Descriptor-and fragment-based QSAR models for a series of Schistosoma mansoni purine nucleoside inhibitors

The enzyme purine nucleoside phosphorylase from Schistosoma mansoni (SmPNP) is an attractive molecular target for the treatment of major parasitic infectious diseases, with special emphasis on its role in the discovery of new drugs against schistosomiasis, a tropical disease that affects millions of people worldwide. In the present work, we have determined the inhibitory potency and developed descriptor- and fragment-based quantitative structure-activity relationships (QSAR) for a series of 9-deazaguanine analogs as inhibitors of SmPNP. Significant statistical parameters (descriptor-based model: r² = 0.79, q² = 0.62, r²pred = 0.52; and fragment-based model: r² = 0.95, q² = 0.81, r²pred = 0.80) were obtained, indicating the potential of the models for untested compounds. The fragment-based model was then used to predict the inhibitory potency of a test set of compounds, and the predicted values are in good agreement with the experimental resultsA enzima purina nucleosídeo fosforilase de Schistosoma mansoni (SmPNP) é um alvo molecular atrativo para o tratamento de importantes doenças infecciosas parasitárias, com especial ênfase para o seu papel na descoberta de novos fármacos contra a esquistossomose, uma doença tropical que afeta cerca de 200 milhões de pessoas em 74 áreas endêmicas no mundo todo. No presente trabalho, a potência inibitória foi determinada e estudos das relações quantitativas entre a estrutura e atividade (QSAR), baseados em descritores e fragmentos, foram desenvolvidos para uma série de 9-deazaguaninas que atuam como inibidores da SmPNP. Parâmetros estatísticos significantes (modelo baseado em descritor: r² = 0,79; q² = 0,62, r²pred = 0,52; e modelo baseado em fragmento: r² = 0,95; q² = 0,81; r²pred = 0,80) foram obtidos, indicando o potencial dos modelos para compostos ainda não testados. O modelo baseado em fragmento foi então usado para predizer a potência inibitória de um conjunto teste de compostos, e os valores preditos estão em boa concordância com os resultados experimentais.Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB)(FAPESP) São Paulo Research Foundation(CNPq) National Council for Scientific and Technological Developmen

Drought avoidance and phenotypic flexibility of sweet potato (Ipomoea batatas (L.) Lam.) under water scarcity conditions

Sweet potato (Ipomoea batatas (L.) Lam.) is an important staple food in several regions of the world. Water scarcity is the most devastating abiotic stress, with a great impact on crop productivity, food security, and subsistence. Drought restricts the nutrient intake and transport into the plant. Tolerant crops have morphological mechanisms of drought avoidance and/or phenotypic flexibility, showing also good water and nutrient efficiency. However, that information is scarce for sweet potato, which is usually based on physiological traits of plant productivity. Here, we show the physiological responses of eight sweet potato accessions subjected to a 3 months’ drought period, by recording their differences for nutrient and leaf chlorophyll content, biomass and stress level. Our results showed that the differences in water use efficiency (WUE, +68.1%), chlorophyll content index (CCI, -5.3%), total plant biomass (TPB, -55.4%), nutrient efficiency (NER, +38.1%) and nutrient harvest index (NHI, +2.9%) where significantly correlated with the water regime. The water shortage led to a drought avoidance response, with TPB loss in all accessions. Distinct phenotypic flexibility responses were also recorded and explained by the root:shoot ratio (R:S) and stress index (SI) variation of the storage root and shoot growth. This information could be relevant for the development of sweet potato breeding programs, adapting this crop to climate change.info:eu-repo/semantics/publishedVersio

Drought Avoidance and Phenotypic Flexibility of Sweet Potato (Ipomoea batatas (L.) Lam.) Under Water Scarcity Conditions

