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Chagas disease (CD) is a neglected parasitic condition endemic in the Americas caused by Trypanosoma cruzi. Patients present an acute phase that may or not be symptomatic, followed by lifelong chronic stage, mostly indeterminate, or with cardiac and/or digestive progressive lesions. Benznidazole (BZ) and nifurtimox are the only drugs approved for treatment but not effective in the late chronic phase and many strains of the parasite are naturally resistant. New alternative therapy is required to address this serious public health issue. Repositioning and combination represent faster, and cheaper trial strategies encouraged for neglected diseases. The effect of imatinib (IMB), a tyrosine kinase inhibitor designed for use in neoplasias, was assessed in vitro on T. cruzi and mammalian host cells. In comparison with BZ, IMB was moderately active against different strains and forms of the parasite. The combination IMB + BZ in fixed-ratio proportions was additive. Novel 14 derivatives of IMB were screened and a 3,2-difluoro-2-phenylacetamide (3e) was as potent as BZ on T. cruzi but had low selectivity index. The results demonstrate the importance of phenotypic assays, encourage the improvement of IMB derivatives to reach selectivity and testify to the use of repurposing and combination in drug screening for CD.
The average patterns of the velocity and scalar fields near turbulent/non-turbulent interfaces (TNTI), obtained from direct numerical simulations (DNS) of planar turbulent jets and shear free turbulence, are assessed in the strain eigenframe. These flow patterns help to clarify many aspects of the flow dynamics, including a passive scalar, near a TNTI layer, that are otherwise not easily and clearly assessed. The averaged flow field near the TNTI layer exhibits a saddle-node flow topology associated with a vortex in one half of the interface, while the other half of the interface consists of a shear layer. This observed flow pattern is thus very different from the shear-layer structure consisting of two aligned vortical motions bounded by two large-scale regions of uniform flow, that typically characterizes the average strain field in the fully developed turbulent regions. Moreover, strain dominates over vorticity near the TNTI layer, in contrast to internal turbulence. Consequently, the most compressive principal straining direction is perpendicular to the TNTI layer, and the characteristic 45-degree angle displayed in internal shear layers is not observed at the TNTI layer. The particular flow pattern observed near the TNTI layer has important consequences for the dynamics of a passive scalar field, and explains why regions of particularly high scalar gradient (magnitude) are typically found at TNTIs separating fluid with different levels of scalar concentration. Finally, it is demonstrated that, within the fully developed internal turbulent region, the scalar gradient exhibits an angle with the most compressive straining direction with a peak probability at around 20
. The scalar gradient and the most compressive strain are not preferentially aligned, as has been considered for many years. The misconception originated from an ambiguous definition of the positive directions of the strain eigenvectors.
Graded exercises tests are performed in adult populations; nonetheless, the use of this type of assessment is greatly understudied in overweight and obese adolescents.
To investigate heart rate autonomic responses to submaximal aerobic exercise in obese and overweight adolescents.
We recruited 40 adolescents divided into two groups: (1) overweight group comprising 10 boys and 10 girls between Z-score +1 and +2 and (2) obese group comprising 10 boys and 10 girls above Z-score >+2. Heart rate variability was analysed before (T1) and after exercise (T2–T4) on treadmill at a slope of 0%, with 70% of the maximal estimated heart rate (220 – age) for 20 minutes.
Heart rate in the overweight group was: 93.2±10.52 bpm versus 120.8±13.49 bpm versus 94.6±11.65 bpm versus 93.0±9.23 bpm, and in the obese group was: 92.0±15.41 bpm versus 117.6±16.31 bpm versus 92.1±12.9 bpm versus 91.8±14.33 bpm. High frequency in the overweight group was: 640±633.1 ms2 versus 84±174.66 ms2 versus 603.5±655.31 ms2 versus 762.6±807.21 ms2, and in the obese group was: 628.4±779.81 ms2 versus 65.4±119.34 ms2 versus 506.2±482.70 ms2 versus 677.9±939.05 ms2; and root mean square of successive differences in the overweight group was: 37.9±18.81 ms versus 10.9±8.41 ms versus 32.8±24.07 ms versus 36.7±21.86 ms, and in the obese group was: 38.7±23.17 ms versus 11.5±8.62 ms versus 32.3±16.74 ms versus 37.3±24.21 ms. These values significantly changed during exercise compared with resting values in overweight and obese groups. Moreover, we also reported no significant difference of resting parasympathetic control of heart rate between obese and overweight adolescents.
