The phylogeny and ontogeny of autonomic control of the heart and cardiorespiratory interactions in vertebrates

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Botanical extracts: alternative control for silverleaf whitefly management in tomato

Bemisia tabaci (Hemiptera: Aleyrodidae) biotype B is one of the most limiting pests of tomato crops in the world. Tomato yield is currently dependent on the use of pesticides, which are problematic to farmers, consumers and the environment. A promising alternative to reduce the harmful effects caused by the indiscriminated use of synthetic insecticides is the use of insecticides of botanical origin. This study aimed to evaluate the effect of 3% (w/v) aqueous extracts from different structures of thirteen botanical species on the behavior of B. tabaci biotype B adults, as well as insecticidal activity of such aqueous extracts on B. tabaci eggs, nymphs, and adults infesting tomato plants. A distilled water solution was used as a negative control, and thiamethoxam insecticide (18 g/100 L of water) as a positive control. Leaf extract of Toona ciliata was observed to have the most efficient inhibitory effect in tests of extracts on whitefly behavior. Furthermore, the use of leaf extract of Toona ciliata led to the most drastic reduction in the number of adults and eggs on tomato leaflets. Leaf extract of Piper aduncum led to the greatest observed ovicidal effect (78.00% of non-hatched nymphs); however it was not effective against nymphs and adults. The leaf extracts of Trichilia pallida, Trichilia casaretti, and Toona ciliata showed the highest control indexes (67.9, 60.3, and 55.1%, respectively). For adults mortality, T. pallida was the most effective (72.8%). Our results indicate that application of extracts of T. pallida, T. ciliata, and T. casaretti are promising strategies to manage B. tabaci biotype B on tomato.

Galectin-1 exerts inhibitory effects during DENV-1 infection

Dengue virus (DENV) is an enveloped RNA virus that is mosquito-transmitted and can infect a variety of immune and non-immune cells. Response to infection ranges from asymptomatic disease to a severe disorder known as dengue hemorrhagic fever. Despite efforts to control the disease, there are no effective treatments or vaccines. In our search for new antiviral compounds to combat infection by dengue virus type 1 (DENV-1), we investigated the role of galectin-1, a widely-expressed mammalian lectin with functions in cell-pathogen interactions and immunoregulatory properties. We found that DENV-1 infection of cells in vitro exhibited caused decreased expression of Gal-1 in several different human cell lines, suggesting that loss of Gal-1 is associated with virus production. In test of this hypothesis we found that exogenous addition of human recombinant Gal-1 (hrGal-1) inhibits the virus production in the three different cell types. This inhibitory effect was dependent on hrGal-1 dimerization and required its carbohydrate recognition domain. Importantly, the inhibition was specific for hrGal-1, since no effect was observed using recombinant human galectin-3. Interestingly, we found that hrGal-1 directly binds to dengue virus and acts, at least in part, during the early stages of DENV-1 infection, by inhibiting viral adsorption and its internalization to target cells. To test the in vivo role of Gal-1 in DENV infection, Gal-1-deficient-mice were used to demonstrate that the expression of endogenous Galectin-1 contributes to resistance of macrophages to in vitro-infection with DENV-1 and it is also important to physiological susceptibility of mice to in vivo infection with DENV-1. These results provide novel insights into the functions of Gal-1 in resistance to DENV infection and suggest that Gal-1 should be explored as a potential antiviral compound.

Galectin-1 exerts inhibitory effects during DENV-1 infection

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Interaction between the septal area and the subfornical organ in the control of water intake induced by thirst-eliciting procedures

Rats bearing lesions in the septal area followed by lesions in the subfornical organ were submitted to various thirst-eliciting procedures. The rats with hyperdipsia induced by lesions of the septal area drank more water than either during the control period or after lesion of the subfornical organ under the same thirst-eliciting or angiotensin-liberating stimuli (polyethyleneglycol, isoproterenol, water deprivation and ligation of the inferior vena cava). The overdrinking elicited by lesions in the septal area was blocked after lesion of the subfornical organ. Neither hypovolemia, nor hypotension or water deprivation could elicit increased water intake in animals whose subfornical organ had been destroyed. Animals with lesions in the subfornical organ showed decreased water intake after cellular dehydration. The results obtained suggest that the subfornical organ acts as a more important structure than the septal area in the regulation of water intake elicited by angiotensin, with two opposite effects: a direct one facilitating water intake, and an indirect one inhibiting the septal area. The septal area has an inhibitory effect on the subfornical organ and on water intake. © 1980.

