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The multipolar representation of the magnetic field has, for the lowest-order term, a magnetic dipole that dominates the far field. Thus the far-field representation of the magnetic field of the Earth, Sun and other celestial bodies is a dipole. Since these bodies consist of or are surrounded by plasma, which can support Alfvén waves, their propagation along dipole magnetic field lines is considered using a new coordinate system: dipolar coordinates. The present paper introduces multipolar coordinates, which are an example of conformal coordinates; conformal coordinates are orthogonal with equal scale factors, and can be extended from the plane to space, for instance as cylindrical or spherical dipolar coordinates. The application considered is to Alfvén waves propagating along a circle, that is a magnetic field line of a dipole, with transverse velocity and magnetic field perturbations; the various forms of the wave equation are linear second-order differential equations, with variable coefficients, specified by a background magnetic field, which is force free. The absence of a background magnetic force leads to a mean state of hydrostatic equilibrium, specified by the balance of gravity against the pressure gradient, for a perfect gas or incompressible liquid. The wave equation is simplified to a Gaussian hypergeometric type in the case of zero frequency, otherwise, for non-zero frequency, an extended Gaussian hypergeometric equation is obtained. The solution of the latter specifies the magnetic field perturbation spectrum, and also, via a polarisation relation, the velocity perturbation spectrum; both are plotted, over half a circle, for three values of the dimensionless frequency.
Recruitment of the limpet Patella ulyssiponensis was investigated in relation to the presence of living crustose coralline algae (CCA) in rocky-shore habitats. Juvenile limpets (≤10 mm maximum shell length) were counted in CCA-present and CCA-absent habitats, on three shores in SW Portugal during summer 2007 and winter 2009. Furthermore, the settling response of laboratory-reared larvae of P. ulyssiponensis to CCA-covered substratum, and bare-rock, was examined. Across the intertidal zone, we found a clear association between the distribution and abundance of juveniles and the presence of CCA. Although the presence of CCA was not an absolute requisite for juvenile occurrence, null juvenile densities were mostly recorded in CCA-absent areas. The highest juvenile densities (maximum of 64 individuals in 15 × 15 cm) were consistently found in CCA-dominated habitats, namely steep wave-exposed areas at low-shore and rock-pools. The hypothesis of CCA-enhanced settlement was not supported, as settlement intensities of laboratory-reared larvae were similar between chips of rock encrusted by CCA and chips of bare-rock. From the overall number of settlers onto CCA-encrusted rock chips, 51% were found in tiny pits lacking CCA. This was the first study of the settlement patterns of larvae of the genus Patella using naturally occurring rocky substrata. These results are preliminary and should be confirmed with choice-experiments and improved monitoring of the position of settlers. We suggest that CCA plays a role in the recruitment of P. ulyssiponensis, potentially promoting survivorship of early benthic stages, but possibly not enhancing settlement.
Consanguineous marriages potentially play an important role in the transmission of β-thalassaemia in many communities. This study aimed to determine the rate and socio-demographic associations of consanguineous marriages and to assess the influence on the prevalence of β-thalassaemia in Sri Lanka. Three marriage registrars from each district of Sri Lanka were randomly selected to prospectively collect data on all couples who registered their marriage during a 6-month period starting 1st July 2009. Separately, the parents of patients with β-thalassaemia were interviewed to identify consanguinity. A total of 5255 marriages were recorded from 22 districts. The average age at marriage was 27.3 (±6.1) years for males and 24.1 (±5.7) years for females. A majority (71%) of marriages were ‘love’ marriages, except in the Moor community where 84% were ‘arranged’ marriages. Overall, the national consanguinity rate was 7.4%. It was significantly higher among ethnic Tamils (22.4%) compared with Sinhalese (3.8%) and Moors (3.2%) (p < 0.001). Consanguinity rates were also higher in ‘arranged’ as opposed to ‘love’ marriages (11.7% vs 5.6%, p < 0.001). In patients with β-thalassaemia, the overall consanguinity rate was 14.5%; it was highest among Tamils (44%) and lowest among Sinhalese (12%). Parental consanguinity among patients with β-thalassaemia was double the national average. Although consanguinity is not the major factor in the transmission of the disease in the country, emphasis should be given to this significant practice when conducting β-thalassaemia prevention and awareness campaigns, especially in high-prevalence communities.
