Post-harvest quality of melon accessions subjected to salinity.

The objective was to evaluate the behavior of melon genotypes (Cucumis melo L.) in the physical, chemical and biochemical quality of melon fruits as a function of electrical conductivity irrigation water levels (ECw). The experimental design adopted was randomized blocks in a 5 x 3 factorial scheme with five replications. The first factor was represented by five salinity levels (0.5, 1.5, 3.0, 4.5, and 6.0 dS m-1) and the second factor by accessions A35, and A24, and the hybrid Sancho. The physical, chemical and biochemical variables showed a reduction in production, with smaller fruits, with less weight, smaller cavity, with increased pulp thickness for Sancho. Vitamin C and yellow flavonoids increased indicating antioxidant power against ROS. The genotypes showed similar post-harvest behavior, however, the hybrid Sancho stood out over the others, possibly because it is an improved material. Accession A24 presented physiological and biochemical responses that classify it as intolerant.

Evaluating total nitrogen and phosphorous concentrations in a watershed impacted by diverse anthropic activities in a developing country.

This research aims to identify critical contamination points by nutrients, their possible origin (point and nonpoint sources), their spatial distribution, and possible attenuation by natural and anthropogenic processes. The study area is the Velhas River Basin, located in the Southeast Region of Brazil (17.0°-20.5° S; 43.5°-45.0°W). A historical series of water quality monitoring, land cover map, demographic and agricultural censuses, sewage treatment diagnostics, and local hydrographic networks were used to achieve the objectives. In addition, the regions were divided into incremental areas, enabling individualized analyses of each sub-basin. Descriptive statistics, seasonality, categorized data tests, agglomerative hierarchical cluster analysis, and principal component analysis were used. There was a significant contribution of nutrients in the most important urban agglomeration of the basin, resulting in peak concentrations measured at that place. Although the values were reduced by the mouth (650 km), the percentage of legislation violations remained high. The effects of punctual contamination were intensified by the low percentage of treated sewage in the basin, the absence of adequate treatment technologies to remove nutrients, and the disorderly urbanization. Furthermore, it was estimated that the nutrient load from animal husbandry is approximately 75% of the load from domestic effluents due to the high number of cattle in the basin and the low percentage of forests.

A Case Report on Pseudo-Internuclear Ophthalmoplegia: A Rare Manifestation of Myasthenia Gravis.

A 41-year-old male with recently diagnosed diabetes mellitus type 2 presented with drooping of the left eyelid with double vision and was found to have an adduction deficit in the left eye and nystagmus in the abducting right eye during conjugated gaze: a left-sided internuclear ophthalmoplegia (INO). A medial longitudinal fasciculus (MLF) lesion was excluded exhaustively with brain imaging. The possibility of a pseudo-INO was considered. The autoantibody profile demonstrated positivity to acetylcholine receptor (AChR) antibody. Repetitive nerve stimulation (RNS) and electromyography (EMG) were unremarkable. An acetylcholinesterase inhibitor trial showed a significant improvement in the ocular symptoms. Hence, the diagnosis of ocular myasthenia was confirmed. There was no evidence of a thymic hyperplasia. Herein, we discuss pseudo-INO being an atypical presentation of myasthenia gravis (MG), emphasizing the importance of having a strong suspicion despite unremarkable test results.

A Case Report of Takotsubo Cardiomyopathy With Dengue.

A 74-year-old woman with well-controlled hypertension and dyslipidemia with acute fever was diagnosed with dengue infection. She had non-anginal central chest pain which was associated with ST elevation and T inversions in V1 to V6 with prolonged QT interval. Her high-sensitivity troponin was elevated. There was echocardiographic evidence of severe left ventricular dysfunction (ejection fraction 35%; Simpson method) with apical ballooning suggestive of takotsubo cardiomyopathy. No left ventricular basal hyperkinesia was noted. The patient was managed as per the national dengue guidelines of Sri Lanka. Her cardiac condition was managed conservatively. She did not experience dengue complications such as dengue shock syndrome or dengue hemorrhagic fever or pulmonary edema secondary to severe LV dysfunction. The clinical symptoms and echocardiographic findings of takotsubo cardiomyopathy resolved parallel to dengue fever.

