Biosynthesis of silver nanoparticles mediated by entomopathogenic fungi: antimicrobial resistance, nanopesticides, and toxicity

Silver nanoparticles are widely used in the biomedical and agri-food fields due to their versatility. The use of biological methods for the synthesis of silver nanoparticles has increased considerably due to their feasibility and high biocompatibility. In general, microorganisms have been widely explored for the production of silver nanoparticles for several applications. The objective of this work was to evaluate the use of entomopathogenic fungi for the biological synthesis of silver nanoparticles, in comparison to the use of other filamentous fungi, and the possibility of using these nanoparticles as antimicrobial agents and for the control of insect pests. In addition, the in vitro methods commonly used to assess the toxicity of these materials are discussed. Several species of filamentous fungi are known to have the ability to form silver nanoparticles, but few studies have been conducted on the potential of entomopathogenic fungi to produce these materials. The investigation of the toxicity of silver nanoparticles is usually carried out in vitro through cytotoxicity/genotoxicity analyses, using well-established methodologies, such as MTT and comet assays, respectively. The use of silver nanoparticles obtained through entomopathogenic fungi against insects is mainly focused on mosquitoes that transmit diseases to humans, with satisfactory results regarding mortality estimates. Entomopathogenic fungi can be employed in the synthesis of silver nanoparticles for potential use in insect control, but there is a need to expand studies on toxicity so to enable their use also in insect control in agriculture.The work was funded by the Coordination for the Improvement of Higher Education Personnel (Capes); Sergipe Agricultural Development Company (Emdagro), the Industrial Biotechnology Program, University Tiradentes, Sergipe Technological Park (SergipeTec), and the Banco do Nordeste.info:eu-repo/semantics/publishedVersio

Blood-stage antiplasmodial activity and oocyst formation-blockage of metallo copper-cinchonine complex

In the fight against malaria, the key is early treatment with antimalarial chemotherapy, such as artemisinin-based combination treatments (ACTs). However, Plasmodium has acquired multidrug resistance, including the emergence of P. falciparum strains with resistance to ACT. The development of novel antimalarial molecules, that are capable of interfering in the asexual and sexual blood stages, is important to slow down the transmission in endemic areas. In this work, we studied the ability of the mettalo copper-cinchonine complex to interfere in the sexual and asexual stages of Plasmodium. The tested compound in the in vitro assay was a cinchonine derivative, named CinCu (Bis[Cinchoninium Tetrachlorocuprate(II)]trihydrate). Its biological functions were assessed by antiplasmodial activity in vitro against chloroquine-resistant P. falciparum W2 strain. The mice model of P. berghei ANKA infection was used to analyze the antimalarial activity of CinCu and chloroquine and their acute toxicity. The oocyst formation-blocking assay was performed by experimental infection of Anopheles aquasalis with P. vivax infected blood, which was treated with different concentrations of CinCu, cinchonine, and primaquine. We found that CinCu was able to suppress as high as 81.58% of parasitemia in vitro, being considered a molecule with high antiplasmodial activity and low toxicity. The in vivo analysis showed that CinCu suppressed parasitemia at 34% up to 87.19%, being a partially active molecule against the blood-stage forms of P. berghei ANKA, without inducing severe clinical signs in the treated groups. The transmission-blocking assay revealed that both cinchonine and primaquine were able to reduce the infection intensity of P. vivax in A. aquasalis, leading to a decrease in the number of oocysts recovered from the mosquitoes’ midgut. Regarding the effect of CinCu, the copper-complex was not able to induce inhibition of P. vivax infection; however, it was able to induce an important reduction in the intensity of oocyst formation by about 2.4 times. It is plausible that the metallo-compound also be able to interfere with the differentiation of parasite stages and/or ookinete-secreted chitinase into the peritrophic matrix of mosquitoes, promoting a reduction in the number of oocysts formed. Taken together, the results suggest that this compound is promising as a prototype for the development of new antimalarial drugs. Furthermore, our study can draw a new pathway for repositioning already-known antimalarial drugs by editing their chemical structure to improve the antimalarial activity against the asexual and sexual stages of the parasite

To what extent are ephippia of Mexican Anomopoda (Crustacea, Cladocera) identifiable?

