142 research outputs found

    Assessment of the ecotoxicological health status of Apis mellifera using a multi-tier approach based on biomarkers, proteomic analysis and quality and origin of bee products

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    Pollinating insects play a role of primary importance both in agriculture, ensuring the crops productivity, and in the conservation of plant biodiversity. Among pollinators, Apis mellifera L., 1958 (Hymenoptera: Apidae) is the most known and widespread species and the most valuable for its pollination service. This species is disappearing globally due to different reasons, such as climate change, the massive use of Plant Protection Products (PPPs) and other environmental contaminants diffusion, habitat fragmentation and parasites infections. The sub-lethal levels of pesticide residues and other anthropic contaminants, even not leading to the death of individuals, are able to cause problems in the development, behaviour and health of animals in the short and long term. Moreover, honey bees are exposed to mixtures of contaminants in the environment, that can cause different effects. However, there is a large gap in the assessment of the sub-lethal effects of these mixtures. Another gap in the research on the ecotoxicology of these animals is the assessment of the effects of commercial formulates instead of only using the active principles. Among the sub-lethal effects that were examined in the literature relating to pesticides exposure, rarely genotoxicity and immune system biomarkers were used. Anthropic activities could also be able to modify indirectly the quality and origin of bee products, since they can alter honey bees health and consequently their productivity. The use of an integrated approach to combine responses at different levels, could be a valid tool to evaluate the impact of contamination on these organisms. The goal of this thesis was to assess the health of honey bee colonies using a multi-tier methodology that included biomarker responses, proteomic analysis, and bee product quality and origin. This thesis was divided in two parts: ‚óŹ A laboratory study, exposing Apis mellifera specimens to two commercial pesticides, the fungicide Sakura¬ģ and the herbicide Elegant 2FD, alone and in combination. The effects of these compounds were assessed integrating two methodologies, consisting in a set of biomarkers and a proteomics approach. Both pesticides modulated the detoxification process. The fungicide alone had also effects on the metabolism, while the herbicide demonstrated to be neurotoxic. The results from the mixture treatments demonstrated that the effects obtained were influenced mostly by the herbicide. The proteomic approach revealed that the two pesticides were able to affect the energy metabolism, the immune system and the protein synthesis. The proteomic approach should be improved to understand if and to what extent the above-mentioned post-translational changes happened, using specific antibodies to perform a more specific assessment. ‚óŹ A two-year monitoring study, aiming to assess the ecotoxicological status of bees in natural environments. Apis mellifera specimens were sampled in 10 locations in Tuscany region characterised by varying contamination patterns. In this case, the used approach was made up of a set of biomarkers, used to assess the health status of honey bees, and the analyses of origin and quality of the honey, through melissopalynological and chemical-physical analyses. The biomarkers results obtained for the first year showed that the suburban area and the agricultural area were undergoing major stress but with different kinds of effects, probably because the contaminants were different in the various areas. In 2021 the specimens undergoing major stress were the ones coming from vineyards, that showed genotoxic effects, and clover field and wheat crops, showing alterations in nervous and immune systems. The comparison between the 2 years results showed that the organisms were undergoing major stress condition in 2021 compared to 2020. Bees from 2021 reported neurotoxic effects, the presence of oxidative stress and DNA damage. The different responses obtained could be due not only to contaminants but also to the changing of climatic conditions, such as differences in temperatures and rainfalls, which were also taken into consideration. The melissopalynological analysis showed that only in the clover field the pollen derived from the cultivation that we observed during the sampling. These findings suggest that the biomarker responses observed in A. mellifera specimens are probably not due to pollen contamination. In fact, organisms could come in contact with contaminants through other exposure routes. The carbohydrates, amino acids and humidity analysis showed that honey samples were not characterised by major differences, even if coming from different areas, except for the proportion of some amino acids, due to the presence of different pollens. Both the studies had also the goal to start filling a research gap regarding the assessment of effects on immune system and DNA damages, obtaining promising results. The integrated approaches that were used proved to be effective to observe the ecotoxicological health status of Apis mellifera from different points of view. The multi-trial approach would be a sensitive tool to measure sub-lethal effects, and not only lethal ones, of pesticide active principles and, more important, of pesticide commercial formulations. It would be helpful to improve the current risk assessment procedure for chemical registration and use, making the agricultural environment more pollinator-friendly