Efficacy of resveratrol in male urogenital tract dysfunctions: an evaluation of pre-clinical data.

Resveratrol is a polyphenol found naturally in fruits and plants. Recently, studies in humans and animal models have suggested beneficial properties of this polyphenol, such as improvements to metabolic and lipid profiles, along with antioxidant, anti-inflammatory and anti-proliferative effects. In the urogenital tract (UGT), resveratrol has also been tested clinically and experimentally as a therapeutic drug in several diseases; however, the translational efficacy of resveratrol, especially in UGT, is still a matter of debate. In the present review, we address the pre-clinical efficacy of resveratrol in UGT-related dysfunctions, focusing on lower urinary tract symptoms, non-cancerous prostatic disease (benign prostatic hyperplasia and prostatitis) and erectile dysfunction. In vitro studies indicate that resveratrol reduces inflammatory markers and oxidative stress, and improves endothelial function in UGT organs and cells isolated from humans and animals. Despite displaying low oral bioavailability, in vivo administration of resveratrol largely improves erectile dysfunction, benign prostatic hyperplasia, prostatitis and voiding impairments, as evidenced in different animal models. Resveratrol also acts as a microbiota modulator, which may explain some of its beneficial effects in vivo. In contrast to the large amount of pre-clinical data, there are insufficient clinical trials to establish resveratrol treatment efficacy in human UGT-related diseases. In summary, we provide an overview of the in vivo and in vitro efficacy of resveratrol in animal and human UGT dysfunctions, which may support future clinical trials.

Rhinocerebral Mucormycosis with Extensive Cranial Nerve Palsies in a Diabetic Patient.

Mucormycosis is a common opportunistic fungal infection with a disseminated nature. Despite being a devastating disease with the involvement of multiple upper cranial nerves, the implications of the seventh cranial nerve have been infrequently encountered. Although the radiological evidence with sinus destruction supports the diagnosis, histological specimen showing fungal elements confirms it as fungal culture doesn't always demonstrate a high diagnostic yield. Early detection and multimodal treatment are mandatory to prevent detrimental outcomes and to control the disease progression. We, hereby present a rare case of rhinocerebral mucormycosis with multiple cranial nerve involvement including the facial nerve in a 70-year-old female with long-standing poorly controlled diabetes mellitus.

Melioidosis with a subdural collection - a case report.

BACKGROUND: Melioidosis is an infection caused by Burkholderia pseudomallei, which is more prevalent in the tropics and leads to significant morbidity and mortality. It characteristically produces widespread caseous lesions and abscesses, and can present with varied clinical manifestations. Melioidosis involving the central nervous system is uncommon. CASE PRESENTATION: A 42-year-old Sri Lankan male with type 2 diabetes presented with a febrile illness of 6 days with headache and constitutional symptoms. Clinical examination was unremarkable. Four days later, he developed focal seizures involving the left leg and numbness of the left side. Initial laboratory investigations were suggestive of a bacterial infection. Blood culture was reported as positive for a Pseudomonas species, which was resistant to gentamicin. Contrast enhanced CT and MRI scans of the brain showed a subdural collection in the right fronto-temporo-parietal region with possible abscess formation. Melioidosis antibody testing using indirect hemagglutination method was reactive with a titre more than 1/10,240. He was treated with intravenous meropenem and oral co-trimoxazole for 8 weeks (Intensive phase). The subdural collection was managed conservatively, and seizures were treated with oral antiepileptics. At 7 weeks, follow-up contrast enhanced MRI showed improvement of the subdural collection, and inflammatory markers had normalized. He was discharged after 8 weeks, and treated with oral co-trimoxazole and doxycycline for 6 months (eradication phase). At 6 months follow-up, the patient is asymptomatic. CONCLUSIONS: Cerebral melioidosis is an unusual presentation of melioidosis where the diagnosis can be easily missed. Knowledge of the protean manifestations of melioidosis is of paramount importance in order to detect and treat this potentially fatal infection appropriately, especially in tropical countries where the disease is endemic.

Testosterone replacement in transgenic sickle cell mice controls priapic activity and upregulates PDE5 expression and eNOS activity in the penis.