The BW has been largely used as a selection criterion in genetic selection programmes; however, increases in BW can affect animal metabolism and metabolites. The knowledge of how genetic potential for growth affects the metabolites can give a footprint of growth metabolism. This research aimed to evaluate the effect of genetic potential for post-weaning growth (GG) on performance, carcass traits and serum metabolome of non-castrated Nellore males during the finishing phase. Forty-eight Nellore non-castrated males, with divergent potential for post-weaning growth, were selected and divided into two groups: high potential for post-weaning growth (HG; n = 24) and low potential for post-weaning growth (LG; n = 24). Animals were kept and fed for 90 days where performance and ultrasound carcass traits were evaluated. Blood samples were collected at the beginning and end of feeding period to analyse serum metabolites concentration. The hot carcass weight and dressing percentage were recorded at slaughter. The feedlot performance and carcass traits were not affected by genetic potential. The HG animals had a lower glucose (P = 0.039), glutamate (P = 0.038), glutamine (P = 0.004), greater betaine (P = 0.039) and pyruvate (P = 0.039) compared to the LG group at the beginning of feedlot. In addition, higher creatine phosphate concentrations were observed at the beginning of feeding period, compared to final, for both groups (P = 0.039). In conclusion, the genetic potential for post-weaning growth does not affect performance and carcass traits during the finishing period. Differences in metabolite concentrations can be better found at the beginning of feedlot, providing a footprint of growth metabolism, but similar metabolite concentration at the end of finishing period.
Dietary protein adjustments can reduce environmental impact and economic losses in production systems. However, we lack information regarding nitrogen (N) metabolism and protein requirements for maintenance of crossbred animals such as Red Norte breed, precluding a precise dietary management. The objective was to evaluate the effect of increasing dietary CP levels (9%, 11%, 13%, 15% and 17%) on intake, digestibility and N balance, as well as to estimate the metabolizable protein requirements for maintenance (MPm) of growing Red Norte bulls. Thirty five animals averaging 280 ± 4.0 kg BW were fed during 45 days in a 60 : 40 forage : concentrate ratio diet in which the last 5 days were used for the digestibility trial. Intakes of CP and non-fibrous carbohydrates (NFCs) and feed efficiency linearly increased (P < 0.05) as CP levels increased, while DM, NDF, nitrogen efficiency use and ether extract were not influenced by CP levels (P > 0.05). Digestibilities of DM, organic matter, ether extract, NFC and CP as well as metabolizable energy intake linearly increased (P < 0.05), and true digestibility of CP was not affected (P > 0.05) by treatments. Urinary N and retained N linearly increased (P < 0.05) with the increase in dietary N. The MPm were estimated as 4.46 g/BW0.75 and the efficiency of use of MPm was 0.673. In conclusion, obtained MPm requirements of growing Red Norte bulls are greater than the values reported in literature for Zebu cattle and dietary CP levels of 15% and 17% exhibited great responses for growing Red Norte cattle. However, a cost-benefit evaluation should be done before its use.
Partial amount of austenite can be dynamically transformed into ferrite above the Ae3 temperature when it is being deformed. This happens by a displacive mechanism. On removal of the load, it retransforms back into the stable austenite by diffusional processes. Plate rolling simulation under continuous cooling conditions was carried out on a high Nb X70 steel. Pass strains of 0.2 together with interpass times of 10, 20 and 30 s were employed. The initial and final temperatures for the finishing simulation were 920 and 830 °C, respectively. The mean flow stresses (MFS`s) behaviour indicates that dynamic transformation (DT) and recrystallization (DRX) were taking place during straining. It is shown that ferrite is formed during the roughing passes and increases its volume fraction throughout the finishing rolling steps. The ferrite formation is favoured by strain accumulation, shorter time between passes and also when the temperature reaches the Ae3 line. The results obtained here can be used to design improved models for transformation on accelerated cooling.
The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
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.