Diapausing embryos encased within cladoceran ephippia result from sexual reproduction and increase genetic diversity. They are also important means by which species bypass harsh environmental conditions and disperse in space and time. Once released, ephippia usually sink to the benthos and remain there until hatching. Using the Sars’ method (incubating sediments to identify cladoceran hatchlings), ephippial egg bank biodiversity can be evaluated. Yet, even when samples are incubated under a variety of conditions, it is not possible to warrant that all have hatched. Few keys are available that facilitate the identification of cladocerans by using only ephippial morphology. Our goal was to analyze some cladoceran ephippia from Mexico, to develop a means to identify them using easily recognizable characteristics. Ephippia of 23 cladoceran species from waters in Aguascalientes (México) in 11 genera (Alona, Biapertura, Ceriodaphnia, Chydorus, Daphnia, Dunhevedia, Ilyocryptus, Macrothrix, Moina, Pleuroxus, and Simocephalus) were analyzed. In our analysis six morphological features were selected that permitted the identification of ephippia to species(-group) level. The results demonstrate that with a proper catalog of features, some ephippia can be identified

Gravidez na adolescência e o acesso às Tecnologias de Informação e Comunicação na Amazônia

Objetivo: Analisar a associação entre o acesso à informação, através da posse de computador com Internet nos domicílios e a gravidez na adolescência, tomando por referência os municípios da Amazônia legal brasileira em relação ao Brasil. Métodos: Estudo ecológico, baseado em dados obtidos do Censo Demográfico de pessoas e domicílios, realizado no Brasil no ano de 2010, pelo Instituto Brasileiro de Geografia e Estatística. Resultados: Para os municípios da Amazônia legal brasileira com os menores percentuais de domicílios com posse de computador com Internet ( 4,49%), a probabilidade de apresentar os maiores percentuais de gravidez na adolescência (≥ 9,39%) é de 0,723 enquanto para os demais municípios do Brasil é de 0,23. O fenômeno da gravidez na adolescência apresentou associação com espaço de referência (Brasil, Amazônia) e com a posse de computador com Internet nos domicílios. Conclusões: Os municípios da Amazônia legal brasileira apresentam elevados índices de ocorrência da gravidez na adolescência em relação aos demais municípios do Brasil. A ocorrência desse fenômeno, associada com a baixa infraestrutura de acesso à Internet, revela as desiguais condições que gestores e profissionais de saúde podem encontrar para executar projetos que utilizem as Tecnologias de Informação e Comunicação.Objectives: To analyze the association between access to information, measured by the possession of a computer with Internet connection in households, and teenage pregnancy, taking as reference the municipalities of the Brazilian Legal Amazon compared to the rest of Brazil. Methods: Ecological study based on data collected from the Demographic Census of persons and households, carried out in Brazil in 2010, by the Instituto Brasileiro de Geografia e Estatística (Brazilian Institute of Geography and Statistics). Results: For the municipalities of the Brazilian Legal Amazon with the lowest percentages of households with computer with Internet access ( 4.49%), the probability of presenting the highest percentages of teenage pregnancy (≥ 9.39%) is 0.723, while for the others municipalities of Brazil, this probability is 0.23. The phenomenon of teenage pregnancy presented association with the space of reference (Brazil, Amazon) and with the ownership of computer with Internet access in the households. Conclusions: The municipalities of the Brazilian Legal Amazon present high rates of teenage pregnancy compared to the others municipalities of Brazil. Associated to the poor infrastructure of Internet access, the occurrence of this phenomenon reveals the unequal conditions that managers and health professionals can find to execute projects that rely on Information and Communications Technologies

Insight into the Architecture of the NuRD Complex: Structure of the RbAp48-MTA1 Subcomplex

The nucleosome remodeling and deacetylase (NuRD) complex is a widely conserved transcriptional co-regulator that harbors both nucleosome remodeling and histone deacetylase activities. It plays a critical role in the early stages of ES cell differentiation and the reprogramming of somatic to induced pluripotent stem cells. Abnormalities in several NuRD proteins are associated with cancer and aging. We have investigated the architecture of NuRD by determining the structure of a subcomplex comprising RbAp48 and MTA1. Surprisingly, RbAp48 recognizes MTA1 using the same site that it uses to bind histone H4, showing that assembly into NuRD modulates RbAp46/48 interactions with histones. Taken together with other results, our data show that the MTA proteins act as scaffolds for NuRD complex assembly. We further show that the RbAp48-MTA1 interaction is essential for the in vivo integration of RbAp46/48 into the NuRD complex

The HBM4EU chromates study – Outcomes and impacts on EU policies and occupational health practices