There was no significant difference of autonomic responses elicited by submaximal aerobic exercise between overweight and obese adolescents.
We evaluated the effects of cattle manure and inoculation with arbuscular mycorrhizal fungi (AMF) in maize plants growing in a semiarid area of Brazilian north-east in 2012 and 2013. Three isolates of AMF (Acaulospora longula URM-FMA 07 and URM-FMA 03, Claroideoglomus etunicatum UNIVASF 06A) were used, with or without the application of cattle manure, during two growing cycles. In the first year, significant effects of inoculation were detected for straw yield only when the manure was applied. In the second year, there was an interaction between fertilisation and inoculation for plant height and grain yield, with the highest values in the fertilised treatments. Inoculation with A. longula demonstrated that mycorrhizal inoculation in field-grown plants could be an alternative management for improving plant growth and grain yield, reducing the use of cattle manure. The AMF sporulation and mycorrhizal colonisation were improved after inoculation, and A. longula URM-FMA 07 increased sporulation by more than 15 times while inoculation with C. etunicatum increased sporulation by more than 3 times. The mycorrhizal inoculation is a management practice that can be useful for recovering or maintaining AMF infective propagules in soil, showing potential to be used in large-scale field conditions in Brazilian semiarid. Although mycorrhisation presents high agricultural relevance due to benefits promoted to the soil and plants, the knowledge about the factors influencing the interactions among microorganisms, soil and plants need to be broadened aiming to achieve successful crop management in semiarid regions.
The increase of sheep meat competitiveness in international markets can be attributed to the rise of the quantity and the improvement of the quality of the edible portion of sheep carcasses. Usually, carcass yield is established after the slaughter of the animals. Yet, when carcass yield is determined in vivo, it can be both a costly and subjective method. This study proposes models for predicting the physical characteristics of lamb carcass using bioimpedance analysis (BIA) in live animals. Thirty-one Texel × Ile de France crossbreed ram lambs were slaughtered at 20, 26, 32 or 38 kg of BW. Before the slaughter, values of resistance (Rs) and reactance (Xc) were collected using a single-frequency BIA equipment (Model RJL Quantum II Bioelectrical Body Composition Analyzer). Then, BIA main variables such as body bioelectrical volume (V), phase angle (PA), resistive density (RsD) and reactive density (XcD) were calculated. After slaughter, cold carcass weight (CCW), cold carcass yield (CCY), subcutaneous fat thickness (SFT), soft tissue weight (STW) and soft tissue yield (STY) were also measured. Multiple regression analyses were carried out using the physical characteristics as dependent variables and the bioimpedance values as independent variables. Predictive performance of the models was assessed using leave-one-out cross-validation. The prediction model of CCW was obtained using the V, PA and RsD (R2 = 0.97), STW through the V, RsD and XcD (R2 = 0.97), CCY by Rs, Z and XcD (R2 = 0.69), STY by V and XcD (R2 = 0.67), and SFT only for XcD (R2 = 0.84). The results indicated that BIA has the potential to predict carcass characteristics of lambs at different body masses.
Salivary molecules, as glycine-rich proteins (GRPs), are essential to tick attachment and feeding on the host and are suggested to be involved in the host's immune system evasion, therefore representing natural candidates in the search for protective vaccine antigens. This work shows the molecular characterization of a GRP from Rhipicephalus microplus (RmGRP). The cDNA and putative amino acid sequences were analysed, as well as the transcription level in tick tissues/developmental stages, showing the highest levels of gene expression in 1-day-old larvae and salivary glands of fully engorged females. RmGRP gene silencing resulted in a lower hatching rate of larvae from treated females. In addition, recombinant RmGRP (rRmGRP) was recognized by sera from naturally and experimentally infested bovines, displaying considerable differences among the individuals tested. rRmGRP was recognized by anti-saliva and anti-salivary glands sera, while anti-rRmGRP serum recognized RmGRP in saliva and salivary glands, indicating its secretion into the host. The data collected indicate that RmGRP may present roles other than in the tick–host relationship, especially in embryo development. In addition, the high expression in adult females, antigenicity and presence of shared characteristics with other tick protective GRPs turns RmGRP a potential candidate to compose an anti-tick vaccine cocktail.
