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1.
J Neurochem ; 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-36977628

RESUMO

AMP-activated protein kinase (AMPK) is a key sensor of energy balance playing important roles in the balancing of anabolic and catabolic activities. The high energy demands of the brain and its limited capacity to store energy indicate that AMPK may play a significant role in brain metabolism. Here, we activated AMPK in guinea pig cortical tissue slices, both directly with A769662 and PF 06409577 and indirectly with AICAR and metformin. We studied the resultant metabolism of [1-13 C]glucose and [1,2-13 C]acetate using NMR spectroscopy. We found distinct activator concentration-dependent effects on metabolism, which ranged from decreased metabolic pool sizes at EC50 activator concentrations with no expected stimulation in glycolytic flux to increased aerobic glycolysis and decreased pyruvate metabolism with certain activators. Further, activation with direct versus indirect activators produced distinct metabolic outcomes at both low (EC50 ) and higher (EC50 × 10) concentrations. Specific direct activation of ß1-containing AMPK isoforms with PF 06409577 resulted in increased Krebs cycle activity, restoring pyruvate metabolism while A769662 increased lactate and alanine production, as well as labelling of citrate and glutamine. These results reveal a complex metabolic response to AMPK activators in brain beyond increased aerobic glycolysis and indicate that further research is warranted into their concentration- and mechanism-dependent impact.

2.
Exp Appl Acarol ; 89(3-4): 447-460, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37052726

RESUMO

The cattle fever tick, Rhipicephalus (Boophilus) microplus, is the most economically important tick worldwide. Infestations with this tick can lead to direct damage and cattle mortality due to the transmission of potentially deadly pathogens. Management of this tick species has been focused on the use of synthetical acaricides; however, the emergence of acaricide resistance to single or multiple active ingredients has resulted in a need for novel acaricide compounds. Among potential avenues for the discovery of novel acaricides are plant-derived compounds. The efficacy of five organic compounds (nootkatone, Stop the Bites®, BioUD®, lavender oil, and cedarwood oil) was evaluated using larval immersion tests (LITs), repellency assays, and adult immersion tests (AITs). The results from the LITs indicate that three of the organic compounds (NootkaShield™, Stop the Bites, BioUD) led to significant mortalities at low concentrations (0.2, 0.02, and 0.08%, respectively). By comparison, lavender and cedar oil led to around 90% mortality at 10 and 1% concentrations, respectively. Similarly, NootkaShield, Stop the Bites, and BioUD had strong repellent properties with over 90% repellency at the two highest concentrations tested. Using the FAO 2004 guidelines, we evaluated the effectiveness of these organic compounds at reducing the fecundity of R. (B.) microplus and show that Nootkatone, Stop the Bites, and BioUD may significantly decrease tick populations (Drummond's index > 90% at concentrations of 5%), highlighting their potential as alternatives to synthetic acaricides for the control of cattle fever ticks.


Assuntos
Acaricidas , Doenças dos Bovinos , Ixodidae , Rhipicephalus , Infestações por Carrapato , Bovinos , Animais , Acaricidas/farmacologia , Infestações por Carrapato/veterinária , Larva , Doenças dos Bovinos/prevenção & controle
3.
Environ Monit Assess ; 195(5): 551, 2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37036575

RESUMO

This study compiles commonly available groundwater chemistry data from the Pearl Harbor Sole Source Aquifer (SSA), Hawai'i-O'ahu's primary drinking water source-and applies hierarchical clustering analysis (HCA), principal component analyses (PCA), piper diagrams, and box plots with geospatial analysis to better define groundwater regions and correlate groundwater chemistry in those regions with land use. Groundwater in this aquifer recharges and flows through chemically similar soil and rocks, such that anthropogenic activities are a primary influence on the chemical variability of the aquifer's differing regions. Our analyses link specific chemical species in groundwater to land use/cover categories: urban, agriculture, and natural and anthropogenically-induced saline water intrusion. To create distinct statistical groupings with different groundwater chemistry compositions, it was important that the suite of parameters used in the statistical analysis do not covary. In our case, Cl- covaried with several major ions; however, by including F-, alkalinity, and SiOx that do not covary with Cl- in the covariance matrix, we produced improved spatial grouping of HCA clusters and stronger affinities to land use designations. Results show that dominant groundwater chemistry changes with land use along flow paths. These results pertain to areas where groundwater flows from conservation land in high recharge areas of O'ahu's mountain ranges to urban and agricultural land use regions: groundwater retains its source characteristics until about 3-6 km into agricultural and urban zoned lands. Ultimately, this study outlines a simple method for water quality regulators to use groundwater chemistry to identify risks of target contaminants based on land use.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , Havaí , Monitoramento Ambiental/métodos , Poluentes Químicos da Água/análise , Água Subterrânea/química , Qualidade da Água
4.
Environ Monit Assess ; 195(11): 1265, 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37783813

