Surfactant Aided Reductive Carbonylation of Nitrobenzene inWater Catalyzed by Pd Complexes

The catalytic carbonylation of nitroarenes is a field of high interest from a technological point of view, since provides an environmentally benign route to a number of important industrial products, such as isocyanates, carbamates, ureas, azoarenes and azoxyarenes, amines, amides, oximes and several types of heterocyclic compounds. The reductive carbonylation of nitrobenzene in water carried out by using Pd(II)-solvable catalyst precursors, leads to aniline, as major product. In the present paper we propose the micellar catalytic reductive carbonylation of nitrobenzene in water. The Pd(II) catalyst precursors tested are synthesized by using cheaper commercial insolvable ligands, such as triphenylphosphine (PPh3), 1,3- bis(diphenylphosphino)propane (dppp) and 1, 10-phenantroline (phen). The influence on the conversion and on the selectivity of such precursors has been evaluated in combination with commercial anionic (SDS), cationic (TBAB) and non ionic (Triton X 100) surfactants. We have found that all the Pd(II) complexes tested are efficiently dissolved in each O/W emulsions but the conversion is strongly influenced by the nature of ligand. By using Pd(OAc)2(PPh3)2, high selectivity towards azo- and azo-oxybenzene has been obtained. The influence of some reaction parameters has been further evaluated and optimized

The invasion of abandoned fields by a major alien tree filters understory plant traits in novel forest ecosystems

The abandonment of agricultural use is a common driver of spontaneous reforestation by alien trees. The N-fixing black locust (Robinia pseudoacacia L.) is a major alien invader of old fields in Europe. Here we show that canopy dominance by this tree may filter the frequency distribution of plant functional traits in the understory of secondary woodlands. Higher soil C/N ratio and available P are associated with black locust stands, while higher soil phenols associate with native tree stands. These environmental effects result in differences in understory flowering periods, reproduction types and life forms. Our findings emphasize the effect of a major alien tree on functional plant trait composition in the early stages of spontaneous reforestation of abandoned lands, implying the development of a novel forest ecosystem on a large geographical scale.Peer reviewe

Structure-activity relationship exploration of 3’-deoxy-7-deazapurine nucleoside analogues as anti-Trypanosoma brucei agents

Human African trypanosomiasis is a neglected tropical disease caused by Trypanosoma brucei parasites. These protists are unable to produce the purine ring, making them vulnerable to the effects of purine nucleoside analogues. Starting from 3'-deoxytubercidin (5), a lead compound with activity against central-nervous-stage human African trypanosomiasis, we investigate the structure-activity relationships of the purine and ribofuranose rings. The purine ring tolerated only modifications at C7, while from the many alterations of the 3'-deoxyribofuranosyl moiety only the arabino analogue 48 showed pronounced antitrypanosomal activity. Profiling of the most potent analogues against resistant T. brucei strains (resistant to pentamidine, diminazene, and isometamidium) showed reduced dependence on uptake mediated by the P2 aminopurine transporter relative to 5. The introduction of a 7-substituent confers up to 10-fold increased affinity for the P1 nucleoside transporter while generally retaining high affinity for P2. Four of the most promising analogues were found to be metabolically stable, earmarking them as suitable backup analogues for lead 5

6-O-alkylated 7-deazainosine nucleoside analogues : discovery of potent and selective anti-sleeping sickness agents

African trypanosomiasis, a deadly infectious disease caused by the protozoan Trypanosoma brucei spp., is spread to new hosts by bites of infected tsetse flies. Currently approved therapies all have their specific drawbacks, prompting a search for novel therapeutic agents. T. brucei lacks the enzymes necessary to forge the purine ring from amino acid precursors, rendering them dependent on the uptake and interconversion of host purines. This dependency renders analogues of purines and corresponding nucleosides an interesting source of potential anti-T. brucei agents. In this study, we synthesized and evaluated a series of 7-substituted 7-deazainosine derivatives and found that 6-O-alkylated analogues in particular showed highly promising in vitro activity with EC50 values in the mid-nanomolar range. SAR investigation of the O-alkyl chain showed that antitrypanosomal activity increased, and also cytotoxicity, with alkyl chain length, at least in the linear alkyl chain series. However, this could be attenuated by introducing a terminal branch point, resulting in the highly potent and selective analogues, 36, 37 and 38. No resistance related to transporter-mediated uptake could be identified, earmarking several of these analogues for further in vivo follow-up studies

