γ-Lactones from Persea americana and Persea fulva – in Vitro and in Silico Evaluation of Trypanosoma cruzi Activity

In the present study, five known γ-lactones (majoranolide B – 1 , majorenolide – 2 , majorynolide – 3 , lincomolide D – 4 , and isolinderanolide E – 5 ), as well as a new one (perseanolide – 6 ), were isolated from Persea fulva and P. americana. All isolated compounds exhibited potential activity against trypomastigote forms of Trypanosoma cruzi, whereas compounds 2 (EC₅₀ of 4.8 μM) and 6 (EC₅₀ of 3.6 μM) displayed superior activity than the positive control benznidazole (EC₅₀ of 16.4 μM), with selectivity index (SI) values of 17.8 and >55.6, respectively (benznidazole, SI>12.2). Molecular docking studies were performed for 1 – 6 against six T. cruzi molecular targets. Using this approach, we observed that, even though perseanolide ( 6 ) showed favorable docking to several studied targets, the results were especially promising for hypoxanthine phosphoribosyl transferase (PDB 1TC1). As PDB 1TC1 is associated to the transference of a monophosphorylated ribose from phosphoribosylpyrophosphate (PRPP) in the ribonucleotide synthesis pathway, this interaction may affect the survival of T. cruzi in mammalian cells. The data herein also indicate that possible intermolecular interactions between 6 and PDB 1TC1 derive from (i) hydrogen bonds in the α,β-unsaturated-γ-lactone unity and (ii) hydrophobic interactions in the long-chain alkyl group. Based on our results, perseanolide ( 6 ), reported for the first time in this work, can auspiciously contribute to future works regarding new trypanocidal agents.     

Vine mealybug sex pheromone increases citrus mealybug parasitism by Anagyrus sp. near pseudococci (Girault)

The present study was aimed at elucidating the role of lavandulyl senecioate (LS), the sex pheromone of Planococcus ficus, in host selection of the parasitoid Anagyrus sp. near pseudococci. Field trials were carried out in Portugal, Italy and Israel. The effect of LS on the parasitism rate of the wasp was determined by exposing sentinel mealybugs combined with pheromone dispensers impregnated with LS, in comparison with other baits: lavandulyl isovalerate (LI); planococcyl acetate (PAc); and unbaited control traps. In addition, in order to study the host location behavior of A. sp. near pseudococci, pheromone dispensers were placed at three different distances: inside the trap, 30 or 60 cm away from the trap. The number of parasitoid females inside the traps, the number of parasitized mealybugs, and the number of days required for the first parasitoid emergence were recorded. The response of A. sp. near pseudococci females to different doses of LS (25–1350 μg) was also evaluated using sticky plate traps. The rate of mealybug parasitism by A. sp. near pseudococci was significantly increased by LS in the three parasitoid populations. PAc and LI had no significant effect on the wasp parasitism rate in most of the trials. However, the Italian population of the parasitoid responded to PAc, showing apparently a different behavioral pattern. The number of parasitoid females trapped did not significantly differ between tested doses of LS. The use of LS as an arrestant in host location by the A. sp. near pseudococci female is discussed.     

Macrocytic Anemia and Mitochondriopathy Resulting from a Defect in Sideroflexin 4

We used exome sequencing to identify mutations in sideroflexin 4 (SFXN4) in two children with mitochondrial disease (the more severe case also presented with macrocytic anemia). SFXN4 is an uncharacterized mitochondrial protein that localizes to the mitochondrial inner membrane. sfxn4 knockdown in zebrafish recapitulated the mitochondrial respiratory defect observed in both individuals and the macrocytic anemia with megaloblastic features of the more severe case. In vitro and in vivo complementation studies with fibroblasts from the affected individuals and zebrafish demonstrated the requirement of SFXN4 for mitochondrial respiratory homeostasis and erythropoiesis. Our findings establish mutations in SFXN4 as a cause of mitochondriopathy and macrocytic anemia.     

Effects of trophic levels (chlorophyll and phosphorous content) in three different water bodies (urban lake,reservoir and aquaculture facility) on gill morphology of Nile tilapia (Oreochromis niloticus)

Histological and ultrastructural analyses of gills were observed in Nile tilapia collected from three different waterbodies in southeast Brazil: an urban lake in a park in the city of São Paulo, a reservoir in a rural city, and a commercial aquaculture facility. These waterbodies were analyzed and classified as hypereutrophic, eutrophic, and supereutrophic, respectively, with 310.00, 94.00, 28.00 of phosphate ( μg L^?1) and 65.49, 24.95, 12.83 of chlorophyll (μg L^?1). A significant difference in the histological alterations index (HAI) was observed only in fish from the urban lake, with the presence of cell hypertrophy, hyperplasia, aneurism, and other alterations. When compared to the other groups, a large quantity of rodlet cells was also observed in the urban group. These results demonstrate the correlation of eutrophic states of water with gill morphology. Also discussed is the premise that large amounts of organic material dissolved in water can alter the morphology of the fish gills.     