RESUMO

Precipitation is the primary groundwater source for the Island of O'ahu, Hawai'i, USA, and is an important source of terrestrial nutrients. Since Pacific Islands are particularly vulnerable to the impacts of climate change, they are important venues for studying the controls on and fluctuations in precipitation chemistry. Spatial variations in some of the dissolved rainfall ions can also be of value as natural geochemical tracers in examining surface and groundwater flow. This study collected and chemically analyzed bulk precipitation from 20 sites across the Island of O'ahu approximately quarterly between April 2018 and August 2021. The new precipitation chemistry data were integrated with previously published precipitation data to characterize major ion composition and examine the atmospheric processes controlling inorganic ion deposition. Linear regression and multivariate analysis were used to quantify the relationships among major ions and to assess the impacts of various environmental and meteorological factors on precipitation chemistry. Ordinary kriging and inverse distance weighted interpolations were conducted to help visualize spatial variations in major ion deposition. The results clearly indicate that ocean sea spray is the primary driver of precipitation inorganic chemistry, with marine sea salt aerosols accounting for more than 90% of the measured ion load. However, they also show that various weather patterns and nutrient sources impact inorganic deposition. Most notably, upper atmospheric transport of Asian continental dust during Hawaiian wet seasons, Ca2+ from local sedimentary deposits, and anthropogenic K+ from agricultural activity appear to be substantial non-marine deposition sources. This study synthesizes data from multiple sources into the most spatially and topographically diverse precipitation collector network on O'ahu to date. The findings from this effort help establish a baseline for assessing future fluctuations in inorganic ion deposition and lay important groundwork for examining connections between precipitation and groundwater chemistry within the study area.


Assuntos
Monitoramento Ambiental , Água Subterrânea , Havaí , Estações do Ano , Tempo (Meteorologia)
5.
Ann Rheum Dis ; 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35914929

RESUMO

OBJECTIVES: Premature cardiovascular events in systemic lupus erythematosus (SLE) contribute to morbidity and mortality, with no effective preventive strategies described to date. Immune dysregulation and metabolic disturbances appear to play prominent roles in the induction of vascular disease in SLE. The peroxisome proliferator activated receptor-gamma agonist pioglitazone (PGZ suppresses vascular damage and immune dysregulation in murine lupus and improves endothelial dysfunction in other inflammatory diseases. We hypothesised that PGZ could improve vascular dysfunction and cardiometabolic parameters in SLE. METHODS: Eighty SLE subjects with mild to severe disease activity were randomised to a sequence of PGZ followed by placebo for 3 months, or vice versa, in a double-blind, cross-over design with a 2-month wash-out period. Primary endpoints were parameters of endothelial function and arterial inflammation, measured by multimodal assessments. Additional outcome measures of disease activity, neutrophil dysregulation, metabolic disturbances and gene expression studies were performed. RESULTS: Seventy-two subjects completed the study. PGZ was associated with a significant reduction in Cardio-Ankle Vascular Index (a measure of arterial stiffness) compared with placebo. Various metabolic parameters improved with PGZ, including insulin resistance and lipoprotein profiles. Circulating neutrophil extracellular trap levels also significantly decreased with PGZ compared with placebo. Most adverse events experienced while on PGZ were mild and resolved with reduction in PGZ dose. CONCLUSION: PGZ was well tolerated and induced significant improvement in vascular stiffness and cardiometabolic parameters in SLE. The results suggest that PGZ should be further explored as a modulator of cardiovascular disease risk in SLE. TRIAL REGISTRATION NUMBER: NCT02338999.