DNA Methylation and Hydroxymethylation in Primary Colon Cancer and Synchronous Hepatic Metastasis

Colon cancer is one of the most frequent solid tumor and simultaneous diagnosis of primary colon cancer and liver metastases occurs in about one fourth of cases. The current knowledge on epigenetic signatures, especially those related to hydroxymethylation in primary cancer tissue, synchronous metastasis, and blood circulating cells is lacking. This study aimed to investigate both methylcytosine (mCyt) and hydroxymethylcytosine (hmCyt) status in the DNA of individual patients from colon cancer tissue, synchronous liver metastases, and in cancer-free colon and liver tissues and leukocytes. Patients undergoing curative surgery (n= 16) were enrolled and their laboratory and clinical history data collected. The contents of mCyt and hmCyt were determined by a liquid chromatography/mass spectrometry (LC/MS/MS) method in DNA extracted from primary colon cancer, synchronous hepatic metastatic tissues and homologous cancer-free tissues, i.e., colon and liver tissues as well as leukocytes. The mCyt and hmCyt levels were compared between cancerous and cancer-free tissues, and correlations between leukocytes and colon/liver tissues for both the mCyt and hmCyt levels were evaluated. The mCyt levels were similar in primary colon cancer and liver metastasis tissues (4.69 \ub1 0.37% vs. 4.77 \ub1 0.38%, respectively,p= 0.535), and both primary and metastatic tissues were hypomethylated compared to cancer-free colon (4.98 \ub1 0.26%). The difference in the mCyt content between cancerous and cancer-free colon tissues was significantly lower in primary colon cancer (p= 0.004), but not in liver metastasis (p= 0.148). The hmCyt content was similar in primary colon cancer compared to liver metastasis (0.035%, C.I. 0.024-0.052% versus 0.035%, C.I. 0.021-0.058%, respectively,p =0.905) and markedly depleted compared to the cancer-free colon (0.081%, C.I. 0.055-0.119%) with a statistically significant difference (p< 0.05) for both comparisons. The mCyt levels showed a borderline correlation between leukocytes and colon cancer tissue (Pearson's correlation coefficient = 0.51,p= 0.052) while no correlations were detected for the hmCyt levels. In conclusion, primary colon cancer and synchronous liver metastasis tissues showed a similar epigenetic status but were significantly hypomethylated and hypohydroxymethylated as compared to homologous cancer-free colon tissues

Diminazene resistance in Trypanosoma congolense is not caused by reduced transport capacity but associated with reduced mitochondrial membrane potential

Trypanosoma congolense is a principal agent causing livestock trypanosomiasis in Africa, costing developing economies billions of dollars and undermining food security. Only the diamidine diminazene and the phenanthridine isometamidium are regularly used, and resistance is widespread but poorly understood. We induced stable diminazene resistance in T. congolense strain IL3000 in vitro. There was no cross‐resistance with the phenanthridine drugs, melaminophenyl arsenicals, oxaborole trypanocides, or with diamidine trypanocides, except the close analogues DB829 and DB75. Fluorescence microscopy showed that accumulation of DB75 was inhibited by folate. Uptake of [3H]‐diminazene was slow, low affinity and partly but reciprocally inhibited by folate and by competing diamidines. Expression of T. congolense folate transporters in diminazene‐resistant T. b. brucei significantly sensitized the cells to diminazene and DB829, but not to oxaborole AN7973. However, [3H]‐diminazene transport studies, whole genome sequencing and RNA‐seq found no major changes in diminazene uptake, folate transporter sequence or expression. Instead, all resistant clones displayed a moderate reduction in the mitochondrial membrane potential. We conclude that diminazene uptake in T. congolense proceed via multiple low affinity mechanisms including folate transporters; while resistance is associated with a reduction in Ψm it is unclear whether this is the primary cause of the resistance