With still limited information on vitamin requirements and considering that many commercial practices adopt dietary vitamin levels above the values suggested by nutritional tables, this study aimed to assess the effect of administering vitamin supplementation to sows in gestation and lactation and to their litters on the reproductive performance and body condition of the sows and on the performance and immune profile of the litters until slaughter. The trial was split into two phases. The first phase used 104 sows, assigned to be randomized to blocks according to parity, submitted until 21 days of lactation to two treatments: control–standard (standard levels of vitamins) and test–elevated (elevated levels of vitamins). Each sow and its respective farrow were considered an experimental unit. The sows underwent evaluations of body condition score, back fat thickness and reproductive performance. In the second phase, 60 barrows and 60 gilts at 21 days of age and mean initial weight of 5.33 ± 1.5 kg until slaughter at 164 days of age. The piglets were assigned to randomized blocks according to the weight and sex of the animals in a 2 × 2 factorial model, with 10 replicates per treatment, where a pen with three animals represented the experimental unit. Following the same treatments of the first phase, the piglets were evaluated for daily weight gain, daily feed intake, feed conversion, mortality rate and humoral immune response. Vitamin supplementation had no positive effects on the reproductive parameters or body composition of sows. However, it positively impacted the performance of the litters in the early nursery stage, but did not lead to superior effects on the immune responses to vaccination against circovirus or mycoplasma.
The search for life in the Universe is a fundamental problem of astrobiology and modern science. The current progress in the detection of terrestrial-type exoplanets has opened a new avenue in the characterization of exoplanetary atmospheres and in the search for biosignatures of life with the upcoming ground-based and space missions. To specify the conditions favourable for the origin, development and sustainment of life as we know it in other worlds, we need to understand the nature of global (astrospheric), and local (atmospheric and surface) environments of exoplanets in the habitable zones (HZs) around G-K-M dwarf stars including our young Sun. Global environment is formed by propagated disturbances from the planet-hosting stars in the form of stellar flares, coronal mass ejections, energetic particles and winds collectively known as astrospheric space weather. Its characterization will help in understanding how an exoplanetary ecosystem interacts with its host star, as well as in the specification of the physical, chemical and biochemical conditions that can create favourable and/or detrimental conditions for planetary climate and habitability along with evolution of planetary internal dynamics over geological timescales. A key linkage of (astro)physical, chemical and geological processes can only be understood in the framework of interdisciplinary studies with the incorporation of progress in heliophysics, astrophysics, planetary and Earth sciences. The assessment of the impacts of host stars on the climate and habitability of terrestrial (exo)planets will significantly expand the current definition of the HZ to the biogenic zone and provide new observational strategies for searching for signatures of life. The major goal of this paper is to describe and discuss the current status and recent progress in this interdisciplinary field in light of presentations and discussions during the NASA Nexus for Exoplanetary System Science funded workshop ‘Exoplanetary Space Weather, Climate and Habitability’ and to provide a new roadmap for the future development of the emerging field of exoplanetary science and astrobiology.
The dietary inclusion of feed additives to improve the carcass characteristics of the final product is of great importance for the pork production chain. The aim of our study was to evaluate the effects of the association of ractopamine (RAC) and conjugated linoleic acid (CLA) on the performance traits of finishing pigs during the last 26 days prior to slaughter. In total, 810 commercial hybrid barrows were used. Animals were distributed among treatments according to a randomised block design in a 3 × 3 factorial arrangement, with three RAC levels (0, 5 or 10 ppm) and three CLA levels (0, 0.3 or 0.6%). Pigs fed the diet with 5 ppm RAC had higher average daily feed intake (ADFI) (2.83 kg; P < 0.05) when compared with those fed 10 ppm RAC and the control diet (2.75 and 2.74 kg, respectively). Lower ADFI values (P < 0.01) were observed with the diets containing CLA compared with the control diet with no CLA (2.73 and 2.75 v. 2.85 kg/day, respectively). The average daily weight gain of pigs fed 5 and 10 ppm RAC was +148 and +173 g/dayhigher (P < 0.001), respectively, than those fed the control diet. Dietary RAC levels influenced (P < 0.001) feed conversion ratio (FCR), which was reduced as RAC levels increased, with the pigs fed 10, 5 and 0 ppm RAC presenting FCR values of 2.57, 2.71 and 3.05, respectively. FCR also improved (P < 0.05) with the inclusion of 0.6% CLA relative to the control diet (2.70 v. 2.84, respectively). There was a significant interaction between CLA × RAC levels (P < 0.01) for final BW, loin eye area (LEA) (P < 0.05) and backfat thickness (BT) (P < 0.05). The treatments containing 10 ppm RAC + 0.6% or 0.3% CLA increased LEA and reduced BT. In conclusion, the level of 10 ppm inclusion of RAC increased the overall performance parameters of pigs and therefore improved production efficiency. The combined use of RAC and CLA promoted a lower feed conversion ratio as well as better quantitative carcass traits, as demonstrated by the higher LEA and lower BT. The dietary inclusion of CLA at 0.3% improved feed efficiency, however, without affecting LEA or BT yields.