Role of alfa2-adrenoceptors in the lateral parabrachial nucleus in the control of body fluid homeostasis

Central α2-adrenoceptors and the pontine lateral parabrachial nucleus (LPBN) are involved in the control of sodium and water intake. Bilateral injections of moxonidine (α2-adrenergic/imidazoline receptor agonist) or noradrenaline into the LPBN strongly increases 0.3 M NaCl intake induced by a combined treatment of furosemide plus captopril. Injection of moxonidine into the LPBN also increases hypertonic NaCl and water intake and reduces oxytocin secretion, urinary sodium, and water excreted by cell-dehydrated rats, causing a positive sodium and water balance, which suggests that moxonidine injected into the LPBN deactivates mechanisms that restrain body fluid volume expansion. Pretreatment with specific α2-adrenoceptor antagonists injected into the LPBN abolishes the behavioral and renal effects of moxonidine or noradrenaline injected into the same area, suggesting that these effects depend on activation of LPBN α2-adrenoceptors. In fluid-depleted rats, the palatability of sodium is reduced by ingestion of hypertonic NaCl, limiting intake. However, in rats treated with moxonidine injected into the LPBN, the NaCl palatability remains high, even after ingestion of significant amounts of 0.3 M NaCl. The changes in behavioral and renal responses produced by activation of α2-adrenoceptors in the LPBN are probably a consequence of reduction of oxytocin secretion and blockade of inhibitory signals that affect sodium palatability. In this review, a model is proposed to show how activation of α2-adrenoceptors in the LPBN may affect palatability and, consequently, ingestion of sodium as well as renal sodium excretion.

Structural insights regarding an insecticidal Talisia esculenta protein and its biotechnological potential for Diatraea saccharalis larval control

Talisin is a seed-storage protein from Talisia esculenta that presents lectin-like activities, as well as proteinase-inhibitor properties. The present study aims to provide new in vitro and in silico biochemical information about this protein, shedding some light on its mechanistic inhibitory strategies. A theoretical three-dimensional structure of Talisin bound to trypsin was constructed in order to determine the relative interaction mode. Since the structure of non-competitive inhibition has not been elucidated, Talisin-trypsin docking was carried out using Hex v5.1, since the structure of non-competitive inhibition has not been elucidated. The predicted non-coincidence of the trypsin binding site is completely different from that previously proposed for Kunitz-type inhibitors, which demonstrate a substitution of an Arg(64) for the Glu(64) residue. Data, therefore, provide more information regarding the mechanisms of non-competitive plant proteinase inhibitors. Bioassays with Talisin also presented a strong insecticide effect on the larval development of Diatraea saccharalis, demonstrating LD50 and ED50 of ca. 2.0% and 1.5%, respectively. (C) 2011 Elsevier Inc. All rights reserved.

Chronic intermittent hypoxia alters glutamatergic control of sympathetic and respiratory activities in the commissural NTS of rats

Costa-Silva JH, Zoccal DB, Machado BH. Chronic intermittent hypoxia alters glutamatergic control of sympathetic and respiratory activities in the commissural NTS of rats. Am J Physiol Regul Integr Comp Physiol 302: R785-R793, 2012. First published December 28, 2011; doi:10.1152/ajpregu.00363.2011.-Sympathetic overactivity and altered respiratory control are commonly observed after chronic intermittent hypoxia (CIH) exposure. However, the central mechanisms underlying such neurovegetative dysfunctions remain unclear. Herein, we hypothesized that CIH (6% O-2 every 9 min, 8 h/day, 10 days) in juvenile rats alters glutamatergic transmission in the commissural nucleus tractus solitarius (cNTS), a pivotal site for integration of peripheral chemoreceptor inputs. Using an in situ working heart-brain stem preparation, we found that L-glutamate microinjections (1, 3, and 10 mM) into the cNTS of control rats (n = 8) evoked increases in thoracic sympathetic nerve (tSN) and central vagus nerve (cVN) activities combined with inhibition of phrenic nerve (PN) activity. Besides, the ionotropic glutamatergic receptor antagonism with kynurenic acid (KYN; 250 mM) in the cNTS of control group (n = 7) increased PN burst duration and frequency. In the CIH group (n = 10), the magnitude of L-glutamate-induced cVN excitation was smaller, and the PN inhibitory response was blunted (P < 0.05). In addition, KYN microinjections into the cNTS of CIH rats (n = 9) did not alter PN burst duration and produced smaller increases in its frequency compared with controls. Moreover, KYN microinjections into the cNTS attenuated the sympathoexcitatory response to peripheral chemoreflex activation in control but not in CIH rats (P < 0.05). These functional CIH-induced alterations were accompanied by a significant 10% increase of N-methyl-D-aspartate receptor 1 (NMDAR1) and glutamate receptor 2/3 (GluR2/3) receptor subunit density in the cNTS (n = 3-8, P < 0.05), evaluated by Western blot analysis. These data indicate that glutamatergic transmission is altered in the cNTS of CIH rats and may contribute to the sympathetic and respiratory changes observed in this experimental model.

