RESUMO
Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) share many clinical, pathological, and genetic features, but a detailed understanding of their associated transcriptional alterations across vulnerable cortical cell types is lacking. Here, we report a high-resolution, comparative single-cell molecular atlas of the human primary motor and dorsolateral prefrontal cortices and their transcriptional alterations in sporadic and familial ALS and FTLD. By integrating transcriptional and genetic information, we identify known and previously unidentified vulnerable populations in cortical layer 5 and show that ALS- and FTLD-implicated motor and spindle neurons possess a virtually indistinguishable molecular identity. We implicate potential disease mechanisms affecting these cell types as well as non-neuronal drivers of pathogenesis. Finally, we show that neuron loss in cortical layer 5 tracks more closely with transcriptional identity rather than cellular morphology and extends beyond previously reported vulnerable cell types.
Assuntos
Esclerose Lateral Amiotrófica , Degeneração Lobar Frontotemporal , Córtex Pré-Frontal , Animais , Humanos , Camundongos , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/patologia , Demência Frontotemporal/genética , Degeneração Lobar Frontotemporal/genética , Degeneração Lobar Frontotemporal/metabolismo , Degeneração Lobar Frontotemporal/patologia , Perfilação da Expressão Gênica , Neurônios/metabolismo , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/patologia , Análise da Expressão Gênica de Célula ÚnicaRESUMO
Chorea-acanthocytosis (ChAc) and McLeod syndrome are diseases with shared clinical manifestations caused by mutations in VPS13A and XK, respectively. Key features of these conditions are the degeneration of caudate neurons and the presence of abnormally shaped erythrocytes. XK belongs to a family of plasma membrane (PM) lipid scramblases whose action results in exposure of PtdSer at the cell surface. VPS13A is an endoplasmic reticulum (ER)-anchored lipid transfer protein with a putative role in the transport of lipids at contacts of the ER with other membranes. Recently VPS13A and XK were reported to interact by still unknown mechanisms. So far, however, there is no evidence for a colocalization of the two proteins at contacts of the ER with the PM, where XK resides, as VPS13A was shown to be localized at contacts between the ER and either mitochondria or lipid droplets. Here we show that VPS13A can also localize at ER-PM contacts via the binding of its PH domain to a cytosolic loop of XK, that such interaction is regulated by an intramolecular interaction within XK, and that both VPS13A and XK are highly expressed in the caudate neurons. Binding of the PH domain of VPS13A to XK is competitive with its binding to intracellular membranes that mediate other tethering functions of VPS13A. Our findings support a model according to which VPS13A-dependent lipid transfer between the ER and the PM is coupled to lipid scrambling within the PM. They raise the possibility that defective cell surface exposure of PtdSer may be responsible for neurodegeneration.
Assuntos
Proteínas de Transporte , Membrana Celular , Lipídeos , Proteínas de Transporte Vesicular , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Membrana Celular/metabolismo , Retículo Endoplasmático/enzimologia , Retículo Endoplasmático/metabolismo , Humanos , Neuroacantocitose/metabolismo , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismoRESUMO
The mechanisms by which mutant huntingtin (mHTT) leads to neuronal cell death in Huntington's disease (HD) are not fully understood. To gain new molecular insights, we used single nuclear RNA sequencing (snRNA-seq) and translating ribosome affinity purification (TRAP) to conduct transcriptomic analyses of caudate/putamen (striatal) cell type-specific gene expression changes in human HD and mouse models of HD. In striatal spiny projection neurons, the most vulnerable cell type in HD, we observe a release of mitochondrial RNA (mtRNA) (a potent mitochondrial-derived innate immunogen) and a concomitant upregulation of innate immune signaling in spiny projection neurons. Further, we observe that the released mtRNAs can directly bind to the innate immune sensor protein kinase R (PKR). We highlight the importance of studying cell type-specific gene expression dysregulation in HD pathogenesis and reveal that the activation of innate immune signaling in the most vulnerable HD neurons provides a novel framework to understand the basis of mHTT toxicity and raises new therapeutic opportunities.