Mating Behavior and Performance in the Two Cosmopolitan Mealybug Species Planococcus citri and Pseudococcus calceolariae (Hemiptera: Pseudococcidae)

Mating strategies of mealybugs were investigated using two heterogeneric cosmopolitan species as case study: Planococcus citri (Risso) and Pseudococcus calceolariae (Maskell). Male mating behavior of the studied species differed in respect to mate selection, and frequency and duration of copulation. Females played an active role in mate selection, by either facilitating or resisting copulation. This is a first evidence of female sexual active behavior in scale insects. In both species, male predisposition to mate was affected by previous exposition to light. The frequency of courtship and copulation decreased with the age of females for Pl. citri but not for Ps. calceolariae. Mating frequency increased with female colony density in both species.     

Molecular characterization of different preproGnRHs in Astyanax altiparanae (Characiformes): Effects of GnRH on female reproduction

Gonadotropin‐releasing hormone (GnRH) is a key molecule in the initiation of the hypothalamic–pituitary–gonadal axis. Thus, knowledge about GnRH may contribute to the effectiveness of species reproduction. Using a Neotropical tetra Astyanax altiparanae as a fish model species, the GnRH forms were characterized at the molecular level and the role of injected GnRHs in vivo was evaluated. The full‐length complementary DNA (cDNA) sequences of preproGnRH2 (612 bp) and preproGnRH3 (407 bp) of A. altiparanae were obtained, and the GnRH1 form was not detected. The cDNA sequences of preproGnRH2 and preproGnRH3 were found to be conserved, but a change in the amino acid at position 8 of the GnRH3 decapeptide of A. altiparanae was observed. All the injected GnRHs stimulated lhβ messenger RNA (mRNA) expression but not fshβ mRNA expression, and only GnRH2 was able to increase maturation‐inducing steroid (MIS) levels and possibly stimulate oocyte release. Furthermore, only GnRH2 was able to start the entire reproductive hormonal cascade and induce spawning.     

Vesicular monoamine transporter 2 mediates fear behavior in mice

A subset of people exposed to a traumatic event develops post‐traumatic stress disorder (PTSD), which is associated with dysregulated fear behavior. Genetic variation in SLC18A2, the gene that encodes vesicular monoamine transporter 2 (VMAT2), has been reported to affect risk for the development of PTSD in humans. Here, we use transgenic mice that express either 5% (VMAT2‐LO mice) or 200% (VMAT2‐HI mice) of wild‐type levels of VMAT2 protein. We report that VMAT2‐LO mice have reduced VMAT2 protein in the hippocampus and amygdala, impaired monoaminergic vesicular storage capacity in both the striatum and frontal cortex, decreased monoamine metabolite abundance and a greatly reduced capacity to release dopamine upon stimulation. Furthermore, VMAT2‐LO mice showed exaggerated cued and contextual fear expression, altered fear habituation, inability to discriminate threat from safety cues, altered startle response compared with wild‐type mice and an anxiogenic‐like phenotype, but displayed no deficits in social function. By contrast, VMAT2‐HI mice exhibited increased VMAT2 protein throughout the brain, higher vesicular storage capacity and greater dopamine release upon stimulation compared with wild‐type controls. Behaviorally, VMAT2‐HI mice were similar to wild‐type mice in most assays, with some evidence of a reduced anxiety‐like responses. Together, these data show that presynaptic monoamine function mediates PTSD‐like outcomes in our mouse model, and suggest a causal link between reduced VMAT2 expression and fear behavior, consistent with the correlational relationship between VMAT2 genotype and PTSD risk in humans. Targeting this system is a potential strategy for the development of pharmacotherapies for disorders like PTSD.     

Induction of β-1,3-glucanase in seeds of maize defective-kernel mutant (827Kpro1)

β-1,3-glucanases are found in organisms as diverse as plants, animals, bacteria and fungi. In plants, such enzymes are not only associated with defense mechanisms against pathogens, but also play critical roles in physiological and developmental processes. Here we identified a new β-1,3-glucanase in maize seeds, and named it ZmGlucA. Sequence analysis revealed that ZmGlucA belongs to the class A of β-1,3-glucanase, a class related to defense and physiological processes in plants. mRNA and protein assays showed that zmGlucA is expressed exclusively in seeds, and it is differentially regulated during seed development. Additionally, zmGlucA expression is strongly induced in seeds of the mutant dek 827Kpro1, which is defective for embryo and endosperm development. Our data support the idea that ZmGlucA protein is relevant to seed development.     

Synaptic integration gradients in single cortical pyramidal cell dendrites

Cortical pyramidal neurons receive thousands of synaptic inputs arriving at different dendritic locations with varying degrees of temporal synchrony. It is not known if different locations along single cortical dendrites integrate excitatory inputs in different ways. Here we have used two-photon glutamate uncaging and compartmental modeling to reveal a gradient of nonlinear synaptic integration in basal and apical oblique dendrites of cortical pyramidal neurons. Excitatory inputs to the proximal dendrite sum linearly and require precise temporal coincidence for effective summation, whereas distal inputs are amplified with high gain and integrated over broader time windows. This allows distal inputs to overcome their electrotonic disadvantage, and become surprisingly more effective than proximal inputs at influencing action potential output. Thus, single dendritic branches can already exhibit nonuniform synaptic integration, with the computational strategy shifting from temporal coding to rate coding along the dendrite.