The scaling of turbulent motions is investigated by considering the flow in the eigenframe of the local strain-rate tensor. The flow patterns in this frame of reference are evaluated using existing direct numerical simulations of homogeneous isotropic turbulence over a Reynolds number range from
up to 1131, and also with reference to data for inhomogeneous, anisotropic wall turbulence. The average flow in the eigenframe reveals a shear layer structure containing tube-like vortices and a dissipation sheet, whose dimensions scale with the Kolmogorov length scale,
. The vorticity stretching motions scale with the Taylor length scale,
, while the flow outside the shear layer scales with the integral length scale,
. Furthermore, the spatial organization of the vortices and the dissipation sheet defines a characteristic small-scale structure. The overall size of this characteristic small-scale structure is
in all directions based on the coherence length of the vorticity. This is considerably larger than the typical size of individual vortices, and reflects the importance of spatial organization at the small scales. Comparing the overall size of the characteristic small-scale structure with the largest flow scales and the vorticity stretching motions on the scale of
shows that transitions in flow structure occur where
and 250. Below these respective transitional Reynolds numbers, the small-scale motions and the vorticity stretching motions are progressively less well developed. Scale interactions are examined by decomposing the average shear layer into a local flow, which is induced by the shear layer vorticity, and a non-local flow, which represents the environment of the characteristic small-scale structure. The non-local strain is
in width and height, which is consistent with observations in high Reynolds number flow of a
wide instantaneous shear layer with many
-scale vortical structures inside (Ishihara et al., Flow Turbul. Combust., vol. 91, 2013, pp. 895–929). In the average shear layer, vorticity aligns with the intermediate principal strain at small scales, while it aligns with the most stretching principal strain at larger scales, consistent with instantaneous turbulence. The length scale at which the alignment changes depends on the Reynolds number. When conditioning the flow in the eigenframe on extreme dissipation, the velocity is strongly affected over large distances. Moreover, the associated peak velocity remains Reynolds number dependent when normalized by the Kolmogorov velocity scale. It signifies that extreme dissipation is not simply a small-scale property, but is associated with large scales at the same time.
Cepheids are excellent stellar tracers: they are bright enough to be observed even at large distances; their distances can be accurately determined via period-luminosity relations; their spectra contain numerous lines that enable us to derive abundances for many α, iron-peak or neutron-capture elements. Classical Cepheids are yellow supergiants that trace the young populations (⩽ 300 Myr); Type II Cepheids are post Horizontal Branch, low-mass, Population II stars (⩾ 10 Gyr). Both can be used for many purposes in Milky Way archaeology.
Plants’ ability to rebuild their tiller population is affected by weather changes and management strategies. The hypothesis of the present study was that frequency and severity of defoliation alter Mulato grass (Brachiaria ruziziensis × Brachiaria brizantha cv. Marandu) sward development, and the proportion of aerial and basal tillers, interfering with sward stability. The objective was to evaluate aerial, basal and total tiller population density and changes in tillering dynamics. Treatments corresponded to strategies of rotational grazing characterized by combinations between two pre-grazing (95% and maximum canopy light interception during regrowth; LI95% and LIMax) and two post-grazing conditions (15 and 20 cm stubble height). The experimental period comprised four seasons of the year: summer 2008 (February–March 2008); autumn–early spring (April to mid-November 2008); late spring (mid-November–December 2008); and summer 2009 (January–March 2009). Density of aerial tillers decreased from summer 2008 to late spring. Tiller death decreased from summer 2008 to autumn–early spring. Aerial and total tiller death increased from late spring to summer 2009, mainly for the LI95% treatment. No differences were observed in the tiller population stability index of aerial tillers for LI treatments or post-grazing heights. The balance between tiller appearance and death for basal tillers remained relatively stable from summer 2008 to late spring. For aerial tillers the balance decreased to negative values from summer 2008 to autumn–early spring for both LI treatments. For total tiller population, the balance decreased to negative values from summer 2008 to autumn–early spring. Results indicated a strong seasonal effect on Mulato grass tillering and growth. Tillering dynamics were affected primarily by grazing frequency, which changed the relative importance of basal and aerial tillers. The results suggested that basal tillering was the predominant perennation pathway.
We analyse the behavior of the projected rotational velocity vsin i for a sample of 20 lithium-rich evolved stars. Most of these stars show normal rotational velocity with respect to the typical lithium-normal evolved stars of the same spectral type. Stars presenting enhanced rotation show also high activity level. No sign of binarity was found for these lithium-rich evolved stars.