Assuntos
Proteína Huntingtina/imunologia , Doença de Huntington/imunologia , Imunidade Inata/imunologia , Neurônios/imunologia , RNA Mitocondrial/imunologia , Animais , Humanos , Proteína Huntingtina/genética , Doença de Huntington/genética , Doença de Huntington/patologia , Camundongos , Mutação , Neurônios/patologia , TranscriptomaRESUMO
Huntington's disease (HD) is an incurable neurodegenerative disorder caused by CAG trinucleotide expansions in the huntingtin gene. Markers of both systemic and CNS immune activation and inflammation have been widely noted in HD and mouse models of HD. In particular, elevation of the pro-inflammatory cytokine interleukin-6 (IL-6) is the earliest reported marker of immune activation in HD, and this elevation has been suggested to contribute to HD pathogenesis. To test the hypothesis that IL-6 deficiency would be protective against the effects of mutant huntingtin, we generated R6/2 HD model mice that lacked IL-6. Contrary to our prediction, IL-6 deficiency exacerbated HD-model associated behavioral phenotypes. Single nuclear RNA Sequencing (snRNA-seq) analysis of striatal cell types revealed that IL-6 deficiency led to the dysregulation of various genes associated with synaptic function, as well as the BDNF receptor Ntrk2. These data suggest that IL-6 deficiency exacerbates the effects of mutant huntingtin through dysregulation of genes of known relevance to HD pathobiology in striatal neurons, and further suggest that modulation of IL-6 to a level that promotes proper regulation of genes associated with synaptic function may hold promise as an HD therapeutic target.
Assuntos
Encéfalo/metabolismo , Doença de Huntington/metabolismo , Interleucina-6/deficiência , Fenótipo , Animais , Encéfalo/fisiopatologia , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Doença de Huntington/genética , Interleucina-6/metabolismo , Camundongos TransgênicosRESUMO
Unbiased in vivo genome-wide genetic screening is a powerful approach to elucidate new molecular mechanisms, but such screening has not been possible to perform in the mammalian central nervous system (CNS). Here, we report the results of the first genome-wide genetic screens in the CNS using both short hairpin RNA (shRNA) and CRISPR libraries. Our screens identify many classes of CNS neuronal essential genes and demonstrate that CNS neurons are particularly sensitive not only to perturbations to synaptic processes but also autophagy, proteostasis, mRNA processing, and mitochondrial function. These results reveal a molecular logic for the common implication of these pathways across multiple neurodegenerative diseases. To further identify disease-relevant genetic modifiers, we applied our screening approach to two mouse models of Huntington's disease (HD). Top mutant huntingtin toxicity modifier genes included several Nme genes and several genes involved in methylation-dependent chromatin silencing and dopamine signaling, results that reveal new HD therapeutic target pathways.
Assuntos
Sobrevivência Celular/genética , Proteína Huntingtina/genética , Doença de Huntington/genética , Neostriado/metabolismo , Neurônios/metabolismo , Animais , Comportamento Animal , Sistemas CRISPR-Cas , Técnicas de Silenciamento de Genes , Biblioteca Gênica , Genes Essenciais/genética , Camundongos , Camundongos Transgênicos , Nucleosídeo NM23 Difosfato Quinases/genética , Nucleosídeo Difosfato Quinase D/genética , Agregados Proteicos , Interferência de RNA , RNA Guia de Cinetoplastídeos , RNA Interferente Pequeno , Receptores de Dopamina D2/genética , Análise de Sequência de RNARESUMO
Predation by Engytatus varians (Distant) adults on different development stages of the prey species Bactericera cockerelli (Sulcer) (egg, second, and third nymphal instars), Spodoptera exigua (Hübner) and Spodoptera frugiperda (J. E. Smith) (egg, first, and second larval instars) was evaluated using tomato (Solanum lycopersicum L.) leaflets or plants. These insects are the primary pest of several agriculturally important crops. The influence of E. varians age on the predation capacity was also analysed. Engytatus varians females consumed significantly more B. cockerelli eggs and nymphs than males. Additionally, female predators consumed significantly more second than third instar prey at two predator ages, while males consumed significantly more the second instar than third instar prey at all predator ages. In most of the cases, females also consumed significantly more S. exigua and S. frugiperda eggs than males; however, in terms of larvae consumption, this difference was observed only in some predator ages. Females consumed more the first than second instar S. exigua than males, whereas this behaviour was only observed in males when the predators were 15 and 17 days old. No significant differences were observed in the consumption of first and second instar of S. frugiperda for both sexes of the predators. Predator age did not cause any systematic effects on the predation rates of any prey species. Based on these results, we confirmed that E. varians has potential as a biological control agent for B. cockerelli and also for the Spodoptera species bioassayed.
