The glyphosate controversy: an update / A controvérsia do glifosato: uma atualização

The demand for food in the world grows year after year due in part to population growth, but also to the improvement of emerging markets. Brazil is one of the largest food producers in the world. In 2017, its cereal, legume and oilseed crops totaled 238.6 million tons, 29.2% more than the year before. Much of the great increase in productivity is due to the incorporation of transgenic seeds, especially cotton, maize and soybean, which possess genes that will increase plant's adaptability to harsh soil and water conditions and, resistance to pests, but also tolerance to herbicides. Virtually, all transgenic soybeans planted in Brazil are resistant to glyphosate, the herbicide initially launched on the market by Monsanto in the 1970s under the trade name Roundup. Due to the existence of several transgenic crops tolerant to glyphosate, such as soy, wheat, corn and canola, this product is the most commercialized herbicide in the world. The use of glyphosate allows the sowing of transgenic crops immediately after application, making the planting and maintenance processes very practical. Soybeans, such as other transgenics, have biological safety already well defined, but the use of glyphosate is still an extremely controversial subject. This review presents some historical aspects of the binomial Roundup Ready soybean/glyphosate and discusses the most recent controversies about the use of glyphosate in Brazil and worldwide.(AU)

A demanda por alimentos no mundo cresce ano após ano devido em parte pelo aumento populacional, mas também pela melhoria dos mercados emergentes. O Brasil é um dos maiores produtores de alimentos do mundo. Em 2017, a safra nacional de cereais, leguminosas e oleaginosas totalizou 238,6 milhões de toneladas, 29,2% superior à obtida em 2016. Boa parte do grande aumento da produtividade se dá pela incorporação de sementes transgênicas, especialmente de algodão, milho e soja, que apresentam genes que conferem maior adaptabilidade da planta ao solo, pragas, condições hídricas, mas também conferem resistência a herbicidas. Praticamente toda a soja transgênica plantada no país é resistente ao glifosato, inicialmente lançado no mercado pela empresa Monsanto nos anos 1970 pelo nome comercial Roundup, que é hoje o herbicida mais utilizado no mundo, principalmente pela disseminação da soja e outros produtos transgênicos como trigo, milho e canola. A utilização do glifosato permite a semeadura de culturas transgênicas imediatamente após a aplicação, tornando o processo de plantio muito prático. A soja, como outros transgênicos, apresenta segurança biológica já definida, mas a utilização do glifosato ainda é um assunto extremamente controverso. Esta revisão apresenta alguns aspectos históricos do binômio soja transgênica Roundup Ready/glifosato e discute as controvérsias mais recentes sobre o uso do glifosato no Brasil e no mundo.(AU)

Chemoproteomic identification of molecular targets of antifungal prototypes, thiosemicarbazide and a camphene derivative of thiosemicarbazide, in Paracoccidioides brasiliensis.

Paracoccidioidomycosis (PCM) is a neglected human systemic disease caused by species of the genus Paracoccidioides. The disease attacks the host's lungs and may disseminate to many other organs. Treatment involves amphotericin B, sulfadiazine, trimethoprim-sulfamethoxazole, itraconazole, ketoconazole, or fluconazole. The treatment duration is usually long, from 6 months to 2 years, and many adverse effects may occur in relation to the treatment; co-morbidities and poor treatment adherence have been noted. Therefore, the discovery of more effective and less toxic drugs is needed. Thiosemicarbazide (TSC) and a camphene derivative of thiosemicarbazide (TSC-C) were able to inhibit P. brasiliensis growth at a low dosage and were not toxic to fibroblast cells. In order to investigate the mode of action of those compounds, we used a chemoproteomic approach to determine which fungal proteins were bound to each of these compounds. The compounds were able to inhibit the activities of the enzyme formamidase and interfered in P. brasiliensis dimorphism. In comparison with the transcriptomic and proteomic data previously obtained by our group, we determined that TSC and TSC-C were multitarget compounds that exerted effects on the electron-transport chain and cell cycle regulation, increased ROS formation, inhibited proteasomes and peptidases, modulated glycolysis, lipid, protein and carbohydrate metabolisms, and caused suppressed the mycelium to yeast transition.

Argentilactone Molecular Targets in Paracoccidioides brasiliensis Identified by Chemoproteomics.

Paracoccidioidomycosis (PCM) is the cause of many deaths from systemic mycoses. The etiological agents of PCM belong to the Paracoccidioides genus, which is restricted to Latin America. The infection is acquired through the inhalation of conidia that primarily lodge in the lungs and may disseminate to other organs and tissues. The treatment for PCM is commonly performed via the administration of antifungals such as amphotericin B, co-trimoxazole, and itraconazole. The antifungal toxicity and side effects, in addition to their long treatment times, have stimulated research for new bioactive compounds. Argentilactone is a compound that was isolated from the Brazilian savanna plant Hyptis ovalifolia, and it has been suggested to be a potent antifungal, inhibiting the dimorphism of P. brasiliensis and the enzymatic activity of isocitrate lyase, a key enzyme of the glyoxylate cycle. This work was developed due to the importance of elucidating the putative mode of action of argentilactone. The chemoproteomics approach via affinity chromatography was the methodology used to explore the interactions between P. brasiliensis proteins and argentilactone. A total of 109 proteins were identified and classified functionally. The most representative functional categories were related to amino acid metabolism, energy, and detoxification. Argentilactone inhibited the enzymatic activity of malate dehydrogenase, citrate synthase, and pyruvate dehydrogenase. Furthermore, argentilactone induces the production of reactive oxygen species and inhibits the biosynthesis of cell wall polymers.