Sickle cell disease (SCD)-associated priapism is characterized by decreased nitric oxide (NO) signaling and downregulated phosphodiesterase (PDE)5 protein expression and activity in the penis. Priapism is also associated with testosterone deficiency, but molecular mechanisms underlying testosterone effects in the penis in SCD are not known. Given the critical role of androgens in erection physiology and NO synthase (NOS)/PDE5 expression, we hypothesized that testosterone replacement to eugonadal testosterone levels reduces priapism by reversing impaired endothelial (e)NOS activity and molecular abnormalities involving PDE5. Adult male transgenic Berkeley sickle cell (Sickle) and wild-type (WT) mice were implanted with testosterone pellets, which release 1.2 µg testosterone/day for 21 days, or vehicle. After 21 days, animals underwent erectile function assessment followed by collection of blood for serum testosterone measurements, penes for molecular analysis, and seminal vesicles as testosterone-responsive tissue. Serum testosterone levels were measured by radioimmunoassay; protein expressions of PDE5, α-smooth muscle actin, eNOS and nNOS, and phosphorylation of PDE5 at Ser-92, eNOS at Ser-1177, neuronal (n) NOS at Ser-1412, and Akt at Ser-473 were measured by Western blot in penile tissue. Testosterone treatment reversed downregulated serum testosterone levels and increased (p < 0.05) the weight of seminal vesicles in Sickle mice to levels comparable to that of WT mice, indicating restored testosterone levels in Sickle mice. Testosterone treatment reduced (p < 0.05) prolonged detumescence in Sickle mice and normalized downregulated P-PDE5 (Ser-92), PDE5, P-eNOS (Ser-1177), and P-Akt (Ser-473) protein expressions in the Sickle mouse penis. Testosterone treatment did not affect P-nNOS (Ser-1412), eNOS, nNOS, or α-smooth muscle actin protein expressions in the Sickle mouse penis. In conclusion, in the mouse model of human SCD, increasing testosterone to eugonadal levels reduced priapic activity and reversed impaired Akt/eNOS activity and PDE5 protein expression in the penis.

Indices estimated using REML/BLUP and introduction of a super-trait for the selection of progenies in popcorn.

Selection indices commonly utilize economic weights, which become arbitrary genetic gains. In popcorn, this is even more evident due to the negative correlation between the main characteristics of economic importance - grain yield and popping expansion. As an option in the use of classical biometrics as a selection index, the optimal procedure restricted maximum likelihood/best linear unbiased predictor (REML/BLUP) allows the simultaneous estimation of genetic parameters and the prediction of genotypic values. Based on the mixed model methodology, the objective of this study was to investigate the comparative efficiency of eight selection indices estimated by REML/BLUP for the effective selection of superior popcorn families in the eighth intrapopulation recurrent selection cycle. We also investigated the efficiency of the inclusion of the variable "expanded popcorn volume per hectare" in the most advantageous selection of superior progenies. In total, 200 full-sib families were evaluated in two different areas in the North and Northwest regions of the State of Rio de Janeiro, Brazil. The REML/BLUP procedure resulted in higher estimated gains than those obtained with classical biometric selection index methodologies and should be incorporated into the selection of progenies. The following indices resulted in higher gains in the characteristics of greatest economic importance: the classical selection index/values attributed by trial, via REML/BLUP, and the greatest genotypic values/expanded popcorn volume per hectare, via REML. The expanded popcorn volume per hectare characteristic enabled satisfactory gains in grain yield and popping expansion; this characteristic should be considered super-trait in popcorn breeding programs.

Genetic control and combining ability of agronomic attributes and northern leaf blight-related attributes in popcorn.

The present study was conducted to investigate the genetic control and to estimate the general and specific combining abilities of popcorn for agronomic attributes and attributes related to resistance to northern leaf blight (NLB). The 56 hybrids (F1 and reciprocals), together with the eight parent lines and six controls, were evaluated in two harvests, in a randomized-block design with four replications. Dominance components were more expressive than the additive components for grain yield and expression of resistance, and hybridization was the most suitable option for obtaining resistant and productive genotypes. For grain yield, popping expansion, and resistance to NLB, there was no significance for reciprocal effects, which indicates that the direction in which the cross is performed does not interfere with the hybrid's performance. Then, the superior hybrids recommended for more profitable growth were P8 x L61, L61 x L76, and L61 x L77.

