR3 and further augmented by nonshattering, conferred by integration of sh4 and qSH3 alleles. Complementary manipulation of panicle shape and seed shattering results in a mechanically stable panicle structure. We propose a stepwise route for the earliest phase of rice domestication, wherein selection of visible SPR3-controlled closed panicle morphology was instrumental in the sequential recruitment of sh4 and qSH3, which together led to the loss of shattering.


Assuntos
Domesticação , Genes de Plantas , Oryza , Dispersão de Sementes , Sementes , Alelos , Humanos , Mutação , Oryza/genética , Oryza/fisiologia , Fenótipo , Polimorfismo de Nucleotídeo Único , Dispersão de Sementes/genética , Sementes/genética , Sementes/fisiologia
2.
J Biol Chem ; 299(5): 104691, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37037306

RESUMO

Mitophagy is a cargo-specific autophagic process that recycles damaged mitochondria to promote mitochondrial turnover. PTEN-induced putative kinase 1 (PINK1) mediates the canonical mitophagic pathway. However, the role of PINK1 in diseases where mitophagy has been purported to play a role, such as colorectal cancer, is unclear. Our results here demonstrate that higher PINK1 expression is positively correlated with decreased colon cancer survival, and mitophagy is required for colon cancer growth. We show that doxycycline-inducible knockdown (KD) of PINK1 in a panel of colon cancer cell lines inhibited proliferation, whereas disruption of other mitophagy receptors did not impact cell growth. We observed that PINK KD led to a decrease in mitochondrial respiration, membrane hyperpolarization, accumulation of mitochondrial DNA, and depletion of antioxidant glutathione. In addition, mitochondria are important hubs for the utilization of iron and synthesizing iron-dependent cofactors such as heme and iron sulfur clusters. We observed an increase in the iron storage protein ferritin and a decreased labile iron pool in the PINK1 KD cells, but total cellular iron or markers of iron starvation/overload were not affected. Finally, cellular iron storage and the labile iron pool are maintained via autophagic degradation of ferritin (ferritinophagy). We found overexpressing nuclear receptor coactivator 4, a key adaptor for ferritinophagy, rescued cell growth and the labile iron pool in PINK1 KD cells. These results indicate that PINK1 integrates mitophagy and ferritinophagy to regulate intracellular iron availability and is essential for maintaining intracellular iron homeostasis to support survival and growth in colorectal cancer cells.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Mitofagia , Proteínas Quinases , Humanos , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Ferritinas , Ferro/metabolismo , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
3.
Am J Physiol Gastrointest Liver Physiol ; 326(1): G53-G66, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37933447

RESUMO

Neutrophils are abundant immune cells in the colon tumor microenvironment. Studies have shown that neutrophils are recruited into hypoxic foci in colon cancer. However, the impact of hypoxia signaling on neutrophil function and its involvement in colon tumorigenesis remain unclear. To address this, we generated mice with a deletion of hypoxia-inducible factor (HIF)-1α or HIF-2α in neutrophils driven by the MRP8Cre (HIF-1αΔNeu) or (HIF-2αΔNeu) and littermate controls. In an azoxymethane (AOM)/dextran sulfate sodium (DSS) model of colon cancer, the disruption of neutrophils-HIF-1α did not result in any significant changes in body weight, colon length, tumor size, proliferation, or burden. However, the disruption of HIF-2α in neutrophils led to a slight increase in body weight, a significant decrease in the number of tumors, and a reduction in tumor size and volume compared with their littermate controls. Histological analysis of colon tissue from mice with HIF-2α-deficient neutrophils revealed notable reductions in proliferation as compared with control mice. In addition, we observed reduced levels of proinflammatory cytokines, such as TNF-α and IL-1ß, in neutrophil-specific HIF-2α-deficient mice in both the tumor tissue as well as the neutrophils. Importantly, it is worth noting that the reduced tumorigenesis associated with HIF-2α deficiency in neutrophils was not evident in already established syngeneic tumors or a DSS-induced inflammation model, indicating a potential role of HIF-2α specifically in colon tumorigenesis. In conclusion, we found that the loss of neutrophil-specific HIF-2α slows colon tumor growth and progression by reducing the levels of inflammatory mediators.NEW & NOTEWORTHY Despite the importance of hypoxia and neutrophils in colorectal cancer (CRC), the contribution of neutrophil-specific HIFs to colon tumorigenesis is not known. We describe that neutrophil HIF-1α has no impact on colon cancer, whereas neutrophil HIF-2α loss reduces CRC growth by decreasing proinflammatory and immunosuppressive cytokines. Furthermore, neutrophil HIF-2α does not reduce preestablished tumor growth or inflammation-induced colitis. The present study offers novel potential of neutrophil HIF-2α as a therapeutic target in CRC.