Assuntos
Hemípteros , Comportamento Predatório , Spodoptera , Animais , Feminino , Larva , Masculino , Ninfa , ÓvuloRESUMO
The measurement of surface photovoltage (SPV) transients over 12 orders of magnitude in time was recently demonstrated [Rev. Sci. Instrum. 88, 053904 (2017)]. In dedicated experiments, however, a high-impedance buffer shall be placed outside the measurement chamber, which has consequences for SPV measurements at very short times. By varying the LCR circuit of a measurement configuration, applying a multi-parameter fit and simulating the corresponding SPV transients, we show, on the examples of highly doped silicon and a CdS thin film, that the source function of SPV transients can be reconstructed with a resolution time better than 1 ns.
RESUMO
Aims: To determine the impact of permanent cardiac pacing after transcatheter aortic valve implantation (TAVI) with the CoreValveTM prosthesis in terms of all-cause mortality and morbidity [rehospitalizations for heart failure (HF) or stroke] at the long-term follow-up. Methods and results: The prospective analysis comprised 259 patients (138 women, 53.3%, age 78 ± 6 years) treated by a CoreValveTM prosthesis from April 2008 to December 2015. Forty-two patients were excluded for analysis: 9 with pre-existing permanent pacemaker (PPM) implantation, 19 who required a PPM during the follow-up and 14 patients because of hospital mortality during or after the CoreValveTM prosthesis implantation procedure. The remaining 217 patients were divided in two groups: Group-1 included those patients who required a PPM immediately after TAVI, and Group-2 included those patients who did not require permanent cardiac pacing at the long-term follow-up. Patients received follow-up at 1-month, 6-months, 12-months, and yearly thereafter. A total of 39 patients required a PPM immediately after TAVI (15.0%), but 178 patients (68.7%) did not. The mean follow-up was 37 ± 27 months (range 3-99 months) in both groups. There was no difference between the two groups in terms of all-cause mortality (52.6% vs. 56.8%, P = 0.125; HR 1.22 [0.87-1.77, 95% CI]), or stroke (13.3% vs. 15.1% P = 0.842; HR 1.12 [0.37-3.32, 95% CI]). However, patients who underwent PPM implantation developed an increase in readmissions for HF (21.1% vs. 31.9%, P = 0.015; HR 1.82 [1.23-3.92, 95% CI]). Conclusion: Patients requiring a PPM after TAVI did not have an increase in mortality, or an increase in the likelihood of developing a stroke at a long-term follow-up. However, this subgroup of patients showed an increase in rehospitalization due to HF at medium- and long-term follow-up.
Assuntos
Estenose da Valva Aórtica , Valva Aórtica , Estimulação Cardíaca Artificial/métodos , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/cirurgia , Cateterismo Cardíaco/métodos , Feminino , Humanos , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Readmissão do Paciente/estatística & dados numéricos , Desenho de Prótese , Risco Ajustado/métodos , Espanha/epidemiologia , Tempo , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/instrumentação , Substituição da Valva Aórtica Transcateter/métodosRESUMO
This study describes four multiple nucleocapsid nucleopolyhedrovirus isolates recovered from infected larvae of beet armyworm, Spodoptera exigua (Hübner) (Lepidoptera: Noctuidae), on crops in two different geographical regions of Mexico. Molecular and biological characterization was compared with characterized S. exigua multiple nucleopolyhedrovirus (SeMNPV) isolates from the United States (SeUS1 and SeUS2) and Spain (SeSP2). Restriction endonuclease analysis of viral DNA confirmed that all Mexican isolates were SeMNPV isolates, but molecular differences between the Mexican and the reference isolates were detected using PCR combined with restriction fragment length polymorphism (RFLP). Amplification of the variable region V01 combined with RFLP distinguished the two Mexican isolates, SeSLP6 and SeSIN6. BglII digestions showed that the majority of the isolates contained submolar bands, indicating the presence of genetic heterogeneity. Amplification of the variable regions V04 and V05 distinguished between American and the Spanish isolates. Biological characterization was performed against two laboratory colonies of S. exigua, one from Mexico, and another from Switzerland. Insects from the Mexican colony were less susceptible to infection than insects from Se-Swiss colony. In the Se-Mex colony, SeSP2 was the most pathogenic isolate followed by SeSIN6, although their virulence was similar to most of the isolates tested. In Se-Swiss colony, similar LD50 values were observed for the five isolates, although the virulence was higher for the SeSLP6 isolate, which also had the highest OB (occlusion body) yield. We conclude that the Mexican isolates SeSIN6 and SeSLP6 possess insecticidal traits of value for the development of biopesticides for the control of populations of S. exigua.