INHIBITION OF OVIPOSITION BY NEEM EXTRACT: A BEHAVIORAL PERSPECTIVE FOR THE CONTROL OF THE MEDITERRANEAN FRUIT FLY (DIPTERA: TEPHRITIDAE)

The behavioral inhibitory effect of methanol extracts from neem leaves (Azadirachta indica A. Juss) at different concentrations (0, 10,000, 18,000, 32,000 and 56,000 ppm) was evaluated using naive and experienced medflies (Ceratitis capitata (Wied.)) ovipositing on the fruits of grape cv. 'Italia'. The grapes were immersed in the specific treatments and were exposed for 24 h to 3 pairs of female and male medflies, both nave and experienced, in a choice test. At concentrations >= 18,000 ppm, the extract that was applied to the grapes inhibited oviposition. The previous experience with treated grapes did not affect the response of the medflies. This study is the first step toward the application of the behavior control of the medflies as a tool in grape vineyards. The potential for using oviposition inhibitory in behavioral control of C. capitata are discussed.

Models of passive and active dendrite motoneuron pools and their differences in muscle force control

Motoneuron (MN) dendrites may be changed from a passive to an active state by increasing the levels of spinal cord neuromodulators, which activate persistent inward currents (PICs). These exert a powerful influence on MN behavior and modify the motor control both in normal and pathological conditions. Motoneuronal PICs are believed to induce nonlinear phenomena such as the genesis of extra torque and torque hysteresis in response to percutaneous electrical stimulation or tendon vibration in humans. An existing large-scale neuromuscular simulator was expanded to include MN models that have a capability to change their dynamic behaviors depending on the neuromodulation level. The simulation results indicated that the variability (standard deviation) of a maintained force depended on the level of neuromodulatory activity. A force with lower variability was obtained when the motoneuronal network was under a strong influence of PICs, suggesting a functional role in postural and precision tasks. In an additional set of simulations when PICs were active in the dendrites of the MN models, the results successfully reproduced experimental results reported from humans. Extra torque was evoked by the self-sustained discharge of spinal MNs, whereas differences in recruitment and de-recruitment levels of the MNs were the main reason behind torque and electromyogram (EMG) hysteresis. Finally, simulations were also used to study the influence of inhibitory inputs on a MN pool that was under the effect of PICs. The results showed that inhibition was of great importance in the production of a phasic force, requiring a reduced co-contraction of agonist and antagonist muscles. These results show the richness of functionally relevant behaviors that can arise from a MN pool under the action of PICs.

A possible new mechanism for the control of miRNA expression in neurons

The control of gene expression by miRNAs has been widely investigated in different species and cell types. Following a probabilistic rather than a deterministic regimen, the action of these short nucleotide sequences on specific genes depends on intracellular concentration,which in turn reflects the balance between biosynthesis and degradation. Recent studies have described the involvement of XRN2, an exoribonuclease, in miRNA degradation and PAPD4, an atypical poly(A) polymerase, in miRNA stability. Herein, we examined the expression of XRN2 and PAPD4 in developing and adult rat hippocampi. Combining bioinformatics and real-time PCR,we demonstrated that XRN2 and PAPD4 expression is regulated by the uncorrelated action of transcription factors, resulting in distinct gene expression profiles during development. Analyses of nuclei position and nestin labeling revealed that both proteins progressively accumulated during neuronal differentiation, and that they are weakly expressed in immature neurons and absent in glial and endothelial cells. Despite the differences in subcellular localization, both genes were concurrently identified within identical neuronal subpopulations, including specific inhibitory interneurons. Thus, we cope with a singular circumstance in biology: an almost complete intersected expression of functional-opposed genes, reinforcing that their antagonistically driven actions on miRNAs “make sense” if simultaneously present at the same cells. Considering that the transcriptome in the nervous system is finely tuned to physiological processes, it was remarkable that miRNA stability-related genes were oncurrently identified in neurons that play essential roles in cognitive functions such as memory and learning. In summary, this study reveals a possible new mechanism for the control of miRNA expression.

