99 research outputs found

    m6A RNA methylation facilitates pre-mRNA 3’-end formation and is essential for viability of Toxoplasma gondii

    Get PDF
    Toxoplasma gondii is an obligate intracellular parasite that can cause serious opportunistic disease in the immunocompromised or through congenital infection. To progress through its life cycle, Toxoplasma relies on multiple layers of gene regulation that includes an array of transcription and epigenetic factors. Over the last decade, the modification of mRNA has emerged as another important layer of gene regulation called epitranscriptomics. Here, we report that epitranscriptomics machinery exists in Toxoplasma, namely the methylation of adenosines (m6A) in mRNA transcripts. We identified novel components of the m6A methyltransferase complex and determined the distribution of m6A marks within the parasite transcriptome. m6A mapping revealed the modification to be preferentially located near the 3'-boundary of mRNAs. Knockdown of the m6A writer components METTL3 and WTAP resulted in diminished m6A marks and a complete arrest of parasite replication. Furthermore, we examined the two proteins in Toxoplasma that possess YTH domains, which bind m6A marks, and showed them to be integral members of the cleavage and polyadenylation machinery that catalyzes the 3'-end processing of pre-mRNAs. Loss of METTL3, WTAP, or YTH1 led to a defect in transcript 3'-end formation. Together, these findings establish that the m6A epitranscriptome is essential for parasite viability by contributing to the processing of mRNA 3'-ends

    Suscetibilidade de adultos de \u3ci\u3eBemisia tabaci\u3c/i\u3e biótipo B a inseticidas

    Get PDF
    A associação de alguns vírus fitopatogênicos com seus vetores pode ou não alterar a ação do controle químico. Este trabalho objetivou avaliar a suscetibilidade de moscas-brancas virulíferas (com aquisição do begomovírus Tomato severe rugose virus, ToSRV) e avirulíferas (sem aquisição do ToSRV) aos principais inseticidas registrados para o seu controle na cultura do tomateiro. Foram realizados ensaios com plantas de tomateiro e discos foliares de feijão- -de-porco. Os tratamentos foram arranjados em esquema fatorial de 7 (seis inseticidas + controle) e de 5 (quatro inseticidas + controle) x 2 [mosca-branca (MB) virulífera (V) ou avirulífera (AV)] e dispostos no delineamento em blocos ao acaso com seis e 25 repetições para o tomateiro e feijão-de-porco, respectivamente. Os inseticidas e concentrações avaliados foram: a) tomateiro: acefato (100 g), clotianidina (20 g), pimetrozina (40 g), piriproxifem (75 mL) e tiametoxam (20 g de i.a./100 L de calda) e diafentiurom (800 g de i.a./300 L de calda); b) feijão-de-porco: acefato (100 g), tiametoxam (20 g), pimetrozina (40 g de i.a./100 L) e diafentiurom (800 g de i.a./300 L de calda). Não houve diferença na suscetibilidade do vetor em razão de sua condição (V ou AV). Os inseticidas diafentiurom (87,68%±4,96) e tiametoxam (43,95%±9,43) proporcionaram maior mortalidade de MB no tomateiro, enquanto no feijão-de-porco diafentiurom (92,01%±2,68) e tiametoxam (86,39%±2,74) apresentaram desempenho similar. Diafentiurom foi o único inseticida que proporcionou controle satisfatório de B. tabaci em ambos os ensaios avaliados. The association between some plant pathogenic viruses and their vectors may or may not alter the action of chemical control. This study aimed at evaluating the susceptibility of viruliferous (transmitter of the begomovirus Tomato severe rugose virus, ToSRV) and aviruliferous (non-transmitter of ToSRV) Bemisia tabaci biotype B to the main insecticides registered to its control in tomato crops. Two sets of experiments were carried out with tomato plants and foliar discs of jack beans. The treatments were schemed in a factorial design of 7 (six insecticides + control) and 5 (four insecticides + control) x 2 [viruliferous (V) or aviruliferous (AV) whiteflies (WF)] and arranged in completely randomized blocks design with six and 25 replications, respectively, for tomato and jack beans. The following insecticides and concentrations were evaluated: a) tomato: acephate (100 g), clothianidin (20 g), pymetrozine (40 g), pyriproxyfen (75 mL) and thiametoxan (20 g of a.i./100 L), and diafenthiuron (800 g of a.i./300 L of solution); b) jack beans: acephate (100 g), thiametoxan (20 g), pymetrozine (40 g of a.i./100 L) and diafenthiuron (800 g of a.i./300 L). The insecticide susceptibility of whiteflies was not altered by their viruliferous condition (V or AV). The insecticides diafenthiuron (87.68%±4.96) and thiametoxam (43.94%±9.43) caused the highest mortality of whiteflies in tomatoes. In jack beans, diafenthiuron (92.01%±2.68) and thiametoxam (86,39%±2,74) caused similar mortality. Among the tested insecticides, diafenthiuron was the only one causing significant mortality of B. tabaci biotype B