Within the EU human biomonitoring initiative (HBM4EU), a targeted, multi-national study on occupational exposure to hexavalent chromium (Cr(VI)) was performed. Cr(VI) is currently regulated in EU under REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) and under occupational safety and health (OSH) legislation. It has recently been subject to regulatory actions to improve its risk management in European workplaces. Analysis of the data obtained within the HBM4EU chromates study provides support both for the implementation of these regulatory actions and for national enforcement programs and may also contribute to the updating of occupational limit values (OELs) and biological limit values for Cr(VI). It also provides useful insights on the contribution of different risk management measures (RMMs) to further reduce the exposure to Cr(VI) and may support the evaluation of applications for authorisation under REACH. Findings on chrome platers’ additional per- and polyfluoroalkyl substances (PFAS) exposure highlight the need to also pay attention to this substance group in the metals sector. A survey performed to evaluate the policy relevance of the HBM4EU chromates study findings supports the usefulness of the study results. According to the responses received from the survey, the HBM4EU chromates study was able to demonstrate the added value of the human biomonitoring (HBM) approach in assessment and management of occupational exposure to Cr(VI). For future occupational studies, we emphasise the need for engagement of policy makers and regulators throughout the whole research process to ensure awareness, relevance and uptake of the results in future policies.Highlights: Potential policy impact of the HBM4EU chromates study is presented and discussed; Surveyed policy makers confirmed policy relevance of biomonitoring results; Study considered to support national enforcement and further lowering of OELs; Added value of HBM in the management of occupational exposure to Cr(VI) was demonstrated; Close co-operation with regulators to support policy uptake is emphasised.Funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 733032 and received co-funding from the author's organizations and/or Ministries.info:eu-repo/semantics/publishedVersio

The HBM4EU chromates study – Outcomes and impacts on EU policies and occupational health practices

Funding Information: The recently completed EU human biomonitoring initiative (HBM4EU, www.hbm4eu.eu/about-hbm4eu/), was a European Joint Programme that aimed to harmonise the collection and use of biomonitoring data to better understand human exposure to chemicals in the environment, in occupational settings and through the use of consumer products to improve chemical risk assessment and management efforts, and to support policy making (Ganzleben et al., 2017). Within the context of the HBM4EU project several priority substances were selected for investigation based on the most important needs of policy makers and risk assessors, as well as common needs of participating countries and a broad range of other stakeholders including trade unions (Ougier et al., 2021). Many of the priority substances, along with having an important economic role, also pose health risks for workers due to their occupational use. One of the priority substances was hexavalent chromium (Cr(VI)), which was the main focus of the first of a series of three different HBM4EU occupational studies (Santonen et al. 2019a, 2022), the other two being focussed on electronic waste (E-waste) and diisocyanates exposures (Jones et al., 2022; Scheepers et al., 2021). In addition to Cr(VI), it was recognised that in chrome plating activities there may also be exposure to another group of HBM4EU priority chemicals, per- and polyfluoroalkyl substances (PFASs). PFASs, including PFOS (perfluorooctane sulfonate), have been used as mist suppressants in chrome plating baths to prevent the evaporation of Cr(VI) vapours (Blepp et al., 2017; Gluge et al., 2020). Although PFOS has now been largely replaced in the EU, many of its substitutes in chrome plating activities are also PFASs which may cause similar health and environmental concerns.Occupational exposure to Cr(VI) has been associated with an increased risk of lung and sinonasal cancers and is suspected to lead to gastrointestinal tract cancers (den Braver-Sewradj et al., 2021; ECHA 2013; IARC 2012). In addition, it is a common cause of occupational asthma, allergic dermatitis and there is a concern for adverse effects on reproductive health (Sun and Costa 2022). Exposure to Cr(VI) may occur in several occupational activities, e.g., in welding, Cr(VI) electroplating and other surface treatment processes such as paint application and removal of old paint containing Cr(VI) (SCOEL 2017). In order to limit the workers’ exposure to Cr(VI) in the EU, Cr(VI) is currently regulated under both the European regulation (EC 1907/2006) on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) and the EU Directive 2004/37/EC on the protection of workers from the risks related to exposure to carcinogens, mutagens or reprotoxic substances at work (CMRD) (EU 2004). The current binding Occupational Exposure Limit (OEL) set under the EU Directive 2004/37/EC is 10 μg/m3 (8-h time-weighted average (8-h TWA)) until January 17, 2025. After that period, the OEL (8-h TWA) will be reduced to 5 μg/m3. For welding, plasma-cutting processes and similar work processes that generate fumes, there is a derogation with an OEL of 25 μg/m³ (8-h TWA) until January 2025; after that date the OEL (8-h TWA) of 5 μg/m3 will be applicable. France, the Netherlands and Denmark already have stricter limits, with an OEL of 1 μg/m3 (8-h TWA) for Cr(VI) in all uses (Beskæftigelsesministeriet 2020; Ministère du travail, 2012; MinSZW 2016). In the US, the American Conference of Governmental Industrial Hygienists (ACGIH) has published, for inhalable Cr(VI) compounds, a threshold limit value (TLV) of 0.2 μg/m3 (8-h TWA) and a TLV Short-Term Exposure Limit (STEL) of 0.5 μg/m3 (ACGIH 2021). No EU-wide biological limit values (BLVs) for Cr(VI) are available, however some Member States have set BLVs for occupational exposure to Cr(VI), measured as urinary chromium (U–Cr). For example, France and Finland have derived BLVs of 2.5 μg/L and 10 μg/L corresponding to their respective OELs of 1 μg/m3 and 5 μg/m3 for Cr(VI) (ANSES 2017; STM 2020). The German Research Foundation (DFG 2020) has established biological exposure equivalents for carcinogenic substances (EKA values), ranging from 12 to 40 μg/L for U–Cr. These correspond to exposures ranging between 30 and 100 μg/m3 soluble alkaline chromate and/or Cr(VI) containing welding fumes over an 8-h work shift (Bolt and Lewalter 2012). Since these current national BLVs are mainly based on studies from plating workers, they include uncertainties especially concerning their applicability to workplaces other than the electroplating industry. One of the main aims of the HBM4EU chromates study was to provide EU relevant data on the current occupational Cr(VI) exposure to support the regulatory risk assessment and decision-making process. In addition, exposure to PFASs was evaluated in a subset of workers performing chrome plating activities.This project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 733032 and received co-funding from the author's organizations and/or Ministries. The project team would like to thank all the companies and workers who participated in the HBM4EU chromates study and all the experts who have contributed to the conduct of the study. Participants of the HBM4EU chromates study workshop and policy questionnaires are also acknowledged. Mr. Jouko Remes and Dr. Kia Gluschkoff (Finnish Institute of Occupational Health) are acknowledged for their assistance with the statistical analyses and figures. Funding Information: This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 733032 and received co-funding from the author's organizations and/or Ministries. Publisher Copyright: © 2022 The AuthorsWithin the EU human biomonitoring initiative (HBM4EU), a targeted, multi-national study on occupational exposure to hexavalent chromium (Cr(VI)) was performed. Cr(VI) is currently regulated in EU under REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) and under occupational safety and health (OSH) legislation. It has recently been subject to regulatory actions to improve its risk management in European workplaces. Analysis of the data obtained within the HBM4EU chromates study provides support both for the implementation of these regulatory actions and for national enforcement programs and may also contribute to the updating of occupational limit values (OELs) and biological limit values for Cr(VI). It also provides useful insights on the contribution of different risk management measures (RMMs) to further reduce the exposure to Cr(VI) and may support the evaluation of applications for authorisation under REACH. Findings on chrome platers’ additional per- and polyfluoroalkyl substances (PFAS) exposure highlight the need to also pay attention to this substance group in the metals sector. A survey performed to evaluate the policy relevance of the HBM4EU chromates study findings supports the usefulness of the study results. According to the responses received from the survey, the HBM4EU chromates study was able to demonstrate the added value of the human biomonitoring (HBM) approach in assessment and management of occupational exposure to Cr(VI). For future occupational studies, we emphasise the need for engagement of policy makers and regulators throughout the whole research process to ensure awareness, relevance and uptake of the results in future policies.publishersversionepub_ahead_of_prin