Assuntos
DNA Viral/genética , Nucleopoliedrovírus/fisiologia , Controle Biológico de Vetores , Spodoptera/virologia , Animais , Larva/crescimento & desenvolvimento , Larva/virologia , México , Nucleopoliedrovírus/genética , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Spodoptera/crescimento & desenvolvimentoRESUMO
Introducción: La residencia médica es un período de riesgo para el desarrollo de problemas de salud mental. Los estudios de ansiedad en residentesson contrastantes; sin embargo, se cree que los niveles de ansiedad son altos ya que los programas se desarrollan en hospitales nacionales que carecende recursos fsicos, materiales y humanos. El objetvo del presente estudio es determinar los niveles de ansiedad en médicos residentes en diferentesespecialidades empleando el cuestonario inventario de la ansiedad rasgo-estado (IDARE).Métodos: Se administró una encuesta electrónica para determinar el nivel de ansiedad en médicos residentes en diferentes especialidades del HospitalGeneral San Juan de Dios.Resultados: Se obtuvieron 132 encuestas para el análisis. La mayoría de los médicos encuestados son hombres (59%), solteros (83%) que no tenendependientes (79%), cursan residencia de cirugía o medicina interna (54%), trabajan más de 80 horas por semana (85%) y viajan menos de una horapara llegar al lugar de residencia (67%). El promedio del nivel de ansiedad-estado de los médicos residentes fue 46.94 puntos, mientras que el nivelpromedio de ansiedad-rasgo fue de 42.77 puntos. El 35% de los residentes poseen niveles de ansiedad medio y 59% altos en el momento de responderla encuesta; y el 56% posee niveles de ansiedad medio y 37% alto generalmente. No se encontró diferencia estadístcamente signifcatva en los nivelesde ansiedad en base a género, estado civil, tpo de residencia, dependientes y horas de tráfco. La única variable asociada con ansiedad fue la cantdadde horas de trabajo por semana.Conclusiones: La mayoría de los residentes encuestados poseen niveles de ansiedad medio-altos, la única variable asociada con niveles de ansiedadfue la cantdad de horas de trabajo por semana.
Background: Medical residency is a risky period for the development of mental health problems. Although anxiety studies in medical residents areinconclusive; we hypothesize anxiety levels in residents are high, since residency programs are developed in community hospitals that lack material andhuman resources. The aim of this study is to determine the levels of anxiety in medical residents of diferent specialtes using the State Trait-AnxietyInventary (STAI).Methods: An electronic poll with STAI was administered to medical residents of diferent specialtes of a tertary referral hospital.Results: We received 132 questonnaires for analysis. Most of the respondents are men (59%), single (83%), without dependents (79%), belong tosurgical or internal medicine residency (54%), work more than 80 hours per week (85%) and travel less than an hour to get to the hospital (67%). Theaverage level of state anxiety of the residents was 46.94 points, while the average level of trait anxiety was 42.77 points. Thirty fve percent of theresidents have medium anxiety levels and 59% high anxiety levels at the tme they answered the inventory; and 56% have medium anxiety levels and37% have high anxiety levels as a trait. We did not found a statstcal diference in anxiety levels based on gender, marital status, and type of residency,number of dependents or number of hours spent in trafc. The only variable that was associated with anxiety was the amount of work hours per week.Conclusions: Most of the residents have medium-high levels of anxiety; the only variable associated with anxiety levels was the amount of work hoursper week
Assuntos
Humanos , Esgotamento Profissional/diagnóstico , Ansiedade/diagnóstico , Internato e ResidênciaRESUMO
BACKGROUND: Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. METHODS: Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. RESULTS: Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95% confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. CONCLUSION: Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2.
Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Estudos de Casos e Controles , Feminino , Variação Genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 5 de Fator de Crescimento de Fibroblastos/genéticaRESUMO
The effectiveness of clorazepate dipotassium combined with fluoxetine and a behaviour modification programme for the treatment of anxiety disorders in dogs was investigated. Forty dogs with anxiety disorders were initially enrolled and 36 dogs completed the trial. Dogs were classified into two behavioural categories (anxious dogs with aggression and anxious dogs without aggression) according to their presenting complaints, and were also subdivided into males, females, juveniles and adults. The dog owners were provided with a behaviour modification plan for their dogs to be commenced in the first week of therapy. Clorazepate dipotassium was administered PO at 1.0 mg/kg every 24 h for 4 weeks, and fluoxetine was administered PO at 1.0 mg/kg every 24 h for 10 weeks. Therapy with both drugs was initiated simultaneously. Improvement was reported in 25/36 dogs. Significant differences in treatment effects were observed between anxious dogs with aggression and anxious dogs without aggression (P<0.05). Positive correlations between owner compliance with the treatment plan and reported improvement achieved during three periods of study were also noted.
Assuntos
Transtornos de Ansiedade/terapia , Terapia Comportamental , Clorazepato Dipotássico/uso terapêutico , Doenças do Cão/terapia , Fluoxetina/uso terapêutico , Agressão/efeitos dos fármacos , Animais , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Antidepressivos de Segunda Geração/farmacologia , Antidepressivos de Segunda Geração/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Clorazepato Dipotássico/farmacologia , Doenças do Cão/tratamento farmacológico , Cães , Quimioterapia Combinada , Feminino , Fluoxetina/farmacologia , Masculino , EspanhaRESUMO
Objetivo. Contribuir con la caracterización estadística y genotípica (media, media del error estándar, varianza y heredabilidad) de la Longitud Total (LT) y Longitud Altura del Lomo (LAL), y plantear una estrategia de selección para mejorar la calidad de la semilla de reproductores de tilapia roja Oreochromis sp. Materiales y métodos. El proyecto se realizó en la Granja Experimental y de Producción Piscícola (PCJIC), a un Km del municipio de San Jerónimo, distante 61 Km al Occidente de Medellín (Antioquia). Se conformaron tres grupos de cruzamientos, cada uno en proporción de 3 hembras por 1 macho así: un cruce Hembras Blancas (HB) x Macho Rojo (MR) y dos cruces Hembras Blancas (HB) x Macho Blanco (MB). Las progenies fueron medidas a los 60 días post eclosión, teniendo en cuenta los supuestos estadísticos. Resultados. El ANOVA mostró que las progenies difieren significativamente (p<0.001) para ambas variables continuas. La LT fue mayor para la progenie del cruzamiento HBxMB sin reversión (8.04±1.04cm) y LAL fue mayor para la progenie HBxMR (2.33±0.44cm). La correlación pareada entre las variables fue altamente significativa (r≥0.79, p<0.001). Las heredabilidades fueron 0.59 (LT) y 0.64 (LAL). Los porcentajes de manchas en las progenies fueron HBxMR (34%) y HBxMB no revertida (66%). Conclusiones. La progenie del Grupo 1 HBxMR tuvo los reproductores para una mejor selección por conformación, por lo que se sugiere aumentar el número de animales con mayor LAL. También, considerar la menor cantidad de manchas oscuras y realizar un manejo de reproductores por grupos independientes para selección masal.
Objective. Contribute to the statistical and genotypic characterization (mean, standard error, variance and heritability) of the Total Length (LT) and Height (LAL), and suggest a selection strategy to improve seed quality in broodstock of red tilapia Oreochromis sp. Materials and methods. The project was conducted in the Experimental and Production Fish Farm (PCJIC), one Km from the town of San Jerónimo, 61 Km to the west of Medellín (Antioquia). Three mating groups were formed, each in proportion of 3 females and 1 male: a mating group of White Females (HB) x Red Male (MR) and two mating groups White Females (HB) x White Male (MB). The offspring were measured at 60 days post hatching, taking into account statistical assumptions. Results. The ANOVA showed that offspring differ significantly (p<0.001) for both continuous variables. The LT was greater for the offspring of HBxMB without reversion (8.04±1.04cm) and LAL was higher for the HBxMR offspring (2.33±0.44cm). The paired correlation between variables was highly significant (r≥0.79, p<0.001). Heritability were 0.59 (LT) and 0.64 (LAL). The dark spot percentages of the offspring were HBxMR (34%) and non-reversed HBxMB (66%). Conclusions. The progeny of Group 1 HBxHR had the better broodstocks for selection by conformation. It is suggested that the number of animals with greater LAL is increased. Additionally, it is important to consider the minor amount of dark spots in broodstock management by independent groups for mass selection.