1H, 15N and 13C resonance assignments of Ixolaris, a tissue factor pathway inhibitor from the tick salivary gland.

Ixolaris is a two-Kunitz tick salivary gland protein identified in Ixodes scapularis that presents sequence homology to TFPI (tissue factor pathway inhibitor). It binds to the coagulation enzyme factor Xa (FXa) or to its zymogen form, FX, and further inhibits tissue factor/FVIIa complex (extrinsic Xnase compex). Differently from TFPI, Ixolaris does not bind to the active site cleft of FXa. Instead, complex formation is mediated by the FXa heparin-binding exosite, which may also results in decreased FXa activity into the prothrombinase complex. The Ixolaris-FXa/FX complex formation has been characterized by using a combination of biophysical and biochemical technics although no structural data is currently available. In this study, we reported the NMR chemical shift assignment of Ixolaris, as a first step to further establishing the structure, dynamics and function relationship for this protein.

Recombinant expression of Ixolaris, a Kunitz-type inhibitor from the tick salivary gland, for NMR studies.

Ixolaris is an anticoagulant protein identified in the tick saliva of Ixodes scapularis. Ixolaris contains 2 Kunitz like domains and binds to Factor Xa or Factor X as a scaffold for inhibition of the Tissue Factor (TF)/Factor VIIa (FVIIa). In contrast to tissue factor pathway inhibitor (TFPI), however, Ixolaris does not bind to the active site cleft of FXa. Instead, complex formation is mediated by the FXa heparin-binding exosite. Due to its potent and long-lasting antithrombotic activity, Ixolaris is a promising agent for anticoagulant therapy. Although numerous functional studies of Ixolaris exist, three-dimensional structure of Ixolaris has not been obtained at atomic resolution. Using the pET32 vector, we successfully expressed a TRX-His6-Ixolaris fusion protein. By combining Ni-NTA chromatography, enterokinase protease cleavage, and reverse phase HPLC (RP-HPLC), we purified isotopically labeled Ixolaris for NMR studies. 1D 1H and 2D 15N-1H NMR analysis yielded high quality 2D 15N-1H HSQC spectra revealing that the recombinant protein is folded. These studies represent the first steps in obtaining high-resolution structural information by NMR for Ixolaris enabling the investigation of the molecular basis for Ixolaris-coagulation factors interactions.

Extended spectrum beta lactamase producing organisms causing urinary tract infections in Sri Lanka and their antibiotic susceptibility pattern -A hospital based cross sectional study.

BACKGROUND: Extended Spectrum Beta- Lactamase producing organisms causing urinary tract infections (ESBL-UTI) are increasing in incidence and pose a major burden to health care. While ESBL producing Klebsiella species seem to account for most nosocomial outbreaks, ESBL-producing E. coli have been isolated from both hospitalized and non-hospitalized patients. Although 95-100% ESBL organisms are still considered sensitive to meropenem, rapid emergence of carbapenem resistance has been documented in many countries. The objective of this study was to evaluate urinary tract infections caused by ESBL producers and the antibiotic susceptibility patterns in Sri Lanka. METHODS: Patients with confirmed ESBL-UTI admitted to Professorial Medical Unit, Colombo North Teaching Hospital from January - June 2015 were recruited to the study. Their urine culture and antibiotic susceptibility reports were evaluated after obtaining informed written consent. RESULTS: Of 61 culture positive ESBL-UTIs, E. coli caused 53 (86.8%), followed by Klebsiella in 8 (13.1%).30 (49.1%) had a history of hospitalization within the past three months and included 6/8(75%) of Klebsiella UTI and 24/53(45.2%) of E.coli UTI. Antibiotic susceptibility of ESBL organisms were; Meropenem 58 (95%), Imipenem 45 (73.7%), Amikacin 37 (60.6%) and Nitrofurantoin 28(45.9%). In 3(4.9%), E.coli were resistant to Meropenem. These three patients had received multiple antibiotics including meropenem in the recent past for recurrent UTI. CONCLUSIONS: We observed a higher percentage of E. coli over Klebsiella as ESBL producing organisms suggesting most ESBL-UTIs to be community acquired, Carbapenems seem to remain as the first line therapy for majority of ESBL-UTIs in the local setting. However 4.9% prevalence of meropenem resistance is alarming compared to other countries. Although prior antibiotic utilization and hospitalization may contribute to emergence of ESBL producing Klebsiella and E.coli in Sri Lanka, high prevalence of community acquired ESBL-E. coli needs further investigations to identify potential causes . Being a third world country with a free health care system, observed alarming rate of carbapenem resistance is likely to add a significant burden to health budget. We feel that treatment of infections in general needs a careful approach adhering to recommended antibiotic guidelines in order to prevent emergence of multi drug resistant organisms.