Human mitochondrial RNA turnover caught in flagranti: involvement of hSuv3p helicase in RNA surveillance

The mechanism of human mitochondrial RNA turnover and surveillance is still a matter of debate. We have obtained a cellular model for studying the role of hSuv3p helicase in human mitochondria. Expression of a dominant-negative mutant of the hSUV3 gene which encodes a protein with no ATPase or helicase activity results in perturbations of mtRNA metabolism and enables to study the processing and degradation intermediates which otherwise are difficult to detect because of their short half-lives. The hSuv3p activity was found to be necessary in the regulation of stability of mature, properly formed mRNAs and for removal of the noncoding processing intermediates transcribed from both H and L-strands, including mirror RNAs which represent antisense RNAs transcribed from the opposite DNA strand. Lack of hSuv3p function also resulted in accumulation of aberrant RNA species, molecules with extended poly(A) tails and degradation intermediates truncated predominantly at their 3′-ends. Moreover, we present data indicating that hSuv3p co-purifies with PNPase; this may suggest participation of both proteins in mtRNA metabolism

Cognitive disorders in patients with chronic kidney disease: Approaches to prevention and treatment

Background: Cognitive impairment is common in patients with chronic kidney disease (CKD), and early intervention may prevent the progression of this condition. Methods: Here, we review interventions for the complications of CKD (anemia, secondary hyperparathyroidism, metabolic acidosis, harmful effects of dialysis, the accumulation of uremic toxins) and for prevention of vascular events, interventions that may potentially be protective against cognitive impairment. Furthermore, we discuss nonpharmacological and pharmacological methods to prevent cognitive impairment and/or minimize the latter's impact on CKD patients' daily lives. Results: A particular attention on kidney function assessment is suggested during work-up for cognitive impairment. Different approaches are promising to reduce cognitive burden in patients with CKD but the availabe dedicated data are scarce. Conclusions: There is a need for studies assessing the effect of interventions on the cognitive function of patients with CKD