Assuntos
Peixes , Melhoramento Genético , HereditariedadeRESUMO
Estrogen receptor (ER) positive primary breast cancers have a wide range of clinical outcomes. Prediction of the likely course of the disease aids treatment decision-making. In the translational arm of the ATAC (anastrozole or tamoxifen alone or combined) trial (TransATAC) we have assessed individual and multiparameter biomarkers for their prediction of overall and distant recurrence. None of the biomarkers identified differential benefit for anastrozole versus tamoxifen. Each of ER, PgR, HER2 and Ki67 was associated with risk of recurrence. A combination of these to create a single predictor IHC4 was as informative as the 21-gene recurrence score (RS). Integration of each of these molecular profiles with classical clinicopathologic variables provided the most accurate prediction of outcome.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Inibidores da Aromatase/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/diagnóstico , Nitrilas/uso terapêutico , Tamoxifeno/uso terapêutico , Triazóis/uso terapêutico , Algoritmos , Anastrozol , Quimioterapia Adjuvante , Feminino , Humanos , Antígeno Ki-67/genética , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/genética , Resultado do TratamentoRESUMO
The lethal and sublethal effects of the ecdysone agonist methoxyfenozide on the fall armyworm, Spodoptera frugiperda (J. E. Smith), were investigated by feeding a methoxyfenozide-treated diet to fifth instars until pupation in doses corresponding to the LC10 and LC25 for the compound. Larval mortality reached 8% and 26% in the low and high concentration groups, respectively, on the seventh day of the experiment. A progressive larval mortality of 12% for the LC10 and 60% for the LC25 was observed before pupation. Treated larvae exhibited lower pupal weights, higher pupal mortality, presence of deformed pupae, and more deformed adults than untreated larvae. The incorporation of methoxyfenozide into the diet had a significant effect on the timing of larval development. The development period for males and females was about seven days longer than the controls for both concentrations tested. In contrast, the compound affected neither pupae nor adult longevity. Finally, S. frugiperda adults that resulted from fifth instars treated with methoxyfenozide were not affected in their mean cumulative number of eggs laid per female (fecundity), nor percentages of eggs hatched (fertility), or the sex ratio. Our results suggest that the combination of lethal and sublethal effects of methoxyfenozide may have important implications for the population dynamics of the fall armyworm.
Assuntos
Hidrazinas/farmacologia , Hormônios Juvenis/farmacologia , Spodoptera/efeitos dos fármacos , Spodoptera/fisiologia , Animais , Feminino , Fertilidade/efeitos dos fármacos , Hidrazinas/toxicidade , Hormônios Juvenis/toxicidade , Larva/efeitos dos fármacos , Masculino , Controle de Pragas , Spodoptera/crescimento & desenvolvimentoRESUMO
The lethal and sublethal effects of the ecdysone agonist methoxyfenozide on the fall armyworm, Spodoptera frugiperda (J. E. Smith), were investigated by feeding a methoxyfenozide-treated diet to fifth instars until pupation in doses corresponding to the LC10 and LC25 for the compound. Larval mortality reached 8 percent and 26 percent in the low and high concentration groups, respectively, on the seventh day of the experiment. A progressive larval mortality of 12 percent for the LC10 and 60 percent for the LC25 was observed before pupation. Treated larvae exhibited lower pupal weights, higher pupal mortality, presence of deformed pupae, and more deformed adults than untreated larvae. The incorporation of methoxyfenozide into the diet had a significant effect on the timing of larval development. The development period for males and females was about seven days longer than the controls for both concentrations tested. In contrast, the compound affected neither pupae nor adult longevity. Finally, S. frugiperda adults that resulted from fifth instars treated with methoxyfenozide were not affected in their mean cumulative number of eggs laid per female (fecundity), nor percentages of eggs hatched (fertility), or the sex ratio. Our results suggest that the combination of lethal and sublethal effects of methoxyfenozide may have important implications for the population dynamics of the fall armyworm.