6.
Exp Appl Acarol ; 86(3): 431-441, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35235093

RESUMO

Following its eradication from the USA, the cattle fever tick, Rhipicephalus (Boophilus) microplus (Canestrini), a vector of bovine babesiosis, has made episodic incursions into, and sometimes beyond, an established barrier zone separating tick-free from endemic areas. In large part the incursions involve hosting and transport by wild ungulates, particularly deer and antelope. One approach to disinfest ticks from wild hosts is with food baits medicated to stop parasites. The approach has had mixed success due to factors that have been previously identified with supplemental feeding of wildlife especially competition for the bait, social dominance behavior, and the availability of alternative food sources. Given that not all of the target hosts will intake a therapeutic dose of the medication (ivermectin) at all seasons of the year, an open question is whether the approach is efficacious as a stand-alone treatment or even as part of an integrated program. As detailed in the present study an intensive effort was successful in eradicating a local outbreak of fever ticks.


Assuntos
Babesiose , Doenças dos Bovinos , Cervos , Ixodidae , Rhipicephalus , Infestações por Carrapato , Animais , Bovinos , Doenças dos Bovinos/parasitologia , Cervos/parasitologia , Ivermectina/uso terapêutico , Infestações por Carrapato/tratamento farmacológico , Infestações por Carrapato/prevenção & controle , Infestações por Carrapato/veterinária , Zea mays
7.
Biopolymers ; 112(4): e23409, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33207389

RESUMO

Dimers of 9-aminoacridine linked via the 9-amino group with polymethylene chains, termed diacridines, are known to bisintercalate into DNA when the linker comprises 6 or more methylene units. There are no literature reports of crystal or NMR solution structures for bisintercalated diacridine-DNA complexes, and the issue of the structure of the C6 ([CH2 ]n linker where n = 6) diacridine complex remains unresolved. Previously, based on simple geometric considerations, it was proposed that C6 diacridine could only span a single base pair, which requires that its bifunctional reaction violates the widely-observed "neighbor exclusion principle" where bound intercalators are separated by at least 2 base pairs. Here we have explored the structure of diacridine-DNA complexes using unrestrained molecular dynamics in explicit solvent using the parmbsc0 forcefield in AMBER14. We studied the C4 to C8 dimers, intercalated via both the minor and major DNA grooves, to a variety of nucleotide sequences. We find that C6, C7, and C8 diacridine are able to form 2 base pair bisintercalated complexes from either groove, whereas the C4 and C5 homologues cannot. We conclude that C6 diacridine does have the capacity to bisintercalate without violating neighbor exclusion, and that the previous proposed binding model needs revision.


Assuntos
Aminacrina/química , Aminacrina/metabolismo , DNA/química , DNA/metabolismo , Pareamento de Bases , Substâncias Intercalantes/química , Simulação de Dinâmica Molecular , Conformação de Ácido Nucleico , Relação Estrutura-Atividade
8.
J Mol Recognit ; 33(8): e2843, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32253794

RESUMO

Structure activity relationships for tricyclic-carboxamide topoisomerase II poisons indicate that cytotoxicity is enhanced by the presence of methyl, and other, groups in the position peri to the carboxamide. Linked dimers of phenazine-1-carboxamides are potent cytotoxins and one phenazine dimer, MLN944 (alternatively XR5944), has been in clinical trial. MLN944 is a template inhibitor of transcription, whereas corresponding monomers are not. Nevertheless, its cytotoxic potency is also diminished by removal of its peri methyl groups. Here, we describe NMR and molecular dynamic studies of the interaction of desmethyl MLN944 with d(ATGCAT)2 , d(TATGCATA)2 , and d(TACGCGTA)2 to investigate the influence of the nine-methyl group on the structure of MLN944 complexes. As with MLN944, the carboxamide group hydrogen bonds to the phenazine ring nitrogen, the ligand sandwiches the central GC base pairs in the major groove, and the protonated linker amines hydrogen bond primarily to the O6 atom of the guanines. Molecular dynamics studies reveal that the linker exists in multiple conformations, none of which produce an ideal set of hydrogen bonds. In distinction, however, the carboxamide-to-phenazine ring nitrogen hydrogen bond is weaker, the overall helix winding is less and the NMR resonances are broader in the desmethyl complexes. Exchange between free and complexed DNA, quantified using two-dimensional NOESY spectra, is faster for the desmethyl MLN944 complexes than for MLN944 complexes. Overall, the data suggest that desmethyl MLN944 DNA complexes are "looser" and more unwound at the binding site, leading to faster dissociation rates, which could account for the diminished efficacy of the desmethyl analog.