    The Comparative Toxicity, Biochemical and Physiological Impacts of Chlorantraniliprole and Indoxacarb on Mamestra brassicae (Lepidoptera: Noctuidae)

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    Background: The cabbage moth, Mamestra brassicae, is a polyphagous pest that attacks several crops. Here, the sublethal and lethal effects of chlorantraniliprole and indoxacarb were investigated on the developmental stages, detoxification enzymes, reproductive activity, calling behavior, peripheral physiology, and pheromone titer of M. brasssicae. Methods: To assess pesticide effects, the second instar larvae were maintained for 24 h on a semi-artificial diet containing insecticides at their LC10, LC30, and LC50 concentrations. Results: M. brassicae was more susceptible to chlorantraniliprole (LC50 = 0.35 mg/L) than indoxacarb (LC50 = 1.71 mg/L). A significantly increased developmental time was observed with both insecticides at all tested concentrations but decreases in pupation rate, pupal weight, and emergence were limited to the LC50 concentration. Reductions in both the total number of eggs laid per female and the egg viability were observed with both insecticides at their LC30 and LC50 concentrations. Both female calling activity and the sex pheromone (Z11-hexadecenyl acetate and hexadecenyl acetate) titer were significantly reduced by chlorantraniliprole in LC50 concentration. Antennal responses of female antennae to benzaldehyde and 3-octanone were significantly weaker than controls after exposure to the indoxocarb LC50 concentration. Significant reductions in the enzymatic activity of glutathione S-transferases, mixed-function oxidases, and carboxylesterases were observed in response to both insecticides

    Influence of Single-Nucleotide Polymorphisms on Clinical Outcomes of Capecitabine-Based Chemotherapy in Colorectal Cancer Patients: A Systematic Review

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    The aim of this systematic review was to provide a comprehensive overview of the literature published in the last decade on the association of single-nucleotide polymorphisms in genes involved in the pharmacodynamic and pharmacokinetic pathways of capecitabine with treatment outcomes among colorectal cancer patients. A systematic search of the literature published in the last 10 years was carried out in two databases (Medline and Scopus) using keywords related to the objective. Quality assessment of the studies included was performed using an assessment tool derived from the Strengthening the Reporting of Genetic Association (STREGA) statement. Thirteen studies were included in this systematic review. Genes involved in bioactivation, metabolism, transport, mechanism of action of capecitabine, DNA repair, and folate cycle were associated with toxicity. Meanwhile, genes related to DNA repair were associated with therapy effectiveness. This systematic review reveals that several SNPs other than the four DPYD variants that are screened in clinical practice could have an impact on treatment outcomes. These findings suggest the identification of future predictive biomarkers of effectiveness and toxicity in colorectal cancer patients treated with capecitabine. However, the evidence is sparse and requires further validationCo-funded by ERDF funds (EU) from the Instituto de Salud Carlos III (PT13/0010/0039)

    Biochemical responses, feeding and survival in the solitary bee Osmia bicornis following exposure to an insecticide and a fungicide alone and in combination

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    In agricultural ecosystems, bees are exposed to combinations of pesticides that may have been applied at different times. For example, bees visiting a flowering crop may be chronically exposed to low concentrations of systemic insecticides applied before bloom and then to a pulse of fungicide, considered safe for bees, applied during bloom. In this study, we simulate this scenario under laboratory conditions with females of the solitary bee, Osmia bicornis L. We studied the effects of chronic exposure to the neonicotinoid insecticide, Confidor (R) (imidacloprid) at a realistic concentration, and of a pulse (1 day) exposure of the fungicide Folicur (R) SE (tebuconazole) at field application rate. Syrup consumption, survival, and four biomarkers: acetylcholinesterase (AChE), carboxylesterase (CaE), glutathione S-transferase (GST), and alkaline phosphatase (ALP) were evaluated at two different time points. An integrated biological response (IBRv2) index was elaborated with the biomarker results. The fungicide pulse had no impact on survival but temporarily reduced syrup consumption and increased the IBRv2 index, indicating potential molecular alterations. The neonicotinoid significantly reduced syrup consumption, survival, and the neurological activity of the enzymes. The co-exposure neonicotinoid-fungicide did not increase toxicity at the tested concentrations. AChE proved to be an efficient biomarker for the detection of early effects for both the insecticide and the fungicide. Our results highlight the importance of assessing individual and sub-individual endpoints to better understand pesticide effects on bees