The enrichment of meat with selenium is important to improve the intake of selenium by humans. The effects of supranutritional doses of sodium selenite or selenium-enriched yeast on performance, carcass characteristics and meat quality were evaluated using 63 Nellore cattle in a completely randomized design with two sources (sodium selenite and selenium-enriched yeast), three levels (0.3, 0.9 and 2.7 mg Se/kg DM) and control treatment (without addition of selenium). Final body weight (BW), average daily gain, dry matter intake and gain to feed ratio (G : F) at the end of 84 days of supplementation were not influenced by treatments (P>0.05). Values of pH, ribeye area, back fat thickness and marbling score were also not influenced by treatments (
P>0.05). Dressing percentage was greater (P=0.02) in Nellore cattle supplemented with organic Se (58.70%) compared to animals supplemented with inorganic Se (57.94%). Hot carcass weight increased (
P=0.05) with the increasing of Se levels in the diet. Colour, shear force (SF), cooking and drip loss remained unchanged (
P>0.05); however thiobarbituric acid reactive substances was 15.51% higher with inorganic Se compared with organic Se. The selenium concentration in the meat of animals receiving organic selenium was higher (
P<0.001) than that of animals receiving sodium selenite, at all levels (0.3; 0.9 and 2.7 mg/kg DM). The meat of animals receiving 2.7 mg of organic Se/kg of DM presented concentration of 372.7 μg Se/kg in the L.dorsi muscle, and the intake of 150 g of this meat by humans provides approximately 100% of the recommended Se intake (55 μg Se/day for adults). Therefore, the use of supranutritional doses of 2.7 mg Se/kg of DM, regardless of source, is a way of naturally producing selenium-enriched meat without compromising performance, carcass characteristics and quality of Nellore bovine meat.
Tuberculosis (TB) is the leading cause of death among infectious diseases worldwide. Among the estimated cases of drug-resistant TB, approximately 60% occur in the BRICS countries (Brazil, Russia, India, China and South Africa). Among Brazilian states, primary and acquired multidrug-resistant TB (MDR-TB) rates were the highest in Rio Grande do Sul (RS). This study aimed to perform molecular characterisation of MDR-TB in the State of RS, a high-burden Brazilian state. We performed molecular characterisation of MDR-TB cases in RS, defined by drug susceptibility testing, using 131 Mycobacterium tuberculosis (M.tb) DNA samples from the Central Laboratory. We carried out MIRU-VNTR 24loci, spoligotyping, sequencing of the katG, inhA and rpoB genes and RDRio sublineage identification. The most frequent families found were LAM (65.6%) and Haarlem (22.1%). RDRio deletion was observed in 42 (32%) of the M.tb isolates. Among MDR-TB cases, eight (6.1%) did not present mutations in the studied genes. In 116 (88.5%) M.tb isolates, we found mutations associated with rifampicin (RIF) resistance in rpoB gene, and in 112 isolates (85.5%), we observed mutations related to isoniazid resistance in katG and inhA genes. An insertion of 12 nucleotides (CCAGAACAACCC) at the 516 codon in the rpoB gene, possibly responsible for a decreased interaction of RIF and RNA polymerase, was found in 19/131 of the isolates, belonging mostly to LAM and Haarlem families. These results enable a better understanding of the dynamics of transmission and evolution of MDR-TB in the region.
Major depressive disorder (MDD) is a multifactorial syndrome with significant interactions between genetic and environmental factors. This study specifically investigates the association between family history of alcohol problems (FHAP) and family history of depression (FHD), and how these relate to different clusters of depressive symptoms.
Correlations between FHAP and FHD and different clusters of the Beck Depression Inventory (BDI) were studied. We sampled 333 employees from a general hospital who had been receiving a psychiatric consultation between 2005 and 2012. Analysis of variance (ANOVA) and Analysis of covariance (ANCOVA) models were conducted to explore these correlations.