Assuntos
Neoplasias Associadas a Colite , Neoplasias do Colo , Animais , Camundongos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Peso Corporal , Carcinogênese/patologia , Transformação Celular Neoplásica/patologia , Neoplasias Associadas a Colite/genética , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Citocinas , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Inflamação , Neutrófilos , Microambiente Tumoral
4.
Proc Natl Acad Sci U S A ; 118(47)2021 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-34751161

RESUMO

When the first rice farmers expanded into Southeast Asia from the north about 4,000 y ago, they interacted with hunter-gatherer communities with an ancestry in the region of at least 50 millennia. Rigorously dated prehistoric sites in the upper Mun Valley of Northeast Thailand have revealed a 12-phase sequence beginning with the first farmers followed by the adoption of bronze and then iron metallurgy leading on to the rise of early states. On the basis of the burial rituals involving interment with a wide range of mortuary offerings and associated practices, we identify, by computing the values of the Gini coefficient, at least two periods of intensified social inequality. The first occurred during the initial Bronze Age that, we suggest, reflected restricted elite ownership of exotic valuables within an exchange choke point. The second occurred during the later Iron Age when increased aridity stimulated an agricultural revolution that rapidly led to the first state societies in mainland Southeast Asia.

5.
Reprod Domest Anim ; 59(5): e14578, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38715446

RESUMO

To the best of the authors' knowledge, no study has previously investigated whether the concentration of minerals is related to reproductive outcomes in primiparous cows. For this reason, two objectives were set in the present study: (i) to assess serum mineral levels, macrominerals, and trace elements during the transition period (period of high nutritional requirements) in primiparous cows, considering reproductive efficiency, and (ii) to address if the serum mineral levels of primiparous cows are related to reproductive efficiency. Blood samples were taken (i) one month before calving, (ii) one week before calving, (iii) one week postpartum, and (iv) one month postpartum. At the beginning and the end of the study, a body condition score (BCS) was assigned to each lactating cow with no clinical signs of disease. The difference between one month before and one month after calving was the body condition loss (ΔBCS). Optimal prepartum concentrations of K and Cl were associated with fewer days open and a shorter interval calving. Furthermore, macrominerals in the serum decreased immediately after calving (one week) but recovered at one month postpartum. In contrast, the highest concentration of trace elements was found at one week postpartum. Primiparous cows with higher postpartum Se, Mn, Co, and Mo concentrations exhibited better reproductive efficiency, and the concentrations of trace elements in serum were correlated with interval calving and the number of inseminations. Finally, primiparous cows with a greater ΔBCS (at least one point) in period 4 exhibited both a longer calving interval and a greater number of days open. In summary, this study showed, for the first time in primiparous cows, that the concentration of some serum minerals not only plays a crucial role during the transition period but is also related to crucial reproductive parameters, such as interval calving and days open.


Assuntos
Lactação , Minerais , Paridade , Período Periparto , Reprodução , Animais , Feminino , Bovinos/fisiologia , Bovinos/sangue , Período Periparto/sangue , Gravidez , Minerais/sangue , Reprodução/fisiologia , Lactação/fisiologia , Oligoelementos/sangue , Período Pós-Parto/sangue
6.
Rev Esp Enferm Dig ; 115(12): 750-751, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37539537

RESUMO

Melanoma is a cancer that frequently metastasises to the small bowel, but most cases are asymptomatic and are diagnosed postmortem. Therefore, CT and PET CT cannot detect all lesions and conventional endoscopic study only detects 10-20% of lesions. In this study, we present the case of a 68-year-old patient with a history of cutaneous melanoma and a diagnosis of intestinal melanoma. Thanks to capsule endoscopy, two lesions compatible with cutaneous melanoma metastasis to the small bowel were detected, allowing a much more effective surgical planning. Capsule endoscopy is an innovative technique that improves preoperative diagnosis, as it is able to detect bowel segments that cannot be inspected by conventional endoscopy. It also has a better resolution than conventional CT, improving sensitivity in the detection of lesions.