The mechanical behavior of superconductor lamellar-like BaFe2As2 single crystals was investigated at nanoscale by instrumented indentation. The unique responses of the ab- and a(b)c-crystallographic planes were discussed based on their influence in hardness (H) and elastic modulus (E). The results allowed two main conclusions. (i) The choice of testing parameters strongly affected the scaling of mechanical properties on the lamellar surfaces. Lamellar cracking was the leading mechanism of deformation, featuring a brittle-like behavior and affecting considerably H and E. However, the plastic deformation history allowed different elastic–plastic responses on the ab-plane owing to the compaction of the material. Threshold loads for cracking depended on both loading rate and penetration velocity, pointing out to time-dependent plastic deformation mechanisms. (ii) Proper estimates were achieved for H in multiple loading tests [3.4 GPa for ab- and ∼1 GPa for a(b)c-planes], and for E under loads less than 3 mN (∼55 GPa for both planes).
A micro heteregenous reprocessed fuel spiked with thorium in a PWR fuel element considering (TRU-Th) cycle was simulated using three different configurations and different fissile materials that varied from 6.0% to 7.0%. The reprocessed fuels were obtained using the ORIGEN 2.1 code from a burned PWR standard fuel (33,000 MWd/tHM burned), with 3.1% of initial enrichment, which was remained in the cooling pool for five years and then reprocessed using UREX+ technique. The keff and plutonium generation during the burnup were evaluated and compared with the standard fuel. This study was performed using the SCALE 6.0.
The enzymatic activities of NTPDase and 5′nucleotidase are important to regulate the concentration of adenine nucleotides, known molecules involved in many physiological functions. Therefore, the objective of this study was to evaluate the activity of NTPDase and 5′nucleotidase in serum and liver tissue of rats infected by Fasciola hepatica. Rats were divided into two groups: uninfected control and infected. NTPDase activity for adenosine triphosphate (ATP) and ADP substrates in the liver was higher compared with the control group at 15 days post-infection (PI), while seric activity was lower. In addition, seric and hepatic samples did not show changes for 5′nucleotidase activity at this time. On the other hand, either NTPDase or 5′nucleotidase activities in liver homogenate and serum were higher at 87 days PI. Early in the infection, low NTPDase activity maintains an increase of ATP in the bloodstream in order to activate host immune response, while in hepatic tissue it decreases extracellular ATP to maintain a low inflammatory response in the tissue. As stated, higher NTPDase and 5′nucleotidase activities 87 days after infection in serum and tissue, probably results on an increased concentration of adenosine molecule which stimulates a Th2 immune response. Thus, it is possible to conclude that F. hepatica infections lead to different levels of nucleotide degradation when considering the two stages of infection studied, which influences the inflammatory and pathological processes developed by the purinergic system.
The objective of this study was to investigate relationships between ovulation rate (OR) and embryonic and placental development in sows. Topigs Norsvin® sows (n=91, parity 2 to 17) from three different genetic backgrounds were slaughtered at 35 days of pregnancy and the reproductive tract was collected. The corpora lutea (CL) were counted and the number of vital and non-vital embryos, embryonic spacing (distance between two embryos), implantation length, placental length, placental weight and embryonic weight were assessed. The difference between number of CL and total number of embryos was considered as early embryonic mortality. The number of non-vital embryos was considered as late mortality. Relationships between OR and all other variables were investigated using two models: the first considered parity as class effect (n=91) and the second used a subset of sows with parities 4 to 10 (n=47) to analyse the genetic background as class effect. OR was significantly affected by parity (P<0.0001), but was not affected by the genetic background of the sows. Parity and genetic background did not affect embryonic and placental characteristics at 35 days of pregnancy. OR (varying from 17 to 38 CL) was positively related with early embryonic mortality (β=0.49±0.1 n/ovulations, P<0.0001), with late embryonic mortality or number of non-vital embryos (β=0.24±0.1 n/ovulations, P=0.001) and with the number of vital embryos (β=0.26±0.1 n/ovulations, P=0.01). However, dividing OR in four classes, showed that the number of vital embryos was lowest in OR class 1 (17 to 21 CL), but not different for the other OR classes, suggesting a plateau for number of vital embryos for OR above 22. There was a negative linear relationship between OR and vital embryonic spacing (β=−0.45±0.1 cm/ovulation, P=0.001), implantation length (β=−0.35±0.1 cm/ovulation, P=0.003), placental length (β=−0.38±0.2 cm/ovulation, P=0.05) and empty space around embryonic-placental unit (β=−0.4±0.2 cm/ovulation, P=0.02), indicating uterine crowding. Further analyses showed that effects of OR on embryonic and uterine parameters were related with the increase in late mortality and not early embryonic mortality. Therefore, we conclude that a high OR results in an moderate increase in the number of vital embryos at day 35 of pregnancy, but compromises development in the surviving embryonic/placental units, suggesting that the future growth and survival of the embryos might be further compromised.