Assuntos
DNA/química , Simulação de Dinâmica Molecular , Fenazinas/química , Antineoplásicos , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Conformação de Ácido Nucleico
9.
Ann Entomol Soc Am ; 113(6): 425-438, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33244354

RESUMO

Questing is a host-seeking behavior in which ticks ascend plants, extend their front legs, and wait poised for a chance to attach to a passing host. Hard ticks are ectoparasites of terrestrial vertebrates and because some species vector disease, they are among the most medically important of arthropod pests. All ixodid ticks require blood to survive and reproduce with the number of blood-hosts needed to complete their life cycle varying among species. The vast majority are three-host ticks requiring a different host for each developmental stage: larva, nymph, and adult. A few, including some of the most economically important species, are one-host ticks, that quest only in the larval stage. Questing is a rate-limiting behavior critical to tick survival and disease transmission. For the off-host larval stage, survival is highly dependent on ecological and physiological factors. Yet, off-host larval ecophysiology is often overlooked for the more obvious adult and nymphal tick-host interactions. This review summarizes the literature on ixodid larval questing with emphasis on how specific biotic and abiotic factors affect off-host survival.

10.
J Am Chem Soc ; 140(41): 13392-13406, 2018 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-30230329

RESUMO

Natural biopolymers, such as DNA and proteins, have uniform microstructures with defined molecular weight, precise monomer sequence, and stereoregularity along the polymer main chain that affords them unique biological functions. To reproduce such structurally perfect polymers and understand the mechanism of specific functions through chemical approaches, researchers have proposed using synthetic polymers as an alternative due to their broad chemical diversity and relatively simple manipulation. Herein, we report a new methodology to prepare sequence-controlled and stereospecific oligomers using alternating radical chain growth and sequential photoinduced RAFT single unit monomer insertion (photo-RAFT SUMI). Two families of cyclic monomers, the indenes and the N-substituted maleimides, can be alternatively inserted into RAFT agents, one unit at a time, allowing the monomer sequence to be controlled through sequential and alternating monomer addition. Importantly, the stereochemistry of cyclic monomer insertion into the RAFT agents is found to be trans-selective along the main chains due to steric hindrance from the repeating monomer units. All investigated cyclic monomers provide such trans-selectivity, but analogous acyclic monomers give a mixed cis- and trans-insertion.


Assuntos
Indenos/química , Maleimidas/química , Polímeros/síntese química , Tionas/química , Técnicas de Química Sintética/métodos , Luz , Polimerização , Estereoisomerismo , Tionas/efeitos da radiação
11.
Clin J Sport Med ; 28(1): 56-63, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28085687

RESUMO

OBJECTIVES: We quantified the length of recovery time by week in a cohort of pediatric sports-related concussion patients treated at concussion clinics, and examined patient and injury characteristics associated with prolonged recovery. DESIGN: A retrospective, cohort design. SETTING: Seven concussion clinics at a Midwest children's hospital. PATIENTS: Patients aged 10 to 17 years with a diagnosed sports-related concussion presenting to the clinic within 30 days of injury. MAIN OUTCOME MEASURES: Length of recovery by week. METHODS: Unadjusted and adjusted multinomial logistic regression analyses were used to model the effect of patient and injury characteristics on length of recovery by week. RESULTS: Median length of recovery was 17 days. Only 16.3% (299/1840) of patients recovered within one week, whereas 26.4% took longer than four weeks to recover. By 2 months postinjury, 6.7% of patients were still experiencing symptoms. Higher symptom scores at injury and initial visit were significantly associated with prolonged symptoms by week. Patients who presented to the clinic more than 2 weeks postinjury or who had 2 or more previous concussions showed increased risk for prolonged recovery. Females were at greater risk for prolonged recovery than males (odds ratio = 2.08, 95% confidence interval = 1.49-2.89). Age was not significantly associated with recovery length. CONCLUSIONS: High symptom scores at injury and initial visit, time to initial clinical presentation, presence of 2 or more previous concussions, and female sex are associated with prolonged concussion recovery. Further research should aim to establish objective measures of recovery, accounting for treatment received during the recovery. CLINICAL RELEVANCE: The median length of recovery is 17 days among pediatric sports-related concussion patients treated at concussion clinics. Only 16.3% of patients recovered within one week, whereas 26.4% took longer than 4 weeks to recover.