Assuntos
Endoscopia por Cápsula , Neoplasias Intestinais , Melanoma , Neoplasias Cutâneas , Humanos , Idoso , Melanoma/diagnóstico por imagem , Melanoma/patologia , Endoscopia por Cápsula/métodos , Neoplasias Cutâneas/patologia , Endoscopia Gastrointestinal , Intestino Delgado/patologia , Neoplasias Intestinais/diagnóstico por imagem , Neoplasias Intestinais/cirurgia , Hemorragia Gastrointestinal/patologia
7.
Medicina (Kaunas) ; 59(9)2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37763746

RESUMO

Anaplastic large cell lymphoma (ALCL) with leukaemic presentation (either ab initio or along the course of the disease) has been rarely reported. Irrespective of ALK expression in the neoplastic cells, it features a dismal prognosis. We report a rare case of leukaemic, small cell variant ALK-positive ALCL with 9-year survival in a young woman who was treated upfront with corticosteroids and standard chemotherapy, and review thoroughly the previously published cases. Such an unexpected, good outcome hints at the existence of different clinical subgroups in the leukaemic variant of ALK-positive ALCL.


Assuntos
Linfoma Anaplásico de Células Grandes , Feminino , Humanos , Linfoma Anaplásico de Células Grandes/diagnóstico , Linfoma Anaplásico de Células Grandes/tratamento farmacológico , Linfoma Anaplásico de Células Grandes/metabolismo , Quinase do Linfoma Anaplásico , Receptores Proteína Tirosina Quinases/uso terapêutico , Prognóstico
8.
Mol Biol Evol ; 38(11): 4832-4846, 2021 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-34240169

RESUMO

The dispersal of rice (Oryza sativa) following domestication influenced massive social and cultural changes across South, East, and Southeast (SE) Asia. The history of dispersal across islands of SE Asia, and the role of Taiwan and the Austronesian expansion in this process remain largely unresolved. Here, we reconstructed the routes of dispersal of O. sativa ssp. japonica rice to Taiwan and the northern Philippines using whole-genome resequencing of indigenous rice landraces coupled with archaeological and paleoclimate data. Our results indicate that japonica rice found in the northern Philippines diverged from Indonesian landraces as early as 3,500 years before present (BP). In contrast, rice cultivated by the indigenous peoples of the Taiwanese mountains has complex origins. It comprises two distinct populations, each best explained as a result of admixture between temperate japonica that presumably came from northeast Asia, and tropical japonica from the northern Philippines and mainland SE Asia, respectively. We find that the temperate japonica component of these indigenous Taiwan populations diverged from northeast Asia subpopulations at about 2,600 BP, whereas gene flow from the northern Philippines had begun before ∼1,300 BP. This coincides with a period of intensified trade established across the South China Sea. Finally, we find evidence for positive selection acting on distinct genomic regions in different rice subpopulations, indicating local adaptation associated with the spread of japonica rice.


Assuntos
Oryza , Sudeste Asiático , Domesticação , Fluxo Gênico , Oryza/genética , Taiwan
9.
Medicina (Kaunas) ; 58(4)2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35454359