Human toxocarosis is a chronic tissue parasitosis most often caused by Toxocara canis. The seroprevalence can reach up to 50%, especially among children and adolescents. The anthelmintics used in the treatment have moderate efficacy. The aim of this study was to evaluate the in vitro and in vivo anthelmintic activity of quinones and their derivatives against T. canis larvae and the cytotoxicity of the larvicidal compounds. The compounds were evaluated at 1 mg mL−1 concentration in microculture plates containing third stage larvae in an Roswell Park Memorial Institute (RPMI) 1640 environment, incubated at 37 °C in 5% CO2 tension for 48 h. Five naphthoxiranes were selected for the cytotoxicity analysis. The cell viability evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays using murine peritoneal macrophages isolated from C57BL/6 mice revealed that the naphthoxiranes (1 and 3) were less cytotoxic at a concentration of 0·05 mg mL−1. The efficacy of naphthoxiranes (1 and 3) was examined in murine toxocarosis also. The anthelmintic activity was examined by evaluating the number of larvae in the brain, carcass, liver, lungs, heart, kidneys and eyes. Compound (3) demonstrated anthelmintic activity similar to that of albendazole by decreasing the number of larvae in the organs of mice and thus could form the basis of the development of a new anthelmintic drug.
Obesity and osteoporosis may have their origins in early postnatal life. This study was designed to evaluate whether flaxseed flour use during lactation period bears effect on body adiposity and skeletal structure of male rat pups at weaning. At birth, male Wistar rats were randomly assigned to control and experimental (FF) groups, whose dams were treated with control or flaxseed flour diet, respectively, during lactation. At 21 days of age, pups were weaned to assess body mass, length and composition by dual-energy X-ray absorptiometry. The animals were then sacrificed to carry out analysis of serum profile, intra-abdominal adipocyte morphology and femur characteristics. Differences were considered significant when P<0.05. The FF group displayed the following characteristics (P<0.05): higher body mass, length, bone mineral content, bone area and concentrations of osteoprotegerin, osteocalcin and high-density lipoprotein cholesterol; higher levels of stearic, α-linolenic, eicosapentaenoic and docosapentaenoic acids and lower levels of arachidonic acid and cholesterol; smaller adipocyte area; and higher mass, epiphysis distance, diaphysis width, maximal load, break load, resilience and stiffness of femur. Flaxseed flour intake during lactation period promoted adipocyte hypertrophy down-regulation and contributed to pup bone quality at weaning.
The aim of this study was analyzed if the flour or flaxseed oil treatment contributes to body composition in male rats subjected to early weaning. Pups were weaned for separation from mother at 14 (early weaning, EW) and 21 days (control, C). At 21 days, part of the pups was evaluated (C21 v. EW21). After 21 days, control (C60) was fed with control diet. EW was divided in control (EWC60); flaxseed flour (EWFF60); flaxseed oil (EWFO60) diets until 60 days. Body mass, length and body composition by dual-energy X-ray absorptiometry were determined. EW21 (v. C21) and EWC60 (v. C60 and EWFF60) showed lower (P<0.05) mass, length and body composition. EWFO60 (v. C60 and EWFF60) showed lower (P<0.05) body mass and length, body and trunk lean mass, bone mineral density and content and bone area. Flaxseed flour, in comparison with flaxseed oil, contributes to recovery of body composition after early weaning.
The precocious interruption of lactation is a prime factor for developmental plasticity. Here we analyzed whether flour or flaxseed oil treatment contributes to body and brain mass in male rats subjected to early weaning. Pups were weaned for separation from their mother at 14 (early weaning, EW) and 21 days (control, C). At 21 days, some of the pups were evaluated (C21 v. EW21). After 21 days, control pups (C60) were fed a control diet. EW pups were divided into those fed a control diet (EWC60), those given flaxseed flour (EWFF60), and those given flaxseed oil (EWFO60) until 60 days. EW21 showed lower body and absolute brain mass and higher relative brain mass. At 60 days, EWC60 and EWFO60 had lower body mass. With regard to relative brain mass, EWC60 was heavier; EWFO60 had lower values compared with EWC60 and higher values compared with C60 and EWFF60. These results indicated that flaxseed flour, in comparison with flaxseed oil, contributes to brain development after EW.