Global guidelines for the sustainable use of non-native trees to prevent tree invasions and mitigate their negative impacts

Sustainably managed non-native trees deliver economic and societal benefits with limited risk of spread to adjoining areas. However, some plantations have launched invasions that cause substantial damage to biodiversity and ecosystem services, while others pose substantial threats of causing such impacts. The challenge is to maximise the benefits of non-native trees, while minimising negative impacts and preserving future benefits and options. A workshop was held in 2019 to develop global guidelines for the sustainable use of non-native trees, using the Council of Europe – Bern Convention Code of Conduct on Invasive Alien Trees as a starting point. The global guidelines consist of eight recommendations: 1) Use native trees, or non-invasive non-native trees, in preference to invasive non-native trees; 2) Be aware of and comply with international, national, and regional regulations concerning non-native trees; 3) Be aware of the risk of invasion and consider global change trends; 4) Design and adopt tailored practices for plantation site selection and silvicultural management; 5) Promote and implement early detection and rapid response programmes; 6) Design and adopt tailored practices for invasive non-native tree control, habitat restoration, and for dealing with highly modified ecosystems; 7) Engage with stakeholders on the risks posed by invasive non-native trees, the impacts caused, and the options for management; and 8) Develop and support global networks, collaborative research, and information sharing on native and non-native trees. The global guidelines are a first step towards building global consensus on the precautions that should be taken when introducing and planting non-native trees. They are voluntary and are intended to complement statutory requirements under international and national legislation. The application of the global guidelines and the achievement of their goals will help to conserve forest biodiversity, ensure sustainable forestry, and contribute to the achievement of several Sustainable Development Goals of the United Nations linked with forest biodiversity

Positively selected modifications in the pore of TbAQP2 allow pentamidine to enter Trypanosoma brucei

Mutations in the Trypanosoma brucei aquaporin AQP2 are associated with resistance to pentamidine and melarsoprol. We show that TbAQP2 but not TbAQP3 was positively selected for increased pore size from a common ancestor aquaporin. We demonstrate that TbAQP2’s unique architecture permits pentamidine permeation through its central pore and show how specific mutations in highly conserved motifs affect drug permeation. Introduction of key TbAQP2 amino acids into TbAQP3 renders the latter permeable to pentamidine. Molecular dynamics demonstrates that permeation by dicationic pentamidine is energetically favourable in TbAQP2, driven by the membrane potential, although aquaporins are normally strictly impermeable for ionic species. We also identify the structural determinants that make pentamidine a permeant although most other diamidine drugs are excluded. Our results have wide-ranging implications for optimising antitrypanosomal drugs and averting cross-resistance. Moreover, these new insights in aquaporin permeation may allow the pharmacological exploitation of other members of this ubiquitous gene family

Stakeholders' views on the global guidelines for the sustainable use of non‐native trees

A large number of non‐native trees (NNTs) have been introduced globally and widely planted, contributing significantly to the world's economy. Although some of these species present a limited risk of spreading beyond their planting sites, a growing number of NNTs are spreading and becoming invasive leading to diverse negative impacts on biodiversity, ecosystem functions and human well‐being. To help minimize the negative impacts and maximize the economic benefits of NNTs, Brundu et al. developed eight guidelines for the sustainable use of NNTs globally—the Global Guidelines for the Use of NNTs (GG‐NNTs). Here, we used an online survey to assess perceptions of key stakeholders towards NNTs, and explore their knowledge of and compliance with the GG‐NNTs. Our results show that stakeholders are generally aware that NNTs can provide benefits and cause negative impacts, often simultaneously and they consider that their organization complies with existing regulations and voluntary agreements concerning NNTs. However, they are not aware of or do not apply most of the eight recommendations included in the GG‐NNTs. We conclude that effectively managing invasions linked to NNTs requires both more communication efforts using an array of channels for improving stakeholder awareness and implementation of simple measures to reduce NNT impacts (e.g. via GG‐NNTs), and a deeper understanding of the barriers and reluctance of stakeholders to manage NNT invasions. Read the free Plain Language Summary for this article on the Journal blog