To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Essential oils (EOs) are considered a new class of ecological products aimed at the control of insects for industrial and domestic use; however, there still is a lack of studies involving the control of fleas. Ctenocephalides felis felis, the most observed parasite in dogs and cats, is associated with several diseases. The aim of this study was to evaluate the in vitro activity, the establishment of LC50 and toxicity of EOs from Alpinia zerumbet (Pers.) B. L. Burtt & R. M. Sm, Cinnamomum spp., Laurus nobilis L., Mentha spicata L., Ocimum gratissimum L. and Cymbopogon nardus (L.) Rendle against immature stages and adults of C. felis felis. Bioassay results suggest that the method of evaluation was able to perform a pre-screening of the activity of several EOs, including the discriminatory evaluation of flea stages by their LC50. Ocimum gratissimum EO was the most effective in the in vitro assays against all flea stages, presenting adulticide (LC50 = 5.85 μg cm−2), ovicidal (LC50 = 1.79 μg cm−2) and larvicidal (LC50 = 1.21 μg cm−2) mortality at low doses. It also presented an excellent profile in a toxicological eukaryotic model. These findings may support studies involving the development of non-toxic products for the control of fleas in dogs and cats.
Considering a potential exercise-drug interaction, we investigated whether exercise training could improve the efficacy of specific antiparasitic chemotherapy in a rodent model of Chagas disease. Wistar rats were randomized into five groups: sedentary and uninfected (CT); sedentary and infected (SI); sedentary, infected and treated (SIT); trained and infected (TI); trained, infected and treated (TIT). After 9-weeks running training, the animals were infected with T. cruzi and followed up for 4 weeks, receiving 100 mg kg−1 day−1 benznidazole. No evidence of myocarditis was observed in CT animals. TI animals exhibited reduced parasitemia, myocarditis, and reactive tissue damage compared to SI animals, in addition to increased IFN-γ, IL-4, IL-10, heart non-protein antioxidant (NPA) levels and glutathione-s transferase activity (P < 0.05). The CT, SIT and TIT groups presented similar reductions in parasitemia, cytokines (IFN-γ, TNF-α, IL-4, IL-10, IL-17 and MCP-1), inflammatory infiltrate, oxidative heart damage and antioxidant enzymes activity compared to SI and TI animals, as well as reduced heart microstructural remodeling (P < 0.05). By modulating heart inflammation and redox metabolism, exercise training exerts a protective effect against T. cruzi infection in rats. However, the antiparasitic and cardioprotective effects of benznidazole chemotherapy are more pronounced, determining similar endpoints in sedentary and trained T. cruzi-infected rats.
In recent years, mobile robots have become increasingly frequent in daily life applications, such as cleaning, surveillance, support for the elderly and people with disabilities, as well as hazardous activities. However, a big challenge arises when the robotic system must perform a fully autonomous mission. The main problems of autonomous missions include path planning, localisation, and mapping. Thus, this research proposes a hybrid methodology for mobile robots on an autonomous mission involving an offline approach that uses the Direct-DRRT* algorithm and the artificial potential fields algorithm as the online planner. The experimental design covers three scenarios with an increasing degree of accuracy in respect of the real world. Additionally, an extensive evaluation of the proposed methodology is reported.
Metastable transitions in Langevin dynamics can exhibit rich behaviours that are markedly different from its overdamped limit. In addition to local alterations of the transition path geometry, more fundamental global changes may exist. For instance, when the dissipation is weak, heteroclinic connections that exist in the overdamped limit do not necessarily have a counterpart in the Langevin system, potentially leading to different transition rates. Furthermore, when the friction coefficient depends on the velocity, the overdamped limit no longer exists, but it is still possible to efficiently find instantons. The approach, we employed for these discoveries, was based on (i) a simple rewriting of the Freidlin–Wentzell action in terms of time-reversed dynamics and (ii) an adaptation of the string method, which was originally designed for gradient systems, to this specific non-gradient system.