Sweet potato (Ipomoea batatas (L.) Lam.) is an important staple food in several regions of the world. Water scarcity is the most devastating abiotic stress, with a great impact on crop productivity, food security, and subsistence. Drought restricts the nutrient intake and transport into the plant. Tolerant crops have morphological mechanisms of drought avoidance and/or phenotypic flexibility, showing also good water and nutrient efficiency. However, that information is scarce for sweet potato, which is usually based on physiological traits of plant productivity. Here, we show the physiological responses of eight sweet potato accessions subjected to a 3 months’ drought period, by recording their differences for nutrient and leaf chlorophyll content, biomass and stress level. Our results showed that the differences in water use efficiency (WUE, +68.1%), chlorophyll content index (CCI, -5.3%), total plant biomass (TPB, -55.4%), nutrient efficiency (NER, +38.1%) and nutrient harvest index (NHI, +2.9%) where significantly correlated with the water regime. The water shortage led to a drought avoidance response, with TPB loss in all accessions. Distinct phenotypic flexibility responses were also recorded and explained by the root:shoot ratio (R:S) and stress index (SI) variation of the storage root and shoot growth. This information could be relevant for the development of sweet potato breeding programs, adapting this crop to climate change

Phenotypic flexibility and drought avoidance in taro (Colocasia esculenta (L.) Schott)

Taro (Colocasia esculenta (L.) Schott) is a substantial staple food in most of the tropical regions. Prolonged exposure to drought impairs crop production worldwide. Tolerant crops have the best capability to cope and avoid drought, through phenotypic flexibility mechanisms. The water use efficiency (WUE) is well known in taro crops, but very scarce information is available relating to their nutrient efficiency (NER) in drought conditions. Our work provided pertinent information about the physiological variation of seven taro accessions subjected to seven months of drought, by recording the differences for nutrient allocation, chlorophyll canopy, biomass loss, and stress intensity. Significant relationships between control and drought treatments on WUE (+85%), total plant biomass (TPB, -26.8%), chlorophyll content index (CCI, +1.8%), and nutrient harvest index (NHI, +0.2%) were detected. Drought led to a generalized loss of TPB as drought avoidance strategy, although distinct phenotypic flexibility was observed through the root: shoot ratio (R:S) and stress index (SI) from the corm and shoot organs. The nutrient allocation from the corms to shoots, with NER increase registered in drought conditions, can be a valuable tool to complement the TPB and WUE productivity traits, to be used in taro breeding programs.info:eu-repo/semantics/publishedVersio

Natural Products-Based Drug Design against SARS-CoV-2 Mpro 3CLpro

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has received global attention due to the serious threat it poses to public health. Since the outbreak in December 2019, millions of people have been affected and its rapid global spread has led to an upsurge in the search for treatment. To discover hit compounds that can be used alone or in combination with repositioned drugs, we first analyzed the pharmacokinetic and toxicological properties of natural products from Brazil’s semiarid region. After, we analyzed the site prediction and druggability of the SARS-CoV-2 main protease (Mpro), followed by docking and molecular dynamics simulation. The best SARS-CoV-2 Mpro complexes revealed that other sites were accessed, confirming that our approach could be employed as a suitable starting protocol for ligand prioritization, reinforcing the importance of catalytic cysteine-histidine residues and providing new structural data that could increase the antiviral development mainly against SARSCoV-2. Here, we selected 10 molecules that could be in vitro assayed in response to COVID-19. Two compounds (b01 and b02) suggest a better potential for interaction with SARS-CoV-2 Mpro and could be further studied.Research Dean and Graduate Studies of the Federal University of Pará (PROPESP/UFPA)Brazilian National Council for Scientific and Technological Development (CNPq)Brazilian Coordination for Improvement of Personnel Higher Education (CAPES)Bahia Research Foundation (FAPESB, grant numbers APP071/2011, JCB-0039/2013, and RED-008/2013

Nematicidal activity of Paecilomyces marquandii proteases on infective larvae of Ancylostoma spp

ABSTRACT The present study aimed to evaluate the action of Paecilomyces marquandii proteases on Ancylostoma spp L3. White halos in the zymogram confirmed the proteolytic action. Difference (p <0.01) between the number of L3 in the differents groups was found, with 41.4% of reduction of Ancylostoma spp. L3 before 24 hours