Assuntos
Traumatismos em Atletas/diagnóstico , Concussão Encefálica/diagnóstico , Recuperação de Função Fisiológica , Adolescente , Criança , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Índices de Gravidade do Trauma
12.
Neurochem Res ; 42(6): 1710-1723, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28316020

RESUMO

The ketone body, ß-hydroxybutyrate (ßOHB), is metabolised by the brain alongside the mandatory brain fuel glucose. To examine the extent and circumstances by which ßOHB can supplement glucose metabolism, we studied guinea pig cortical brain slices using increasing concentrations of [U-13C]D-ßOHB in conjunction with [1-13C]D-glucose under conditions of normo- and hypoglycaemia, as well as under high potassium (40 mmol/L K+) depolarization in normo- and hypoglycaemic conditions. The contribution of ßOHB to synthesis of GABA was also probed by inhibiting the synthesis of glutamine, a GABA precursor, with methionine sulfoximine (MSO). [U-13C]D-ßOHB at lower concentrations (0.25 and 1.25 mmol/L) stimulated mitochondrial metabolism, producing greater total incorporation of label into glutamate and GABA but did not have a similar effect in the cytosolic compartment where labelling of glutamine was reduced at 1.25 mmol/L [U-13C]D-ßOHB. At higher concentrations (2.5 mmol/L) [U-13C]D-ßOHB inhibited metabolism of [1-13C]D-glucose, and reduced total label incorporation and total metabolite pools. When glucose levels were reduced, ßOHB was able to partially restore the loss of glutamate and GABA caused by hypoglycaemia, but was not able to supplement levels of lactate, glutamine or alanine or to prevent the increase in aspartate. Under depolarizing conditions glucose was the preferred substrate over ßOHB, even in hypoglycaemic conditions where comparatively less ßOHB was incorporated except into aspartate isotopomers. Inhibition of glutamine synthesis with MSO had no significant effect on incorporation of label from [U-13C]D-ßOHB into GABA C2,1 indicating that the majority of this GABA was synthesized in GABAergic neurons from [U-13C]D-ßOHB rather than from Gln C4,5 imported from astrocytes.


Assuntos
Ácido 3-Hidroxibutírico/metabolismo , Ácido 3-Hidroxibutírico/farmacologia , Glucose/metabolismo , Mitocôndrias/metabolismo , Neurônios/metabolismo , Animais , Relação Dose-Resposta a Droga , Glutamina/metabolismo , Cobaias , Masculino , Mitocôndrias/efeitos dos fármacos , Neurônios/efeitos dos fármacos
13.
Microbiology (Reading) ; 162(8): 1388-1397, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27339421

RESUMO

Campylobacter concisus is a member of the oral microbiota that has been associated with the development of inflammatory bowel diseases. However, the role of the bacterium in disease aetiology remains poorly understood. Here, we examine optimal conditions for the growth of C. concisus, and the pathogenic potential of this bacterium in human gastrointestinal cells from the upper tract. Further, the presence of C. concisus in the lower tract of Crohn's disease (CD) patients undergoing therapy is observed, and the associations of C. concisus with the abundance of other microbial taxa and compounds they produce are evaluated. C. concisus strains had the ability to tolerate moderate levels of acidity, adhere to and invade esophageal and gastric cells; however, these properties did not correlate with their pathogenic potential in intestinal cells. The presence of the bacterium in the lower gut of CD patients was associated with an increased relative abundance of Faecalibacterium and Lachnospiraceae incertae sedis. Short chain fatty acids that can be produced by these microbial species did not appear to be responsible for this association. However, we identified genetic similarity between C. concisus and Firmicutes, specifically within aspartate and glutamate racemases. The potential pathogenesis of C. concisus in the upper gastrointestinal tract, and the responsiveness of the bacterium to therapy in a subset of CD patients warrant further investigation into whether this bacterium has a causal role in disease or its presence is incidental.


Assuntos
Sangue/microbiologia , Campylobacter/classificação , Campylobacter/patogenicidade , Doença de Crohn/microbiologia , Ácidos Graxos Voláteis/metabolismo , Firmicutes/classificação , Trato Gastrointestinal/microbiologia , Aderência Bacteriana/fisiologia , Campylobacter/genética , Campylobacter/metabolismo , Infecções por Campylobacter/microbiologia , Células Cultivadas , Clostridiales/isolamento & purificação , Faecalibacterium/isolamento & purificação , Firmicutes/genética , Trato Gastrointestinal/citologia , Humanos
14.
Magn Reson Chem ; 54(6): 423-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25287592

RESUMO

In order to understand reaction outcomes in ionic liquids, it is crucial to be able to follow the progress of these reactions. This review highlights the advantages of NMR spectroscopy over other analytical techniques in following reaction progress in ionic liquids, particularly addressing the practical aspects of the methodology and highlighting the range of processes that can be readily followed. Copyright © 2014 John Wiley & Sons, Ltd.