Trichomonas vaginalis is responsible for the most common non-viral, sexually transmitted infection, human trichomoniasis, and is associated with an increased susceptibility to HIV. An escalation in resistance (2.5–10%) to the clinical drug, metronidazole (MTZ), has been detected and this compound also has adverse side-effects. Therefore, new treatment options are urgently required. Herein, we investigate the possible anti-T. vaginalis activity of 1,10-phenanthroline-5,6-dione (phendione) and its metal complexes, [Ag(phendione)2]ClO4 and [Cu(phendione)3](ClO4)2·4H2O. Minimum inhibitory concentration (MIC) against T. vaginalis ATCC 30236 and three fresh clinical isolates and mammalian cells were performed using serial dilution generating IC50 and CC50 values. Drugs combinations with MTZ were evaluated by chequerboard assay. A strong anti-T. vaginalis activity was found for all test compounds. IC50 values obtained for [Cu(phendione)3](ClO4)2·4H2O were similar or lower than those obtained for MTZ. In vitro assays with normal cells showed low cytotoxicity and [Cu(phendione)3](ClO4)2·4H2O presented a high selectivity index (SI) for fibroblasts (SI = 11.39) and erythrocytes (SI > 57.47). Chequerboard assay demonstrated that the combination of [Cu(phendione)3](ClO4)2·4H2O with MTZ leads to synergistic interaction, which suggests distinct mechanisms of action of the copper–phendione complex and avoiding the MTZ resistance pathways. Our results highlight the importance of phendione-based drugs as potential molecules of pharmaceutical interest.
The aim of this study was to optimize protocols for electroporation (EP) and polyfection (PLF) using polyethyleneimine (PEI) for pig sperm transfection and to determine which method was the most efficient. For EP standardization, different voltages, amounts and times of electric pulses were tested using propidium iodide (PI) as reporter. For PLF standardization, different concentrations of fluorescein isothiocyanate (FITC)-labelled PEI (PEI/FITC) were incubated with sperm for different periods of time. Flow cytometry was performed to evaluate the best protocol in terms of cell viability, including cytoplasmic membrane, acrosome, chromatin integrities and mitochondrial potential using the FITC probe, PI, acridine orange (AO) and JC1. Transfections with the plasmid pmhyGENIE-5 were carried out under optimum conditions for each procedure (EP: 500 volts, 500 μs and two pulses; PLF: PEI 0.5 mg/ml and incubation time 10 min). Transfection efficacy was assessed by fluorescence in situ hybridization (FISH). A lower transfection rate was observed for sperm in the control group (17.8%) compared with EP (36.7%), with PLF (76.8%) being the most efficient. These results suggest that the EP and PEI could be an efficient and low cost transfection method for swine sperm. Notably, treated cells showed higher plasmatic the membrane damage (PMD) and/or acrosome damage (AD) indexes, therefore the combination of this procedure with biotechniques that facilitate fecundation (i.e. in vitro fertilization or intracytoplasmic sperm injection) or even inclusion of antioxidant or anti-apoptotic drugs to improve spermatozoa viability would be important.
The anti-leishmania effects of HIV peptidase inhibitors (PIs) have been widely reported; however, the biochemical target and mode of action are still a matter of controversy in Leishmania parasites. Considering the possibility that HIV-PIs induce lipid accumulation in Leishmania amazonensis, we analysed the effects of lopinavir on the lipid metabolism of L. amazonensis promastigotes. To this end, parasites were treated with lopinavir at different concentrations and analysed by fluorescence microscopy and spectrofluorimetry, using a fluorescent lipophilic marker. Then, the cellular ultrastructure of treated and control parasites was analysed by transmission electron microscopy (TEM), and the lipid composition was investigated by thin-layer chromatography (TLC). Finally, the sterol content was assayed by gas chromatography–mass spectrometry (GC/MS). TEM analysis revealed an increased number of lipid inclusions in lopinavir-treated cells, which was accompanied by an increase in the lipophilic content, in a dose-dependent manner. TLC and GC–MS analysis revealed a marked increase of cholesterol-esters and cholesterol. In conclusion, lopinavir-induced lipid accumulation and affected lipid composition in L. amazonensis in a concentration–response manner. These data contribute to a better understanding of the possible mechanisms of action of this HIV-PI in L. amazonensis promastigotes. The concerted action of lopinavir on this and other cellular processes, such as the direct inhibition of an aspartyl peptidase, may be responsible for the arrested development of the parasite.