    Current and future therapeutic strategies for Alzheimer’s disease: an overview of drug development bottlenecks

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    Alzheimer‚Äôs disease (AD) is the most common chronic neurodegenerative disease worldwide. It causes cognitive dysfunction, such as aphasia and agnosia, and mental symptoms, such as behavioral abnormalities; all of which place a significant psychological and economic burden on the patients‚Äô families. No specific drugs are currently available for the treatment of AD, and the current drugs for AD only delay disease onset and progression. The pathophysiological basis of AD involves abnormal deposition of beta-amyloid protein (Aő≤), abnormal tau protein phosphorylation, decreased activity of acetylcholine content, glutamate toxicity, autophagy, inflammatory reactions, mitochondria-targeting, and multi-targets. The US Food and Drug Administration (FDA) has approved five drugs for clinical use: tacrine, donepezil, carbalatine, galantamine, memantine, and lecanemab. We have focused on the newer drugs that have undergone clinical trials, most of which have not been successful as a result of excessive clinical side effects or poor efficacy. Although aducanumab received rapid approval from the FDA on 7 June 2021, its long-term safety and tolerability require further monitoring and confirmation. In this literature review, we aimed to explore the possible pathophysiological mechanisms underlying the occurrence and development of AD. We focused on anti-Aő≤ and anti-tau drugs, mitochondria-targeting and multi-targets, commercially available drugs, bottlenecks encountered in drug development, and the possible targets and therapeutic strategies for future drug development. We hope to present new concepts and methods for future drug therapies for AD

    Advancing of risk assessment of pesticides on insect pollinators: beyond honey bees (Apis mellifera L.)

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    The western honey bee, Apis mellifera L., is currently the model specie for pesticide risk assessment on pollinators with the assumption that the worst-case scenarios for this species are sufficiently conservative to protect other insect pollinators. However, recent studies have showed that wild species may be more sensitive to plant protection products, due to differences in biology and life cycles. Therefore, there is the need to extend the risk assessment within a more ecological approach, in order to ensure that there are no irreversible effects on non-target organisms and in the environment. My dissertation aims to expand the risk assessment to other insect pollinators (including wild and managed pollinators), in order to cover some of the gaps of the current schemes. In this thesis, it is presented three experiments that cover the early stages of a solitary bee (chapter 1), the development of molecular tools for early detection of sub-lethal effects (chapter 2) and the development of protocols to access lethal and sub-lethal effects on other pollinator taxa (Diptera; chapter 3)

    Holocentric chromosomes in animals and plants: what do we know about these points outside the curve?

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    Usually, members of the Eukarya domain have kinetochores grouped at a single point, characterizing monocentric chromosomes. However, in some taxa the protein apparatus that composes the kinetochore is distributed continuously or discretely along the length of the chromosome, condition that defines holocentric chromosomes. The review aims to provide an overview of karyomorphological aspects of holocentric chromosomes in animals and plants, as well as an understanding of their origin, evolution and possible adaptive implications of their presence in eukaryotes. The main structural differences between holocentric and monocentric chromosomes concern the kinetochore proteins, the pattern of histone H3 phosphorylation and centromeric satellite DNA. The distribution of holocentric chromosomes in phylogenetic trees evidence their independent emergence numerous times throughout evolution. While many hypotheses have been created to explain the origin of holocentric chromosomes, none have been confirmed or refuted. Although the adaptive advantages generated by their presence are undeniable, especially in clastogenic environments, the typical behavior of chromosomes with diffuse kinetochores seems to be enough to make them the exception rather than the rule among eukaryotes