There was a significant positive correlation between FHAP and BDI affective score. This result remained significant even after the adjustment for other variables considered as important factors for MDD, such as gender, age, marital status, education, ethnic group and FHD. More specifically, FHAP was correlated with dissatisfaction and episodes of crying among the affective symptoms. FHAP showed no statistical difference in any of the other clusters score or in the BDI total score. Moreover, as expected, we found a correlation between FHD and BDI total score and Somatic and Cognitive clusters.
FHAP should be routinely investigated in individuals presenting with depressive symptoms. This is especially important in cases presenting with dissatisfaction and episodes of crying in patients who do not endorse criteria for MDD. Due to study limitations, the findings require replication by neurobiological, epidemiological and clinical studies.
Intake in sugar-rich diets can be limited either via rumen fill or excessive rumen fermentation and source of non-fibre carbohydrate (NFC) in the diet can affect both factors. The aim of the current study was to quantify the effect of partially replacing ground maize (GM) with steam-rolled maize (SRM) or pelleted citrus pulp (PCP) at two concentrate levels in sugarcane-based diets on digestibility, rumen ecosystem and metabolism of Nellore steers. Six rumen-cannulated steers were assigned to a 6 × 6 Latin square, replicated in time, in a 2 × 3 factorial arrangement of treatments with two levels of concentrate (600 or 800 g concentrate/kg dry matter [DM]) and three NFC sources. Each steer within a period was considered an experimental unit. Feeding more concentrate increased total tract digestibility of organic matter and decreased fibre intake and passage rate. It also reduced rumen populations of Fibrobacter succinogenes and Streptococcus bovis and increased Ruminococcus flavefaciens. Substituting PCP for GM increased rumen pH, acetic acid and organic matter digestibility. Feeding PCP also reduced R. flavefaciens and R. amylophilus rumen populations. Substituting SRM for GM increased starch digestibility and rumen propionic acid, but decreased rumen ammonia concentration. Feeding SRM increased rumen populations of Megasphaera elsdenii with the high-concentrate diet but reduced Ruminococcus albus populations at both concentrate levels. In conclusion, partial replacement of GM by PCP decreased intake in sugar-rich diets, while increasing total tract neutral detergent fibre digestibility. Replacement of GM with SRM increases rumen fermentation and total tract digestibility of starch.
The use of tail chalk and estrus/heat expression scores (HEATSC) evaluation is instrumental in identifying cows with greater estrus expression and greater artificial insemination pregnancy rates (P/AI) in cows submitted to timed artificial insemination (TAI), and cows with low or no estrus expression present lower P/AI. It was intended in this study to improve the pregnancy rates in TAI for Bos indicus beef cows, and gonadotrophin-releasing hormone (GnRH) injection was hypothesized to increase pregnancy rates in a TAI program for cows submitted to progesterone–estradiol-based protocols with low or no estrus expression, evaluated by HEATSC. Cows (n= 2284) received a progesterone device and 2 mg estradiol benzoate, after 8 days the device was removed and 1 mg estradiol cypionate, 150 μg of d-cloprostenol and 300 IU equine chorionic gonadotropin was administered. All cows were marked with chalk and HEATSC evaluated (scales 1 to 3) at TAI performed on day 10. Animals with HEATSC1 and HEATSC2 (n= 937) received 100 μg de gonadorelin (GNRH group; n= 470), or 1 ml saline (Control group; n= 467), and cows with HEATSC3 (named HEAT group; n= 1347) received no additional treatment. The larger dominant follicle, evaluated on day 8and at TAI (day 10), was greater in HEAT group (P= 0.0145 and P <0.001, respectively). Corpus luteum (CL) area and progesterone concentration was evaluated on day 17, and CL area was larger in HEAT group, intermediary in Control and lower in GnRH group (Control= 2.68 cm2, GnRH= 2.37 cm2, HEAT group= 3.07 cm2, P <0.001). Greater progesterone concentrations were found in HEAT group than in Control and GnRH groups (Control= 4.74 ng/ml, GnRH= 4.29 ng/ml, HEAT group= 6.08 ng/ml, P<0.001). There was a difference in ovulation rate, greater in HEAT group than GnRH and Control groups (Control= 72.5%; GnRH= 81.25%; HEAT group= 90.71%; P= 0.0024). Artificial insemination pregnancy rates was greater in HEAT group (57.09% (769/1347) than in Control and GNRH groups, with positive effect of GnRH injection at the time of TAI in P/AI (Control= 36.18% (169/467), GnRH= 45.95% (216/470); P<0.0001). In conclusion, GnRH application in cows with low HEATSC (1 and 2) is a simple strategy, requiring no changes in TAI management to increase pregnancy rates in postpartum beef cows submitted to progesterone–estradiol-based TAI protocols, without reaching, however, the pregnancy rates of cows that demonstrate high estrus expression at the TAI.