Antitrypanosomal Activity of Sterol 14α-Demethylase (CYP51) Inhibitors VNI and VFV in the Swiss Mouse Models of Chagas Disease Induced by the Trypanosoma cruzi Y Strain.

Chagas disease is a life-threatening infection caused by a variety of genetically diverse strains of the protozoan parasite Trypanosoma cruzi The current treatment (benznidazole and nifurtimox) is unsatisfactory, and potential alternatives include inhibitors of sterol 14α-demethylase (CYP51), the cytochrome P450 enzyme essential for the biosynthesis of sterols in eukaryotes and the major target of clinical and agricultural antifungals. Here we performed a comparative investigation of two protozoon-specific CYP51 inhibitors, VNI and its CYP51 structure-based derivative VFV, in the murine models of infection caused by the Y strain of T. cruzi The effects of different treatment regimens and drug delivery vehicles were evaluated in animals of both genders, with benznidazole serving as the reference drug. Regardless of the treatment scheme or delivery vehicle, VFV was more potent in both genders, causing a >99.7% peak parasitemia reduction, while the VNI values varied from 91 to 100%. Treatments with VNI and VFV resulted in 100% animal survival and 0% natural relapse after the end of therapy, though, except for the 120-day treatment schemes with VFV, relapses after three cycles of immunosuppression were observed in each animal group, and quantitative PCR analysis revealed a very light parasite load in the blood samples (sometimes below or near the detection limit, which was 1.5 parasite equivalents/ml). Our studies support further investigations of this class of compounds, including their testing against other T. cruzi strains and in combination with other drugs.

Multivariate approach in popcorn genotypes using the Ward-MLM strategy: morpho-agronomic analysis and incidence of Fusarium spp.

The multivariate analyses are useful tools to estimate the genetic variability between accessions. In the breeding programs, the Ward-Modified Location Model (MLM) multivariate method has been a powerful strategy to quantify variability using quantitative and qualitative variables simultaneously. The present study was proposed in view of the dearth of information about popcorn breeding programs under a multivariate approach using the Ward-MLM methodology. The objective of this study was thus to estimate the genetic diversity among 37 genotypes of popcorn aiming to identify divergent groups associated with morpho-agronomic traits and traits related to resistance to Fusarium spp. To this end, 7 qualitative and 17 quantitative variables were analyzed. The experiment was conducted in 2014, at Universidade Estadual do Norte Fluminense, located in Campos dos Goytacazes, RJ, Brazil. The Ward-MLM strategy allowed the identification of four groups as follows: Group I with 10 genotypes, Group II with 11 genotypes, Group III with 9 genotypes, and Group IV with 7 genotypes. Group IV was distant in relation to the other groups, while groups I, II, and III were near. The crosses between genotypes from the other groups with those of group IV allow an exploitation of heterosis. The Ward-MLM strategy provided an appropriate grouping of genotypes; ear weight, ear diameter, and grain yield were the traits that most contributed to the analysis of genetic diversity.

Interaction of nucleus reuniens and entorhinal cortex projections in hippocampal field CA1 of the rat.