    Suscetibilidade de adultos de \u3ci\u3eBemisia tabaci\u3c/i\u3e biótipo B a inseticidas

    Get PDF
    A associação de alguns vírus fitopatogênicos com seus vetores pode ou não alterar a ação do controle químico. Este trabalho objetivou avaliar a suscetibilidade de moscas-brancas virulíferas (com aquisição do begomovírus Tomato severe rugose virus, ToSRV) e avirulíferas (sem aquisição do ToSRV) aos principais inseticidas registrados para o seu controle na cultura do tomateiro. Foram realizados ensaios com plantas de tomateiro e discos foliares de feijão- -de-porco. Os tratamentos foram arranjados em esquema fatorial de 7 (seis inseticidas + controle) e de 5 (quatro inseticidas + controle) x 2 [mosca-branca (MB) virulífera (V) ou avirulífera (AV)] e dispostos no delineamento em blocos ao acaso com seis e 25 repetições para o tomateiro e feijão-de-porco, respectivamente. Os inseticidas e concentrações avaliados foram: a) tomateiro: acefato (100 g), clotianidina (20 g), pimetrozina (40 g), piriproxifem (75 mL) e tiametoxam (20 g de i.a./100 L de calda) e diafentiurom (800 g de i.a./300 L de calda); b) feijão-de-porco: acefato (100 g), tiametoxam (20 g), pimetrozina (40 g de i.a./100 L) e diafentiurom (800 g de i.a./300 L de calda). Não houve diferença na suscetibilidade do vetor em razão de sua condição (V ou AV). Os inseticidas diafentiurom (87,68%±4,96) e tiametoxam (43,95%±9,43) proporcionaram maior mortalidade de MB no tomateiro, enquanto no feijão-de-porco diafentiurom (92,01%±2,68) e tiametoxam (86,39%±2,74) apresentaram desempenho similar. Diafentiurom foi o único inseticida que proporcionou controle satisfatório de B. tabaci em ambos os ensaios avaliados. The association between some plant pathogenic viruses and their vectors may or may not alter the action of chemical control. This study aimed at evaluating the susceptibility of viruliferous (transmitter of the begomovirus Tomato severe rugose virus, ToSRV) and aviruliferous (non-transmitter of ToSRV) Bemisia tabaci biotype B to the main insecticides registered to its control in tomato crops. Two sets of experiments were carried out with tomato plants and foliar discs of jack beans. The treatments were schemed in a factorial design of 7 (six insecticides + control) and 5 (four insecticides + control) x 2 [viruliferous (V) or aviruliferous (AV) whiteflies (WF)] and arranged in completely randomized blocks design with six and 25 replications, respectively, for tomato and jack beans. The following insecticides and concentrations were evaluated: a) tomato: acephate (100 g), clothianidin (20 g), pymetrozine (40 g), pyriproxyfen (75 mL) and thiametoxan (20 g of a.i./100 L), and diafenthiuron (800 g of a.i./300 L of solution); b) jack beans: acephate (100 g), thiametoxan (20 g), pymetrozine (40 g of a.i./100 L) and diafenthiuron (800 g of a.i./300 L). The insecticide susceptibility of whiteflies was not altered by their viruliferous condition (V or AV). The insecticides diafenthiuron (87.68%±4.96) and thiametoxam (43.94%±9.43) caused the highest mortality of whiteflies in tomatoes. In jack beans, diafenthiuron (92.01%±2.68) and thiametoxam (86,39%±2,74) caused similar mortality. Among the tested insecticides, diafenthiuron was the only one causing significant mortality of B. tabaci biotype B

    Influence of Ecto-Nucleoside Triphosphate Diphosphohydrolase Activity on Trypanosoma cruzi Infectivity and Virulence

    Get PDF
    The protozoan Trypanosoma cruzi is the causative agent of Chagas disease, an endemic zoonosis present in some countries of South and Central Americas. The World Health Organization estimates that 100 million people are at risk of acquiring this disease. The infection affects mainly muscle tissues in the heart and digestive tract. There are no vaccines or effective treatment, especially in the chronic phase when most patients are diagnosed, which makes a strong case for the development of new drugs to treat the disease. In this work we evaluate a family of proteins called Ecto-Nucleoside-Triphosphate-Diphosphohydrolase (Ecto-NTPDase) as new chemotherapy target to block T. cruzi infection in mammalian cells and in mice. We have used inhibitors and antibodies against this protein and demonstrated that T. cruzi Ecto-NTPDases act as facilitators of infection in mammalian cells and virulence factors in mice model. Two of the drugs used in this study (Suramin and Gadolinium) are currently used for other diseases in humans, supporting the possibility of their use in the treatment of Chagas disease

    Pervasive gaps in Amazonian ecological research

    Get PDF

    Pervasive gaps in Amazonian ecological research

    Get PDF
    Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

    Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

    Get PDF
    Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

    Pervasive gaps in Amazonian ecological research

    Get PDF
    Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost
    corecore