15.
J Neurosci Res ; 93(7): 1147-56, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25677687

RESUMO

Silent information regulators (SIRTs) have been shown to deacetylate a range of metabolic enzymes, including those in glycolysis and the Krebs cycle, and thus alter their activity. SIRTs require NAD(+) for their activity, linking cellular energy status to enzyme activity. To examine the impact of SIRT1 modulation on oxidative metabolism, this study tests the effect of ligands that are either SIRT-activating compounds (resveratrol and SRT1720) or SIRT inhibitors (EX527) on the metabolism of (13)C-enriched substrates by guinea pig brain cortical tissue slices with (13)C and (1)H nuclear magnetic resonance spectroscopy. Resveratrol increased lactate labeling but decreased incorporation of (13)C into Krebs cycle intermediates, consistent with effects on AMPK and inhibition of the F0/F1-ATPase. By testing with resveratrol that was directly applied to astrocytes with a Seahorse analyzer, increased glycolytic shift and increased mitochondrial proton leak resulting from interactions of resveratrol with the mitochondrial electron transport chain were revealed. SRT1720, by contrast, stimulated incorporation of (13)C into Krebs cycle intermediates and reduced incorporation into lactate, although the inhibitor EX527 paradoxically also increased Krebs cycle (13)C incorporation. In summary, the various SIRT1 modulators show distinct acute effects on oxidative metabolism. The strong effects of resveratrol on the mitochondrial respiratory chain and on glycolysis suggest that caution should be used in attempts to increase bioavailability of this compound in the CNS.


Assuntos
Antioxidantes/farmacologia , Encéfalo , Ácido Láctico/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estilbenos/farmacologia , Animais , Área Sob a Curva , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/ultraestrutura , Carbazóis/farmacologia , Isótopos de Carbono/metabolismo , Relação Dose-Resposta a Droga , Feminino , Cobaias , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Imageamento por Ressonância Magnética , Masculino , Estresse Oxidativo/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Resveratrol , Sirtuína 1/antagonistas & inibidores , Sirtuína 1/metabolismo
16.
Org Biomol Chem ; 13(34): 9035-41, 2015 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-26220565

RESUMO

A series of aromatic hydrocarbons were investigated so as to compare the reactivity of corannulene with planar aromatic hydrocarbons. Corannulene was found to be more reactive than benzene, naphthalene and triphenylene to Friedel-Crafts acylation whilst electrophilic aromatic bromination was also used to confirm that triphenylene was less reactive than corannulene and that pyrene, perylene and acenaphthene were more so. The stabilisation of a neighbouring carbocation by the various aromatic systems was investigated through consideration of the rates of methanolysis of a series of benzylic alcohols. The reactivity series was found to parallel that observed for the electrophilic aromatic substitutions and both series are supported by computational studies. As such, a reactivity scale was devised that showed that corannulene was less reactive than would be expected for an aromatic planar species of similar pi electron count.

17.
J Econ Entomol ; 108(3): 1324-36, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26470261

RESUMO

Anastrepha ludens (Loew) (Diptera: Tephritidae), the Mexican fruit fly, is a major pest of citrus and mango. It has a wide distribution in Mexico and Central America, with infestations occurring in Texas, California, and Florida with origins believed to have been centered in northeastern Mexico. This research evaluates the utility of a sequence-based approach for two mitochondrial (COI and ND6) gene regions. We use these markers to examine genetic diversity, estimate population structure, and identify diagnostic information for A. ludens populations. We analyzed 543 individuals from 67 geographic collections and found one predominant haplotype occurring in the majority of specimens. We observed 68 haplotypes in all and see differences among haplotypes belonging to northern and southern collections. Mexico haplotypes differ by few bases possibly as a result of a recent bottleneck event. In contrast to the hypothesis suggesting northeastern Mexico as the origin of this species, we see that specimens from two southern collections show high genetic variability delineating three mitochondrial groups. These data suggest that Central America is the origin for A. ludens. We show that COI and ND6 are useful for phylogeographic studies of A. ludens.