The nucleus reuniens (RE) and entorhinal cortex (EC) provide monosynaptic excitatory inputs to the apical dendrites of pyramidal cells and to interneurons with dendrites in stratum lacunosum moleculare (LM) of hippocampal field CA1. However, whether the RE and EC inputs interact at the cellular level is unknown. In this electrophysiological in vivo study, low-frequency stimulation was used to selectively activate each projection at its origin; field excitatory postsynaptic potentials (fEPSPs) were recorded in CA1. We applied (1) paired pulses to RE or EC, (2) combined paired pulses to RE and EC, and (3) simultaneously paired pulses to RE/EC. The main findings are that: (a) stimulation of either RE- or EC-evoked subthreshold fEPSPs, displaying paired pulse facilitation (PPF), (b) subthreshold fEPSPs evoked by combined stimulation did not display heterosynaptic PPF, and (c) simultaneous stimulation of RE/EC resulted in enhanced subthreshold fEPSPs in proximal LM displaying a nonlinear interaction. CSD analyses of RE/EC-evoked depth profiles revealed a nonlinear enlargement of the 'LM sink-radiatum source' configuration and the appearance of an additional small sink-source pair close to stratum pyramidale, likely reflecting (peri)somatic inhibition. The nonlinear interaction between both inputs indicates that RE and EC axons form synapses, at least partly, onto the same dendritic compartments of CA1 pyramidal cells. We propose that low-frequency activation of the RE-CA1 input facilitates the entorhinal-hippocampal dialogue, and may synchronize the neocortical-hippocampal slow oscillation which is relevant for hippocampal-dependent memory consolidation.

Proposal of a super trait for the optimum selection of popcorn progenies based on path analysis.

A challenge faced by popcorn breeding programs is the existence of a negative correlation between the two main traits, popping expansion and yield, which hinders simultaneous gains. The objective of this study was to investigate the use of a new variable or super trait, which favors the reliable selection of superior progenies. The super trait 'expanded popcorn volume per hectare' was introduced in the evaluation of 200 full-sib families of the eighth recurrent intrapopulation selection cycle, which were arranged in randomized blocks with three replicates in two environments. Although the inability to obtain simultaneous gains through selection via popping expansion or yield was confirmed, the super trait was positively associated with both yield and popping expansion, allowing simultaneous gains via indirect selection using 'expanded popcorn volume per hectare' as the main trait. This approach is recommended because this super trait can be used in breeding programs to optimize selective gains for the crop.

In Vitro and In Vivo Trypanosomicidal Action of Novel Arylimidamides against Trypanosoma cruzi.

Arylimidamides (AIAs) have been shown to have considerable biological activity against intracellular pathogens, includingTrypanosoma cruzi, which causes Chagas disease. In the present study, the activities of 12 novel bis-AIAs and 2 mono-AIAs against different strains ofT. cruziin vitroandin vivowere analyzed. The most active wasm-terphenyl bis-AIA (35DAP073), which had a 50% effective concentration (EC50) of 0.5 µM for trypomastigotes (Y strain), which made it 26-fold more effective than benznidazole (Bz; 13 µM). It was also active against the Colombiana strain (EC50= 3.8 µM). Analysis of the activity against intracellular forms of the Tulahuen strain showed that this bis-AIA (EC50= 0.04 µM) was about 100-fold more active than Bz (2 µM). The trypanocidal effect was dissociated from the ability to trigger intracellular lipid bodies within host cells, detected by oil red labeling. Both an active compound (35DAP073) and an inactive compound (26SMB060) displayed similar activation profiles. Due to their high selectivity indexes, two AIAs (35DAP073 and 35DAP081) were moved toin vivostudies, but because of the results of acute toxicity assays, 35DAP081 was excluded from the subsequent tests. The findings obtained with 35DAP073 treatment of infections caused by the Y strain revealed that 2 days of therapy induced a dose-dependent action, leading to 96 to 46% reductions in the level of parasitemia. However, the administration of 10 daily doses in animals infected with the Colombiana strain resulted in toxicity, preventing longer periods of treatment. The activity of the combination of 0.5 mg/kg of body weight/day 35DAP073 with 100 mg/kg/day Bz for 10 consecutive days was then assayed. Treatment with the combination resulted in the suppression of parasitemia, the elimination of neurological toxic effects, and survival of 100% of the animals. Quantitative PCR showed a considerable reduction in the parasite load (60%) compared to that achieved with Bz or the amidine alone. Our results support further investigations of this class with the aim of developing novel alternatives for the treatment of Chagas disease.