RESUMO

BACKGROUND: The majority of patients with acute promyelocytic leukemia (APL) manifest a specific chromosomal translocation t(15;17)(q22;q21), characterized by the fusion of RARA and PML genes. However, a proportion of APL cases are due to variant translocations, being t(11;17) (q23;q21) the most common amongst them. With the major exception of ZBTB16-RARA t(11;17) APL, these variant APL cases present similar morphological features as classic APL and are characterized by a lack of differentiation response to retinoids. CASE SUMMARY: We describe the case of variant APL with the ZBTB16-RARA fusion gene, showing a distinct morphology of classical APL, characterized by crystalline intracytoplasmic inclusions in both peripheral blood (PB) and bone marrow (BM) patients' blasts. Our patient was treated with two courses of intensive chemotherapy, initiating maintenance treatment with all-trans retinoic acid (ATRA) on day twenty-eight of the second course. Our patient achieved complete remission (CR) once the intensive chemotherapy was combined with ATRA. CONCLUSIONS: This is the second case described of APL with t(11;17) that showed crystalline intracytoplasmic inclusions. The finding of these morphological features may suggest the presence of a variant translocation with RARA, being that both cases described are related to the presence of t(11;17). Despite induction treatment with intensive chemotherapy that included a seven-day continuous treatment with cytarabine (200 mg/m2), plus daily idarubicin (12 mg/m2) during the first three days, our patient did not achieve complete remission (CR) until scheduled 3 + 7 regimen combined with ATRA treatment was established. This observation suggests that ATRA may be partially effective in some ZBTB16-RARA APLs.


Assuntos
Leucemia Promielocítica Aguda , Medula Óssea , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/genética , Proteínas de Fusão Oncogênica/genética , Proteína com Dedos de Zinco da Leucemia Promielocítica/genética , Translocação Genética/genética , Tretinoína/uso terapêutico
10.
Aust Crit Care ; 35(1): 22-27, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34462194

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) has again highlighted the crucial role of healthcare workers in case management, disease surveillance, policy development, and healthcare education and training. The ongoing pandemic demonstrates the importance of having an emergency response plan that accounts for the safety of frontline healthcare workers, including those working in critical care settings. OBJECTIVES: The aim of the study was to explore Australian critical care nurses' knowledge, preparedness, and experiences of managing patients diagnosed with severe acute respiratory syndrome coronavirus 2 infection (SARS-CoV-2) and COVID-19. METHODS: An exploratory cross-sectional study of Australian critical care nurses was conducted between June and September 2020. An anonymised online survey was sent to Australian College of Critical Care Nurses' members to collect information about their knowledge, preparedness, and experiences during the COVID-19 pandemic. Descriptive statistics were used to summarise and report data. RESULTS: A total of 157 critical care nurses participated, with 138 fully complete surveys analysed. Most respondents reported 'good' to 'very good' level of knowledge about COVID-19 and obtained up-to-date COVID-19 information from international and local sources. Regarding managing patients with COVID-19, 82.3% felt sufficiently prepared at the time of data collection, and 93.4% had received specific education, training, or instruction. Most participants were involved in assessing (89.3%) and treating (92.4%) patients with COVID-19. Varying levels of concerns about SARS-CoV-2 infection were expressed by respondents, and 55.7% thought the pandemic had increased their workload. The most frequent concerns expressed by participants were a lack of appropriate personal protective equipment (PPE) and fear of PPE shortage. CONCLUSIONS: While most nurses expressed sufficient preparedness for managing COVID-19 patients, specific education had been undertaken and experiential learning was evident. Fears of insufficient or lack of appropriate PPE made the response more difficult for nurses and the community. Preparedness and responsiveness are critical to successful management of the COVID-19 pandemic and future outbreaks of emerging infectious diseases.


Assuntos
COVID-19 , Enfermeiras e Enfermeiros , Austrália , Competência Clínica , Cuidados Críticos , Estudos Transversais , Humanos , Pandemias , SARS-CoV-2
11.
Rev Environ Contam Toxicol ; 257: 163-218, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34487249