Assuntos
Variação Genética , Tephritidae/genética , Animais , América Central , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Genoma Mitocondrial , Haplótipos , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Larva/crescimento & desenvolvimento , Larva/metabolismo , México , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Dados de Sequência Molecular , Filogenia , Filogeografia , Análise de Sequência de DNA , Tephritidae/crescimento & desenvolvimento , Tephritidae/metabolismo
18.
Biopolymers ; 101(11): 1099-113, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24898663

RESUMO

MLN 944 is a bisintercalating DNA-binding antitumor agent known to be a template inhibitor of transcription. Previous (1) H NMR studies of its d(ATGCAT)2 complex concluded that its phenazine chromophores are protonated. However, we find that this is not so, which has important consequences for the charged state of the ligand, for the orientation of its 1-carboxamide group in the complex, and for the details of the interaction of its protonated interchromophore linker with the DNA base pairs. Here, we report a corrected solution structure of the MLN 944-d(ATGCAT)2 complex, and extend the study to complexes with d(TATGCATA)2 , and d(TACGCGTA)2 , using a variety of (1) H and (31) P NMR methods and molecular dynamics simulations employing the AMBER 12 force field. We find that for all three complexes MLN 944 binds as a dication, in which the chromophores are uncharged, in the DNA major groove spanning the central 2 GC base pairs in a manner that maintains the dyad symmetry of the DNA. The carboxamide group lies in the plane of the chromophore, its NH making hydrogen bonding interactions with the phenazine N10 nitrogen, and the protonated linkers form hydrogen bonds with the O6 atom of guanine. The dynamics simulations reveal extensive solvent interactions involving the linker amines, the carboxamide group, and the DNA bases.


Assuntos
DNA/química , Fenazinas/química , Espectroscopia de Ressonância Magnética , Simulação de Dinâmica Molecular , Soluções , Termodinâmica
19.
J Econ Entomol ; 107(2): 591-600, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24772538

RESUMO

Early research investigating attractants for the Mexican fruit fly, Anastrepha ludens Loew, during the 1930s indicated that fermentation products were effective attractants for Mexican fruit flies and other tropical Tephritidae, but that attraction to fruit components was only of academic interest. Tests reported here were carried out on populations of Mexican fruit flies from 2004 to 2011. Trapping experiments carried out at sites in the states Nuevo Leon and San Luis Potosi compared grape juice, reconstituted grape concentrate and powdered grape mixes, and torula yeast extract in orchards at each site. The Nuevo Leon orchard was mixed with alternate rows of pears and surrounded by alternate hosts. The San Luis Potosi site was surrounded by other orange orchards or nonhosts. Each test was run for at least 10 mo and included highest and lowest trapping periods. Results showed that grape juice captured the most total flies and had the fewest samples with zero flies. However, in the series of experiments, each product had the most captures in at least one experiment. Hydrolyzed torula was superior in one of the six experiments. In five of the tests, polyethylene glycol was tested as an additive to the grape products but never improved capture rate compared with the product without the additive. These results indicate that grape juice is superior to grape concentrate or powder and grape juice is at least equal to torula yeast hydrolysate for trapping pest populations of Mexican fruit flies in commercial citrus orchards.


Assuntos
Cryptococcus/química , Controle de Insetos/métodos , Feromônios/farmacologia , Tephritidae/efeitos dos fármacos , Vitis/química , Animais , Feminino , Pyrus/crescimento & desenvolvimento , Estações do Ano , Tephritidae/fisiologia
20.
Syst Parasitol ; 89(3): 247-52, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25301513

RESUMO

A new nematode, Tripius gyraloura n. sp., is described from the arundo gall midge, Lasioptera donacis Coutin (Diptera: Cecidomyiidae). This gall midge is being considered as a biological control agent for use in North America against the introduced giant reed Arundo donax (L.) (Poaceae: Cyperales). Thus the present study was initiated to investigate a nematode parasite that was unknown at the time studies with L. donacis were initiated. The new species has a rapid development in the fly host and the mature parasitic female nematodes evert their uterine cells in the hosts' hemolymph. Because large numbers of nematodes sterilise the host, eradication of the parasite from laboratory colonies of the midge may be necessary before populations of the fly are released.


Assuntos
Dípteros/parasitologia , Nematoides/classificação , Nematoides/fisiologia , Animais , Feminino , Masculino , Nematoides/citologia , Especificidade da Espécie
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