Considering the impact of coastal dynamics on the radiocarbon (14C) marine reservoir effect (MRE), upwelling has the potential of enhancing marine influence, usually 14C depleted. Freshwater input can contribute either to increased reservoir offsets, when dead carbon from rock weathering is available, but also towards an atmospheric 14C signal, when the presence of terrestrial organic matter from catchment prevails. An overview of the MRE studies based on shellmounds on the coast of Rio de Janeiro reveals a pattern of negative local corrections for Saquarema and Rio das Ostras but positive values for Cabo Frio island, suggesting the presence of cold upwelling waters in Cabo Frio at 1.6–1.2 cal kBP. New results for a shellmound on the Ilha Grande island, in the western portion of the Rio de Janeiro coast, revealed a negative value at about 3 ka. We discuss distribution of MRE values and temporal variability in the region and their relation to ocean dynamics, continental input and the choice of marine organisms used for ∆R determination. A comparison of local reservoir offsets for the Saquarema region obtained from fish otolith and mollusk shells revealed similar ΔR distributions, showing that both materials can be equally used.
Perinatal maternal high-fat (HF) diet programmes offspring obesity. Obesity is associated with overactivation of the endocannabinoid system (ECS) in adult subjects, but the role of the ECS in the developmental origins of obesity is mostly unknown. The ECS consists of endocannabinoids, cannabinoid receptors (cannabinoid type-1 receptor (CB1) and cannabinoid type-2 receptor (CB2)) and metabolising enzymes. We hypothesised that perinatal maternal HF diet would alter the ECS in a sex-dependent manner in white and brown adipose tissue of rat offspring at weaning in parallel to obesity development. Female rats received standard diet (9 % energy content from fat) or HF diet (29 % energy content from fat) before mating, during pregnancy and lactation. At weaning, male and female offspring were killed for tissue harvest. Maternal HF diet induced early obesity, white adipocyte hypertrophy and increased lipid accumulation in brown adipose tissue associated with sex-specific changes of the ECS’s components in weanling rats. In male pups, maternal HF diet decreased CB1 and CB2 protein in subcutaneous adipose tissue. In female pups, maternal HF diet increased visceral and decreased subcutaneous CB1. In brown adipose tissue, maternal HF diet increased CB1 regardless of pup sex. In addition, maternal HF diet differentially changed oestrogen receptor across the adipose depots in male and female pups. The ECS and oestrogen signalling play an important role in lipogenesis, adipogenesis and thermogenesis, and we observed early changes in their targets in adipose depots of the offspring. The present findings provide insights into the involvement of the ECS in the developmental origins of metabolic disease induced by inadequate maternal nutrition in early life.
Leishmaniasis is a neglected disease, which needs improvements in drug development, mainly due to the toxicity, parasite resistance and low compliance of patients to treatment. Therefore, the development of new chemotherapeutic compounds is an urgent need. This opinion article will briefly highlight the feasible use of calpain inhibitors as leading compounds to search for new therapeutic options to treat leishmaniasis. The milestone of this approach is to take advantage on the myriad of inhibitors developed against calpains, some of which are in advanced clinical trials. The deregulated activity of these enzymes is associated with several pathologies, such as strokes, diabetes and Parkinson's disease, to name a few. In Leishmania, calpain upregulation has been associated to drug resistance and virulence. Whereas the difficulties in developing new drugs for neglected diseases are more economical than biotechnological, repurposing approach with compounds already approved for clinical use by the regulatory agencies can be an interesting shortcut to a successful chemotherapeutic treatment for leishmaniasis.
Early Archaic human skeletal remains found in a burial context in Lapa do
Santo in east-central Brazil provide a rare glimpse into the lives of
hunter-gatherer communities in South America, including their rituals for
dealing with the dead. These included the reduction of the body by means of
mutilation, defleshing, tooth removal, exposure to fire and possibly
cannibalism, followed by the secondary burial of the remains according to
strict rules. In a later period, pits were filled with disarticulated bones
of a single individual without signs of body manipulation, demonstrating
that the region was inhabited by dynamic groups in constant transformation
over a period of centuries.