This paper describes a model of electron energization and cyclotron-maser emission applicable to astrophysical magnetized collisionless shocks. It is motivated by the work of Begelman, Ergun and Rees [Astrophys. J. 625, 51 (2005)] who argued that the cyclotron-maser instability occurs in localized magnetized collisionless shocks such as those expected in blazar jets. We report on recent research carried out to investigate electron acceleration at collisionless shocks and maser radiation associated with the accelerated electrons. We describe how electrons accelerated by lower-hybrid waves at collisionless shocks generate cyclotron-maser radiation when the accelerated electrons move into regions of stronger magnetic fields. The electrons are accelerated along the magnetic field and magnetically compressed leading to the formation of an electron velocity distribution having a horseshoe shape due to conservation of the electron magnetic moment. Under certain conditions the horseshoe electron velocity distribution function is unstable to the cyclotron-maser instability [Bingham and Cairns, Phys. Plasmas 7, 3089 (2000); Melrose, Rev. Mod. Plasma Phys. 1, 5 (2017)].
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 mechanisms involved in kidney disturbances during development, induced by vitamin D3 deficiency in female rats, that persist into adulthood were evaluated in this study. Female offspring from mothers fed normal (control group, n=8) or vitamin D-deficient (Vit.D-, n=10) diets were used. Three-month-old rats had their systolic blood pressure (SBP) measured and their blood and urine sampled to quantify vitamin D3 (Vit.D3), creatinine, Na+, Ca+2 and angiotensin II (ANGII) levels. The kidneys were then removed for nitric oxide (NO) quantification and immunohistochemical studies. Vit.D- pups showed higher SBP and plasma ANGII levels in adulthood (P<0.05) as well as decreased urine osmolality associated with increases in urinary volume (P<0.05). Decreased expression of JG12 (renal cortex and glomeruli) and synaptopodin (glomeruli) as well as reduced renal NO was also observed (P<0.05). These findings showed that renal disturbances in development in pups from Vit.D- mothers observed in adulthood may be related to the development of angiogenesis, NO and ANGII alterations.
Protein is the most costly nutrient in fish feed, and while diets offered in the early stages of development typically have high levels of CP, they do not always correspond to the real requirements of the animals. Thus, research that seeks to learn the true nutritional requirements of fish is fundamental to improving commercial fish culture. The present study evaluated the protein requirements of Nile tilapia (Oreochromis niloticus) under larviculture. Fish performance, gene expression for digestive enzymes and their enzymatic activity and stress response to air exposure were analyzed. Four experimental diets differing in CP level were formulated: 30%, 36%, 42% and 48%. Fish larvae were fed the experimental diets during development and sampled 10, 20 and 30 days after the beginning of the experiment for performance, gene expression and enzymatic activity. At sampling time 30, stress resistance was also evaluated by means of an air exposure test. At sampling time 10, CP levels between 36% and 48% could be used for a better performance. During this period, pepsinogen expression was greater for 30% CP, intermediate for 42% and lower for 36% and 48%. After this initial period, diets of between 30% and 42% CP are recommended for better performance. At sampling time 20, gene expression for digestive enzymes and their enzymatic activity were similar for all diets tested. At sampling time 30, the diet of 42% CP induced both greater pepsinogen expression and pepsin activity. Survival after the air exposure test after 30 days of feeding was influenced by CP level in the diet, with the highest survival being for fish fed with 36% CP. Taken together, the present results demonstrate that dietary CP influences digestive enzyme gene expression and activity, and suggest that the best CP levels for Nile tilapia larviculture vary depending on larval stage.