RESUMO

Plastic litter dispersed in the different environmental compartments represents one of the most concerning problems associated with human activities. Specifically, plastic particles in the micro and nano size scale are ubiquitous and represent a threat to human health and the environment. In the last few decades, a huge amount of research has been devoted to evaluate several aspects of micro/nano-plastic contamination: origin and emissions, presence in different compartments, environmental fate, effects on human health and the environment, transfer in the food web and the role of associated chemicals and microorganisms. Nevertheless, despite the bulk of information produced, several knowledge gaps still exist. The objective of this paper is to highlight the most important of these knowledge gaps and to provide suggestions for the main research needs required to describe and understand the most controversial points to better orient the research efforts for the near future. Some of the major issues that need further efforts to improve our knowledge on the exposure, effects and risk of micro/nano-plastics are: harmonization of sampling procedures; development of more accurate, less expensive and less time-consuming analytical methods; assessment of degradation patterns and environmental fate of fragments; evaluating the capabilities for bioaccumulation and transfer to the food web; and evaluating the fate and the impact of chemicals and microorganisms associated with micro/nano-plastics. The major gaps in all sectors of our knowledge, from exposure to potentially harmful effects, refer to small size microplastics and, particularly, to the occurrence, fate and effects of nanoplastics.


Assuntos
Plásticos , Poluentes Químicos da Água , Monitoramento Ambiental , Humanos , Microplásticos , Plásticos/toxicidade , Pesquisa , Poluentes Químicos da Água/análise
12.
Intern Med J ; 51(1): 42-51, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33196128

RESUMO

BACKGROUND: On 31 December 2019, the World Health Organization recognised clusters of pneumonia-like cases due to a novel coronavirus disease (COVID-19). COVID-19 became a pandemic 71 days later. AIM: To report the clinical and epidemiological features, laboratory data and outcomes of the first group of 11 returned travellers with COVID-19 in Australia. METHODS: This is a retrospective, multi-centre case series. All patients with confirmed COVID-19 infection were admitted to tertiary referral hospitals in New South Wales, Queensland, Victoria and South Australia. RESULTS: The median age of the patient cohort was 42 years (interquartile range (IQR), 24-53 years) with six men and five women. Eight (72.7%) patients had returned from Wuhan, one from Shenzhen, one from Japan and one from Europe. Possible human-to-human transmission from close family contacts in gatherings overseas occurred in two cases. Symptoms on admission were fever, cough and sore throat (n = 9, 81.8%). Co-morbidities included hypertension (n = 3, 27.3%) and hypercholesterolaemia (n = 2, 18.2%). No patients developed severe acute respiratory distress nor required intensive care unit admission or mechanical ventilation. After a median hospital stay of 14.5 days (IQR, 6.75-21), all patients were discharged. CONCLUSIONS: This is a historical record of the first COVID-19 cases in Australia during the early biocontainment phase of the national response. These findings were invaluable for establishing early inpatient and outpatient COVID-19 models of care and informing the management of COVID-19 over time as the outbreak evolved. Future research should extend this Australian case series to examine global epidemiological variation of this novel infection.


Assuntos
COVID-19/epidemiologia , Adulto , Austrália/epidemiologia , COVID-19/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Estudos Retrospectivos , Centros de Atenção Terciária , Adulto Jovem
13.
BMC Pulm Med ; 21(1): 271, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34418988

RESUMO

INTRODUCTION: Within the pathogenesis of the chronic obstructive pulmonary disease (COPD) there are interactions between different inflammatory mediators that are enhanced during an exacerbation. Arginase is present in bronchial epithelial cells, endothelial, fibroblasts and alveolar macrophages, which make it a probable key enzyme in the regulation of inflammation and remodelling. We aimed to find a potential relationship between arginase activity, inflammatory mediators in COPD patients in stable phase and during exacerbations. METHODS: We performed a prospective, observational study of cases and controls, with 4 study groups (healthy controls, stable COPD, COPD during an exacerbation and COPD 3 months after exacerbation). We measured arginase, inflammation markers (IL-6, IL-8, TNF-∝, IFN-γ and C reactive protein), and mediators of immunity: neutrophils, monocytes, total TCD3 + lymphocytes (CD3ζ), CD4 + T cells, CD8 + T cells, NK cells. RESULTS: A total of 49 subjects were recruited, average age of 69.73 years (59.18% male). Arginase activity is elevated during an exacerbation of COPD, and this rise is related to an increase in IL-6 production. The levels of IL-6 and IL-8 remained elevated in patients with COPD at 3 months after hospital exacerbation. We did not find a clear relationship between arginase activity, immunity or with the degree of obstruction in COPD patients. CONCLUSIONS: Arginase activity is elevated during an exacerbation of COPD, and it could be related to an increase in the production of IL-6. Levels of IL-6, IL-8, and arginase activity remain elevated in patients with COPD at 3 months after hospital exacerbation. Arginase activity could contribute to the development of COPD.