    Metal‚ąíOrganic Frameworks in Agriculture

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    The work has been supported by the MOFSEIDON project (PID2019-104228RB-100) funded by MCI/AEI/10.13039/ 501100011033/FEDER ‚ÄúUna manera de hacer Europa‚ÄĚ, ESENCE project (RTC2019-007254-5) funded by MCIN/ AEI/10.13039/501100011033), Junta de Andaluc√≠a (FQM- 394), and the Multifunctional Metallodrugs in Diagnosis and Therapy Network (MICIU, RED2018-102471-T). P.H. acknowledges the Spanish Ram√≥n y Cajal Programme (grant agreement 2014-15039). S.R. acknowledges the Spanish Juan de la Cierva Incorporaci√≥n Fellowship (grant agreement no. IJC2019-038894-I) funded by MCIN/AEI/10.13039/ 501100011033. Funding for open access charge: Universidad de Granada/CBUA.Agrochemicals, which are crucial to meet the world food qualitative and quantitative demand, are compounds used to kill pests (insects, fungi, rodents, or unwanted plants). Regrettably, there are some important issues associated with their widespread and extensive use (e.g., contamination, bioaccumulation, and development of pest resistance); thus, a reduced and more controlled use of agrochemicals and thorough detection in food, water, soil, and fields are necessary. In this regard, the development of new functional materials for the efficient application, detection, and removal of agrochemicals is a priority. Metal‚Äďorganic frameworks (MOFs) with exceptional sorptive, recognition capabilities, and catalytical properties have very recently shown their potential in agriculture. This Review emphasizes the recent advances in the use of MOFs in agriculture through three main views: environmental remediation, controlled agrochemical release, and detection of agrochemicals.MOFSEIDON project (PID2019-104228RB-100) funded by MCI/AEI/10.13039/ 501100011033/FEDERESENCE project (RTC2019-007254-5) funded by MCIN/ AEI/10.13039/501100011033Junta de Andaluc√≠a (FQM- 394), and the Multifunctional Metallodrugs in Diagnosis and Therapy Network (MICIU, RED2018-102471-T)Spanish Ram√≥n y Cajal Programme (grant agreement 2014-15039)Spanish Juan de la Cierva Incorporaci√≥n Fellowship (grant agreement no. IJC2019-038894-I) funded by MCIN/AEI/10.13039/ 501100011033Funding for open access charge: Universidad de Granada/CBU

    Caracterización del resistoma en el adenocarcinoma gástrico. Nuevas estrategias de quimiosensibilización

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    [ES]El c√°ncer de est√≥mago es una enfermedad agresiva y de mal pron√≥stico que causa m√°s de 700.000 muertes cada a√Īo en el mundo, ocupando la quinta posici√≥n en incidencia anual por tumores malignos. La mayor√≠a de los c√°nceres g√°stricos diagnosticados son adenocarcinomas (ACG) originados en las gl√°ndulas de la mucosa g√°strica. Su alta tasa de mortalidad se debe, principalmente, a que se diagnostican en estadios avanzados de la enfermedad cuando la resecci√≥n quir√ļrgica ya no es aconsejable. Adem√°s el tratamiento farmacol√≥gico disponible es poco eficaz debido a la alta quimiorresistencia que presenta el ACG. Existe una gran variedad de mecanismos de quimiorresistencia en las c√©lulas tumorales, que en ocasiones se presentan de forma simult√°nea en el tumor, pudiendo actuar de forma sin√©rgica. La consecuencia es la aparici√≥n del fenotipo de resistencia a m√ļltiples f√°rmacos (MDR, del ingl√©s Multidrug Resistance), que limita las opciones de tratamiento farmacol√≥gico y condiciona el pron√≥stico de los pacientes. La identificaci√≥n de la huella gen√©tica de quimiorresistencia (HGQT) del ACG podr√≠a ayudar a desarrollar estrategias de quimiosensibilizaci√≥n del tumor. La presencia en el ACG de niveles altos de expresi√≥n de la bomba de expulsi√≥n de f√°rmacos MRP4, podr√≠a desempe√Īar un papel relevante en el desarrollo de la farmacorresistencia de este tipo de tumores y constituir una diana farmacol√≥gica para el desarrollo de estrategias de quimiosensibilizaci√≥n. Aunque esta prote√≠na tiene la capacidad de reconocer como sustratos algunos f√°rmacos, se desconoce su papel en el transporte de los f√°rmacos antitumorales que se utilizan en el tratamiento de primera o segunda l√≠nea frente al ACG. Por otro lado, el desarrollo del fenotipo de malignidad del ACG que incluye aspectos como la proliferaci√≥n celular, la progresi√≥n del tumor y la falta de respuesta a los agentes farmacol√≥gicos esta favorecido por la aparici√≥n de alteraciones en la expresi√≥n de genes supresores de tumores. Teniendo en cuenta estos antecedentes, nos planteamos como objetivo global de esta Tesis Doctoral la identificaci√≥n de la HGQT del c√°ncer g√°strico, centr√°ndonos en el papel del transportoma en la quimiorresistencia del ACG, y en especial la prote√≠na MRP4, como base para el desarrollo de nuevas terapias quimiosensibilizantes de este tipo de tumor
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