Mirabegron relaxes urethral smooth muscle by a dual mechanism involving ß3 -adrenoceptor activation and α1 -adrenoceptor blockade.

LINKED ARTICLE: This article is commented on by Michel, M. C., pp. 429-430 of this issue. To view this commentary visit http://dx.doi.org/10.1111/bph.13379. BACKGROUND AND PURPOSE: Mirabegron is the first ß3 -adrenoceptor agonist approved for treatment of overactive bladder syndrome. This study aimed to investigate the effects of ß3 -adrenoceptor agonist mirabegron in mouse urethra. The possibility that mirabegron also exerts α1 -adrenoceptor antagonism was also tested in rat smooth muscle preparations presenting α1A - (vas deferens and prostate), α1D - (aorta) and α1B -adrenoceptors (spleen). EXPERIMENTAL APPROACH: Functional assays were carried out in mouse and rat isolated tissues. Competition assays for the specific binding of [(3) H]prazosin to membrane preparations of HEK-293 cells expressing each of the human α1 -adrenoceptors, as well as ß-adrenoceptor mRNA expression and cyclic AMP measurements in mouse urethra, were performed. KEY RESULTS: Mirabegron produced concentration-dependent urethral relaxations that were shifted to the right by the selective ß3 -adrenoceptor antagonist L-748,337 but unaffected by ß1 - and ß2 -adrenoceptor antagonists (atenolol and ICI-118,551 respectively). Mirabegron-induced relaxations were enhanced by the PDE4 inhibitor rolipram, and the agonist stimulated cAMP synthesis. Mirabegron also produced rightward shifts in urethral contractions induced by the α1 -adrenoceptor agonist phenylephrine. Schild regression analysis revealed that mirabegron behaves as a competitive antagonist of α1 -adrenoceptors in urethra, vas deferens and prostate (α1A -adrenoceptor, pA2  â‰… 5.6) and aorta (α1D -adrenoceptor, pA2  â‰… 5.4) but not in spleen (α1B -adrenoceptor). The affinities estimated for mirabegron in functional assays were consistent with those estimated in radioligand binding with human recombinant α1A - and α1D -adrenoceptors (pKi  â‰… 6.0). CONCLUSION AND IMPLICATIONS: The effects of mirabegron in urethral smooth muscle are the result of ß3 -adrenoceptor agonism together with α1A and α1D -adrenoceptor antagonism.

Resource availability and diet in Harpy Eagle breeding territories on the Xingu River, Brazilian Amazon.

In the Tapajos-Xingu interfluve, one of the largest birds of prey, the Harpy Eagle, is under intense anthropogenic pressure due to historical and recent reductions in forest cover. We studied prey availability and use by Harpy Eagle on six breeding territories on the low- and mid-Xingu River, between 2013 and 2015. We evaluated food resource availability using the environmental-surveys database from two methods: terrestrial surveys (RAPELD method) and fauna rescue/flushing before vegetation suppression for the Belo Monte Hydroelectric Complex construction. Harpy Eagle diet was identified by prey remains sampled around six nest trees. Eighteen species of mammals, birds and reptiles comprised the prey items. Most prey species were sloths, primates and porcupines, which have arboreal habits and are found in forested areas, but two species, hoatzin and iguana, are usually associated with riverine habitats. The proportion of prey from each species predated on the nest best studied was different from estimated availability (χ2 = 54.23; df = 16; p < 0.001), however there was a positive correlation (rs = 0.7; p < 0.01) between prey species consumed and abundance available, where the predation was more on species more abundant. Continuous monitoring of the Harpy Eagle diet at these nests could evidence changes in the assemblage of prey species available for Harpy Eagles, due to changes in the seasonal flood pulse of the Xingu River to be caused by the operation of the hydroelectric dam, and changes in habitat features by forest reduction around breeding territories. We believe that it is important to consider the protection of remnants of forested areas in the landscape matrix surrounding the breeding territories to maintain the food resource availability and allow all pairs to successfully reproduce.