Assuntos
Arginase/metabolismo , Inflamação/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/fisiopatologia
14.
J Biol Chem ; 294(11): 3974-3986, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30659096

RESUMO

Hypoxia-inducible factor 2α (HIF2α) directly regulates a battery of genes essential for intestinal iron absorption. Interestingly, iron deficiency and overload disorders do not result in increased intestinal expression of glycolytic or angiogenic HIF2α target genes. Similarly, inflammatory and tumor foci can induce a distinct subset of HIF2α target genes in vivo These observations indicate that different stimuli activate distinct subsets of HIF2α target genes via mechanisms that remain unclear. Here, we conducted a high-throughput siRNA-based screen to identify genes that regulate HIF2α's transcriptional activity on the promoter of the iron transporter gene divalent metal transporter-1 (DMT1). SMAD family member 3 (SMAD3) and SMAD4 were identified as potential transcriptional repressors. Further analysis revealed that SMAD4 signaling selectively represses iron-absorptive gene promoters but not the inflammatory or glycolytic HIF2α or HIF1α target genes. Moreover, the highly homologous SMAD2 did not alter HIF2α transcriptional activity. During iron deficiency, SMAD3 and SMAD4 expression was significantly decreased via proteasomal degradation, allowing for derepression of iron target genes. Several iron-regulatory genes contain a SMAD-binding element (SBE) in their proximal promoters; however, mutation of the putative SBE on the DMT1 promoter did not alter the repressive function of SMAD3 or SMAD4. Importantly, the transcription factor forkhead box protein A1 (FOXA1) was critical in SMAD4-induced DMT1 repression, and DNA binding of SMAD4 was essential for the repression of HIF2α activity, suggesting an indirect repressive mechanism through DNA binding. These results provide mechanistic clues to how HIF signaling can be regulated by different cellular cues.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proteínas Reguladoras de Ferro/metabolismo , Proteína Smad3/metabolismo , Proteína Smad4/metabolismo , Animais , Células Cultivadas , Humanos , Proteínas Reguladoras de Ferro/genética , Camundongos , Camundongos Knockout , Proteína Smad3/deficiência , Proteína Smad4/deficiência
15.
Ann Bot ; 125(4): 581-597, 2020 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-31903489

RESUMO

BACKGROUND: Vegetatively propagated crops are globally significant in terms of current agricultural production, as well as for understanding the long-term history of early agriculture and plant domestication. Today, significant field crops include sugarcane (Saccharum officinarum), potato (Solanum tuberosum), manioc (Manihot esculenta), bananas and plantains (Musa cvs), sweet potato (Ipomoea batatas), yams (Dioscorea spp.) and taro (Colocasia esculenta). In comparison with sexually reproduced crops, especially cereals and legumes, the domestication syndrome in vegetatively propagated field crops is poorly defined. AIMS AND SCOPE: Here, a range of phenotypic traits potentially comprising a syndrome associated with early domestication of vegetatively propagated field crops is proposed, including: mode of reproduction, yield of edible portion, ease of harvesting, defensive adaptations, timing of production and plant architecture. The archaeobotanical visibility of these syndrome traits is considered with a view to the reconstruction of the geographical and historical pathways of domestication for vegetatively propagated field crops in the past. CONCLUSIONS: Although convergent phenotypic traits are identified, none of them are ubiquitous and some are divergent. In contrast to cereals and legumes, several traits seem to represent varying degrees of plastic response to growth environment and practices of cultivation, as opposed to solely morphogenetic 'fixation'.