This work describes the effects of different atmospheres used during the thermal treatment of hematite films synthesized on transparent conductive substrates of fluorine-doped tin oxide by a newly reported wet chemical route assisted by microwave. The as-synthesized films were subjected to additional thermal treatment at 750 °C for 30 min in different gas flux (air, O2, and N2) to obtain a desirable phase and surface activation. A series of techniques were used to elucidate effects of each atmosphere used during the thermal treatment. The morphology of the films, as analyzed by top-view and cross-sectional scanning electron microscopy images, showed no significant changes and was composed of rods homogeneously distributed over the substrate, which covered the immersed area with a thickness between 98 and 100 nm. The photoelectrochemical response of the N2-hematite films was found to be 80 and 50% more efficient at 1.23 VRHE (reversible hydrogen electrode) than those of films produced in air and an O2 atmosphere. The photocurrent enhancement achieved by treatment in an oxygen-deficient atmosphere was attributed to the improvement of hematite catalytic activity, which produced a hematite–electrolyte interface favorable for water oxidation. Since an increase in the donor density by one order of magnitude was found for the N2-hematite films, a reduction of charge transfer resistance was expected in these films. However, the Nyquist plot analysis showed that the O2-hematite film had a lower charge transfer resistance. As a result, it is impossible to relate the photocurrent enhancement observed in N2-hematite film to electronic changes or vacancy formation, as previously reported in the literature. Indeed, by performing photoelectrochemical measurements in the presence of hole scavengers, it became clear that the major improvement caused by the oxygen-deficient atmosphere was in the catalytic activity efficiency of the hematite films for water oxidation. It was found that the oxygen-deficient atmosphere could improve the overall photoelectrochemical performance of the hematite by acting as a hole scavengers. This finding contrasts with a previous report, in which the use of an oxygen-deficient atmosphere during the phase transformation from akaganeite to hematite was found to enhance the photocurrent density by inducing an increased donor density caused by the formation of vacancies [Y. Ling et al., Angew. Chem., Int. Ed.51, 4074 (2012)].
Skin samples were used to compare microscopy methods used to quantify collagen with potential applicability to resolve time-dependent collagen deposition during skin wound healing in rats. Skin wounds by secondary intention were made in rats and tissue fragments were collected every 7 days for 21 days. Collagen content determined by biochemical analysis was compared with collagen measured by point counting (PC) on histological skin sections stained by Gomori’s trichrome method (Trichrome/PC), Sirius red under polarized light (PL) microscopy (Sirius red/PL-PC), and computational color segmentation (CS) applied to sections stained with Sirius red (Sirius red/PL-CS). All microscopy methods investigated resolved the time-dependent dynamics of collagen deposition in scar tissue during skin wound healing in rats. Collagen content measured by Sirius red/PL-PC and Sirius red/PL-CS was significantly lower when compared with Trichrome/PC. The Trichrome/PC method provided overestimated values of collagen compared with biochemical analysis. In the early stages of wound healing, which shows high production of noncollagenous molecules, Sirius red/PL-CS and Sirius red/PL-PC methods were more suitable for quantification of collagen fibers. Trichrome staining did not allow clear separation between collagenous and noncollagenous elements in skin samples, introducing a marked bias in collagen quantification.
Bacteriocins are natural compounds used as food biopreservatives instead of chemical preservatives. Bifidobacterium animalis subsp. lactis (Bifid. lactis) was shown to produce a bacteriocin-like inhibitory substance (BLIS) able to inhibit the growth of Listeria monocytogenes selected as an indicator microorganism. To enhance this production by the strain Bifid. lactis BL 04, skim milk (SM) was used as a fermentation medium either in the presence or in the absence of yeast extract, Tween 80 or inulin as stimulating additives, and the results in terms of bacterial growth and BLIS production were compared with those obtained in a traditional high cost complex medium such as Man, Rogosa and Sharpe (MRS). To this purpose, all the cultivations were carried out in flasks at 200 rpm under anaerobic conditions ensured by a nitrogen flowrate of 1·0 L/min for 48 h, and BLIS production was quantified by means of a modified agar diffusion assay at low values of both temperature and concentration of List. monocytogenes. Although all these ingredients were shown to exert positive influence on BLIS production in both media, yeast extract and SM were by far the best ingredient and the best medium, respectively, allowing for a BLIS production at the late exponential phase of 2000 AU/ml.