Neutrophil Paralysis in Plasmodium vivax Malaria

Plasmodium vivax is responsible for approximately 60–80% of the malaria cases in the world, and contributes to significant social and economic instability in the developing countries of Latin America and Asia. The pathogenesis of P. vivax malaria is a consequence of host derived inflammatory mediators. Hence, a better understanding of the mechanisms involved in induction of systemic inflammation during P. vivax malaria is critical for the clinical management and prevention of severe disease. The innate immune receptors recognize Plasmodium sp. and initiate a broad spectrum of host defense mechanisms that mediate resistance to infection. However, the innate immune response is the classic “two-edged sword”, and clinical malaria is associated with high levels of circulating pro-inflammatory cytokines. Our findings show that both monocytes and neutrophils are highly activated during malaria. Monocytes produced high levels of IL-1β, IL-6 and TNF-α during acute malaria. On the other hand, neutrophils were a poor source of cytokines, but displayed an enhanced phagocytic activity and superoxide production. Unexpectedly, we noticed an impaired chemotaxis of neutrophils towards an IL-8 (CXCL8) gradient. We proposed that neutrophil paralysis is in part responsible for the enhanced susceptibility to bacterial infection observed in malaria patients

Adapting Agriculture to Climate Change: A Synopsis of Coordinated National Crop Wild Relative Seed Collecting Programs across Five Continents

The Adapting Agriculture to Climate Change Project set out to improve the diversity, quantity, and accessibility of germplasm collections of crop wild relatives (CWR). Between 2013 and 2018, partners in 25 countries, heirs to the globetrotting legacy of Nikolai Vavilov, undertook seed collecting expeditions targeting CWR of 28 crops of global significance for agriculture. Here, we describe the implementation of the 25 national collecting programs and present the key results. A total of 4587 unique seed samples from at least 355 CWR taxa were collected, conserved ex situ, safety duplicated in national and international genebanks, and made available through the Multilateral System (MLS) of the International Treaty on Plant Genetic Resources for Food and Agriculture (Plant Treaty). Collections of CWR were made for all 28 targeted crops. Potato and eggplant were the most collected genepools, although the greatest number of primary genepool collections were made for rice. Overall, alfalfa, Bambara groundnut, grass pea and wheat were the genepools for which targets were best achieved. Several of the newly collected samples have already been used in pre-breeding programs to adapt crops to future challenges.info:eu-repo/semantics/publishedVersio

2021 Taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales.

Correction to: 2021 Taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales. Archives of Virology (2021) 166:3567–3579. https://doi.org/10.1007/s00705-021-05266-wIn March 2021, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by four families (Aliusviridae, Crepuscuviridae, Myriaviridae, and Natareviridae), three subfamilies (Alpharhabdovirinae, Betarhabdovirinae, and Gammarhabdovirinae), 42 genera, and 200 species. Thirty-nine species were renamed and/or moved and seven species were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.This work was supported in part through Laulima Government Solutions, LLC prime contract with the US National Institute of Allergy and Infectious Diseases (NIAID) under Contract No. HHSN272201800013C. J.H.K. performed this work as an employee of Tunnell Government Services (TGS), a subcontractor of Laulima Government Solutions, LLC under Contract No. HHSN272201800013C. This work was also supported in part with federal funds from the National Cancer Institute (NCI), National Institutes of Health (NIH), under Contract No. 75N91019D00024, Task Order No. 75N91019F00130 to I.C., who was supported by the Clinical Monitoring Research Program Directorate, Frederick National Lab for Cancer Research. This work was also funded in part by Contract No. HSHQDC-15-C-00064 awarded by DHS S&T for the management and operation of The National Biodefense Analysis and Countermeasures Center, a federally funded research and development center operated by the Battelle National Biodefense Institute (V.W.); and NIH contract HHSN272201000040I/HHSN27200004/D04 and grant R24AI120942 (N.V., R.B.T.). S.S. acknowledges partial support from the Special Research Initiative of Mississippi Agricultural and Forestry Experiment Station (MAFES), Mississippi State University, and the National Institute of Food and Agriculture, US Department of Agriculture, Hatch Project 1021494. Part of this work was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC001030), the UK Medical Research Council (FC001030), and the Wellcome Trust (FC001030).S