Assuntos
Domesticação , Manihot , Agricultura , Produtos Agrícolas , Grão Comestível
16.
Theor Appl Genet ; 132(9): 2615-2623, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31222437

RESUMO

KEY MESSAGE: A novel locus, qCSS3, involved in the non-seed-shattering behaviour of Japonica rice cultivar, 'Nipponbare', was detected by QTL-seq analysis using the segregating population with the fixed known seed-shattering loci. Asian cultivated rice, Oryzasativa, was domesticated from its wild ancestor, O.rufipogon. Loss of seed shattering is one of the most recognisable traits selected during rice domestication. Three quantitative trait loci (QTLs), qSH1, qSH3, and sh4, were previously reported to be involved in the loss of seed shattering of Japonica cultivated rice, O.sativa 'Nipponbare'. However, the introgression line (IL) carrying 'Nipponbare' alleles at these three loci in the genetic background of wild rice, O.rufipogon W630, showed a lower value for detaching a grain from the pedicel than 'Nipponbare'. Here, we investigated abscission layer formation in the IL and found a partially formed abscission layer in the central region between the epidermis and vascular bundles. Based on QTL-seq analysis using the F2 population obtained from a cross between 'Nipponbare' and the IL, we detected two novel loci qCSS3 and qCSS9 (QTL for the Control of Seed Shattering in rice on chromosomes 3 and 9), which were found to be involved in the difference in seed-shattering degree between 'Nipponbare' and W630. Then, we further focused on qCSS3 in order to understand its potential role on the loss of seed shattering. The candidate region of qCSS3 was found to be located within a 526-kb region using substitution mapping analysis. Interestingly, the qCSS3 candidate region partially overlaps the selective sweep detected for Japonica but not for Indica rice cultivars, suggesting that this region harbours the mutation at a novel seed-shattering locus specifically selected for non-seed-shattering behaviour in Japonica cultivars.


Assuntos
Mapeamento Cromossômico/métodos , Cromossomos de Plantas/genética , Oryza/genética , Proteínas de Plantas/genética , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Sementes/genética , Genótipo , Oryza/crescimento & desenvolvimento , Fenótipo , Sementes/crescimento & desenvolvimento
17.
Eur J Clin Microbiol Infect Dis ; 38(4): 667-673, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30820840

RESUMO

The role of viral load in the outcome of patients requiring hospital admission due to influenza is not well established. We aim to assess if there is an association between the viral load and the outcome in hospitalized patients with a confirmed influenza virus infection. A retrospective observational study including all adult patients who were hospitalized in our center with a confirmed influenza virus infection from January to May 2016. Viral load was measured by real-time reverse-transcriptase-polymerase chain reaction (rRT-PCR) cycle threshold (Ct) value on upper respiratory tract samples. Its value was categorized into three groups (low Ct, ≤ 20; intermediate Ct, > 20-30; and high Ct, > 30). Two hundred thirty-nine patients were included. Influenza A/H1N1pdm09 was isolated in 207 cases (86.6%). The mean Ct value was 26.69 ± 5.81. The viral load was higher in the unvaccinated group when compared with the vaccinated patients (Ct 25.17 ± 5.55 vs. 27.58 ± 4.97, p = 0.004). Only 27 patients (11.29%) presented a high viral load. Patients with a high viral load more often showed abnormal findings on chest X-ray (p = 0.015) and lymphopenia (p = 0.097). By contrast, there were no differences between the three groups (according to viral load), in associated pneumonia, respiratory failure, need for mechanical ventilation, sepsis, or in-hospital mortality. Our findings suggest that in patients admitted to the hospital with confirmed influenza virus infection (mostly A/H1N1pdm09), a high viral load is associated with a higher presence of abnormal findings on chest X-ray but not with a significant worse prognosis. In these cases, standardized quantitative PCR could be useful.