Intestinal mucositis is an important toxic side effect of 5-fluorouracil (5-FU) treatment. Saccharomyces boulardii is known to protect from intestinal injury via an effect on the gastrointestinal microbiota. The objective of the present study was to evaluate the effect of S. boulardii on intestinal mucositis induced by 5-FU in a murine model. Mice were divided into saline, saline (control)+5-FU or 5-FU+S. boulardii (16 × 109 colony-forming units/kg) treatment groups, and the jejunum and ileum were removed after killing of mice for the evaluation of histopathology, myeloperoxidase (MPO) activity, and non-protein sulfhydryl group (mainly reduced glutathione; GSH), nitrite and cytokine concentrations. To determine gastric emptying, phenol red was administered orally, mice were killed 20 min after administration, and the absorbance of samples collected from the mice was measured by spectrophotometry. Intestinal permeability was measured by the urinary excretion rate of lactulose and mannitol following oral administration. S. boulardii significantly reversed the histopathological changes in intestinal mucositis induced by 5-FU and reduced the inflammatory parameters: neutrophil infiltration (control 1·73 (sem 0·37) ultrastructural MPO (UMPO)/mg, 5-FU 7·37 (sem 1·77) UMPO/mg and 5-FU+S. boulardii 4·15 (sem 0·73) UMPO/mg); nitrite concentration (control 37·00 (sem 2·39) μm, 5-FU 59·04 (sem 11·41) μm and 5-FU+S. boulardii 37·90 (sem 5·78) μm); GSH concentration (control 477·60 (sem 25·25) μg/mg, 5-FU 270·90 (sem 38·50) μg/mg and 5-FU+S. boulardii 514·00 (sem 38·64) μg/mg). Treatment with S. Boulardii significantly reduced the concentrations of TNF-α and IL-1β by 48·92 and 32·21 % in the jejunum and 38·92 and 61·79 % in the ileum. In addition, S. boulardii decreased the concentrations of chemokine (C–X–C motif) ligand 1 by 5-fold in the jejunum and 3-fold in the ileum. Interestingly, S. boulardii reduced the delay in gastric emptying (control 25·21 (sem 2·55) %, 5-FU 54·91 (sem 3·43) % and 5-FU+S. boulardii 31·38 (sem 2·80) %) and induced the recovery of intestinal permeability (lactulose:mannitol ratio: control 0·52 (sem 0·03), 5-FU 1·38 (sem 0·24) and 5-FU+S. boulardii 0·62 (sem 0·03)). In conclusion, S. boulardii reduces the inflammation and dysfunction of the gastrointestinal tract in intestinal mucositis induced by 5-FU.
The aim of this study was to evaluate the relationship between drug use and four kinds of stress symptoms in 954 Brazilian students from the 6th to the 11th grades, in 4 public and 5 private schools in the city of Sao Paulo. Based on their answers to the Drug Use Screening Inventory (DUSI-R) and to the Stress Scale for Adolescents (SSA), we compared regular drug users with non/occasional drug users regarding the frequency of four kinds of stress symptoms (psychological, cognitive, physiological, interpersonal), and the period in which it happened. When compared to non/occasional drug users, regular drug users presented higher levels of psychological, cognitive and physiological symptoms of stress and these symtoms were in the most severe spectrum of severity (near to exhaustion and exhaustion). The association between drug use and stress was even stronger in the youngest age group (11 to 13 years old). Most of the regular drug users were 16 years old and over, from upper-middle class families, had poor family relationships and more academic problems. These results confirm the association between drug use and stress in adolescents and highlight the need for early screening and intervention in both drug use and stressful situations.
During the Pleistocene a fauna composed of large (biomass > 44 kg) and giant mammals (biomass > 1000 kg) that are usually associated with open environments lived in the Brazilian Intertropical Region. We present here new information concerning the paleoecology and chronology of some species of this megafauna. Carbon isotope analyses were performed for a better understanding of the paleoecology of the species Eremotherium laurillardi (Lund, 1842), Notiomastodon platensis (Ameghino, 1888) and Toxodon platensis (Owen, 1849). The δ13C data allow attributing a generalist diet to these species, which varied according to the kind of habitat in which they lived. In more open habitats all species were grazers; in mixed habitats E. laurillardi and T. platensis were mixed feeders, and N. platensis was grazer; and in more closed habitats all species were mixed feeders.
A large and increasing share of international humanitarian and development aid is raised from nongovernmental sources, allocated by transnational NGOs. We know little about this private foreign aid, not even how it is distributed across recipient countries, much less what explains the allocation. This article presents an original data set, based on detailed financial records from most of the major U.S.-based humanitarian and development NGOs, which allows us for the first time to map and analyze the allocation of U.S. private aid. We find no support for the common claim that aid NGOs systematically prioritize their organizational self-interest when they allocate private aid, and we find only limited support for the hypothesis that expected aid effectiveness drives aid allocation. By contrast, we find strong support for the argument that the deeply rooted humanitarian discourse within and among aid NGOs drives their aid allocation, consistent with a view of aid NGOs as principled actors and constructivist theories of international relations. Recipients' humanitarian need is substantively and statistically the most significant determinant of U.S. private aid allocation (beyond a regional effect in favor of Latin American countries). Materialist concerns do not crowd out ethical norms among these NGOs.