Assuntos
Animais , Feminino , Masculino , Hidrazinas/farmacologia , Hormônios Juvenis/farmacologia , Spodoptera/efeitos dos fármacos , Spodoptera/fisiologia , Fertilidade/efeitos dos fármacos , Hidrazinas/toxicidade , Hormônios Juvenis/toxicidade , Larva/efeitos dos fármacos , Controle de Pragas , Spodoptera/crescimento & desenvolvimentoRESUMO
In Argentina, transgenic soybean crop (Roundup Ready, RR) has undergone a major expansion over the last 15 years, with the consequent increase of glyphosate applications, a broad-spectrum and post emergence herbicide. Soybean crops are inhabited by several arthropods. Eriopis connexa Germar (Coleoptera: Coccinelidae) is a predator associated to soybean soft-bodies pest and have a Neotropical distribution. Nowadays, it is being considered a potentially biological control agent in South America. The objectives of this work were to evaluate the side-effects of glyphosate on larvae (third instar) and adults of this predator. Commercial compound and the maximum registered concentrations for field use were employed: GlifoGlex 48 (48% glyphosate, 192 mg a.i./litre, Gleba Argentina S.A.). The exposure was by ingestion through the treated prey (Rophalosiphum padi) or by drinking treated water during 48 h for treatment of the adult. The herbicide solutions were prepared using distilled water as solvent. The bioassays were carried out in the laboratory under controlled conditions: 23 +/- 0.5 degrees C, 75 +/- 5% RH and 16:8 (L:D) of photoperiod. Development time, weight of pupae, adult emergence, pre-oviposition period, fecundity and fertility were evaluated as endpoints. Larvae from glyphosate treatment molted earlier than controls. In addition, the weight of pupae, longevity, fecundity and fertility were drastically reduced in treated organisms. The reductions were more drastic when the treatments were performed at the third larval stage than as adult. The reproduction capacity of the predator was the most affected parameter and could be related to a hormonal disruption by glyphosate in the treated organisms. This work can confirm the deleterious effects of this herbicide on beneficial organisms. Also, it agrees with prior studies carried out on other predators associated to soybean pest, such as Chrysoperla externa (Neuroptera: Chrysopidae) and Alpaida veniliae (Araneae: Araneidae).
Assuntos
Besouros/efeitos dos fármacos , Glicina/análogos & derivados , Herbicidas/toxicidade , Animais , Glicina/toxicidade , Larva/efeitos dos fármacos , Óvulo/efeitos dos fármacos , Controle Biológico de Vetores , Plantas Geneticamente Modificadas , Glycine max/efeitos dos fármacos , Glycine max/genética , GlifosatoRESUMO
The integrated pest management (IPM) premises claim for a joint use of beneficial organisms (parasitoids and predators) and selective pesticides. Botanical pesticides are being considered as selective pesticides. During the last 20 years of the 20th century, the plant family Meliaceae was identified as a promising source of compounds with insect-control properties. The Chinaberry tree, Melia azedarach L., is a deciduous tree native to Persia, India, and China, but has been cultivated in many countries including Africa, Australia, and the Americas. It is a source of tetranortriterpenoid compounds called meliatoxins, which have similar structures and insecticidal activities compared to azadirachtin. Eriopis connexa Germar (Coleoptera: Coccinelidae) is a native predator from the Neotropical Region. It is a beneficial organism associated to several agro-ecosystems, feeding on soft-bodies pest such as aphids, whiteflies and thrips. In horticultural crops, it has been observed to feed on worldwide important pest such as Bemisia tabaci Gennadius (Heteroptera: Aleyrodeidae) and Myzus persicae L. (Heteroptera: Aphididae), both of them considered as virus vectors. The objectives of this work were to evaluate the side-effects of M. azaderach (Meliaceas) extract on eggs, larvae and adults of Eriopis connexa. Extracts from unripe fruits (1%, w/w, obtained by the CEPROCOR, Cordoba-Argentina) were employed for ecotoxicological bioassays. The exposure method was by immersion for eggs and by ingestion of drinking water for adults. The botanical extract solutions were prepared using distilled water as solvent and a tensioactive (Tween 20) for topical application. The bioassays were carried out in the laboratory under controlled conditions: 23 +/- 0.5 degrees C temperature, 75 +/- 5% RH and 16:8 (L:D) photoperiod. Hatching, development time, adult emergence, pre-oviposition period, fecundity and fertility were evaluated as endpoints. No detrimental effects were observed in treated organisms irrespective of the exposure way and development stage. According to these preliminary results, M. azaderach fruit extracts can be compatible with E. connexa for pest control. However, future studies should be addressed to conclude about its toxicity on beneficial organisms.