Assuntos
Influenza Humana/diagnóstico , Carga Viral , Idoso , Idoso de 80 Anos ou mais , Doenças Transmissíveis , Feminino , Hospitalização , Humanos , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/complicações , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/mortalidade , Prognóstico , Radiografia , Reação em Cadeia da Polimerase em Tempo Real , Insuficiência Respiratória/virologia , Estudos Retrospectivos , Tórax/diagnóstico por imagem , Tórax/virologia , Vacinação/estatística & dados numéricos
18.
Proc Natl Acad Sci U S A ; 113(38): 10497-502, 2016 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-27582464

RESUMO

The inventories of carbon residing in organic matter dissolved in the ocean [dissolved organic carbon (DOC)] and in the atmosphere as CO2 are of the same order of magnitude, such that small changes in the DOC pool could have important consequences in atmospheric carbon and thus climate. DOC in the global ocean is largely formed in the sunlit euphotic zone, but identifying predictable controls on that production is an important yet unrealized goal. Here, we use a testable and causative correlation between the net production of DOC and the consumption of new nutrients in the euphotic zone of the Atlantic Ocean. We demonstrate that new nutrients introduced to the euphotic zone by upwelling in divergence zones and by winter convective overturn of the water column, and the primary production associated with those nutrients, are the ultimate driver of DOC distributions across the Atlantic basins. As new nutrient input will change with a changing climate, the role of DOC in the ocean's biological pump should likewise be impacted.

19.
Foodborne Pathog Dis ; 15(3): 161-167, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29336594

RESUMO

In Australia, the incidence of Salmonella Typhimurium has increased dramatically over the past decade. Whole-genome sequencing (WGS) is transforming public health microbiology, but poses challenges for surveillance. To compare WGS-based approaches with conventional typing for Salmonella surveillance, we performed concurrent WGS and multilocus variable-number tandem-repeat analysis (MLVA) of Salmonella Typhimurium isolates from the Australian Capital Territory (ACT) for a period of 5 months. We exchanged data via a central shared virtual machine and performed comparative genomic analyses. Epidemiological evidence was integrated with WGS-derived data to identify related isolates and sources of infection, and we compared WGS data for surveillance with findings from MLVA typing. We found that WGS data combined with epidemiological data linked an additional 9% of isolates to at least one other isolate in the study in contrast to MLVA and epidemiological data, and 19% more isolates than epidemiological data alone. Analysis of risk factors showed that in one WGS-defined cluster, human cases had higher odds of purchasing a single egg brand. While WGS was more sensitive and specific than conventional typing methods, we identified barriers to uptake of genomic surveillance around complexity of reporting of WGS results, timeliness, acceptability, and stability. In conclusion, WGS offers higher resolution of Salmonella Typhimurium laboratory surveillance than existing methods and can provide further evidence on sources of infection in case and outbreak investigations for public health action. However, there are several challenges that need to be addressed for effective implementation of genomic surveillance in Australia.


Assuntos
Surtos de Doenças , Genoma Bacteriano/genética , Infecções por Salmonella/epidemiologia , Salmonella typhimurium/genética , Austrália/epidemiologia , Técnicas de Tipagem Bacteriana , DNA Bacteriano/química , DNA Bacteriano/genética , Humanos , Repetições Minissatélites/genética , Estudos Prospectivos , Saúde Pública , Infecções por Salmonella/microbiologia , Salmonella typhimurium/isolamento & purificação , Sequenciamento Completo do Genoma
20.
Foodborne Pathog Dis ; 15(5): 285-292, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29638170

RESUMO

Salmonella Typhimurium is a common cause of foodborne illness in Australia. We report on seven outbreaks of Salmonella Typhimurium multilocus variable-number tandem-repeat analysis (MLVA) 03-26-13-08-523 (European convention 2-24-12-7-0212) in three Australian states and territories investigated between November 2015 and March 2016. We identified a common egg grading facility in five of the outbreaks. While no Salmonella Typhimurium was detected at the grading facility and eggs could not be traced back to a particular farm, whole genome sequencing (WGS) of isolates from cases from all seven outbreaks indicated a common source. WGS was able to provide higher discriminatory power than MLVA and will likely link more Salmonella Typhimurium cases between states and territories in the future. National harmonization of Salmonella surveillance is important for effective implementation of WGS for Salmonella outbreak investigations.


Assuntos
Surtos de Doenças , Ovos/microbiologia , Intoxicação Alimentar por Salmonella/epidemiologia , Salmonella typhimurium/genética , Austrália/epidemiologia , Genoma Bacteriano , Humanos , Repetições Minissatélites , Sequenciamento Completo do Genoma
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