Biofilms on exposed monumental stones: mechanism of formation and development of new control methods

Within the stone monumental artefacts artistic fountains are extremely favorable to formation of biofilms, giving rise to biodegradation processes related with physical-chemical and visual aspect alterations, because of their particular exposure conditions. Microbial diversity of five fountains (two from Spain and three from Italy) was investigated. It was observed an ample similarity between the biodiversity of monumental stones reported in literature and that one found in studied fountains. Mechanical procedures and toxic chemical products are usually employed to remove such phototrophic patinas. Alternative methods based on natural antifouling substances are recently experimented in the marine sector, due to their very low environmental impact and for the bio settlement prevention on partially immersed structures of ships. In the present work groups of antibiofouling agents (ABAs) were selected from literature for their ability to interfere, at molecular level, with the microbial communication system “quorum sensing”, inhibiting the initial phase of biofilm formation. The efficacy of some natural antibiofoulants agents (ABAs) with terrestrial (Capsaicine - CS, Cinnamaldehyde - CI) and marine origin (Zosteric Acid - ZA, poly-Alkyl Pyridinium Salts – pAPS and Ceramium botryocarpum extract - CBE), incorporated into two commercial coatings (Silres BS OH 100 - S and Wacker Silres BS 290 - W) commonly used in stone conservation procedures were evaluated. The formation of phototrophic biofilms in laboratory conditions (on Carrara marble specimens and Sierra Elvira stone) and on two monumental fountains (Tacca’s Fountain 2 - Florence, Italy and Fountain from Patio de la Lindaraja - Alhambra Palace, Granada, Spain) has been investigated in the presence or absence of these natural antifouling agents. The natural antibiofouling agents, at tested concentrations, demonstrated a certain inhibitory effect. The silane-siloxane based silicone coating (W) mixing with ABAs was more suitable with respect to ethyl silicate coating (S) and proved efficacy against biofilm formation only when incompletely cured. The laboratory results indicated a positive action in inhibiting the patina formation, especially for poly-alkyl pyridinium salts, zosteric acid and cinnamaldehyde, while on site tests revealed a good effect for zosteric acid.

Improving adoptive T cell therapies of cancer by ectopic expression of miR181a to repress inhibitory phosphatases

Adoptive T cell therapy using antigen-specific T lymphocytes is a powerful immunotherapeutic approach against cancer. Nevertheless, many T cells against tumor-antigens exhibit only weak anti-tumoral response. To overcome this barrier it is necessary to improve the potency and anti-tumoral efficacy of these T cells. Activation and activity of T cells are tightly controlled to inhibit unwanted T cell responses and to reduce the risk of autoimmunity. Both are regulated by extrinsic signals and intrinsic mechanisms which suppress T cell activation. The intrinsic mechanisms include the expression of phosphatases that counteract the activation-inducing kinases. Modifying the expression of these phosphatases allows the targeted modulation of T cell reactivity. MicroRNAs (miRNAs) are regulatory small noncoding RNA molecules that control gene expression by targeting messenger RNAs in a sequence specific manner. Gene-specific silencing plays a key role in diverse biological processes, such as development, differentiation, and functionality. miR181a has been shown to be highly expressed in immature T cells that recognize low-affinity antigens.rnThe present study successfully shows that ectopic expression of miR181a is able to enhance the sensitivity of both murine and human T cells. In CD4+ T helper cells as well as in CD8+ cytotoxic T cells the overexpression of miR181a leads to downregulation of multiple phosphatases involved in the T cell receptor signaling pathway. Overexpression of miR181a in human T cells achieves a co-stimulatory independent activation and has an anti-apoptotic effect on CD4+ T helper cells. Additionally, increasing the amount of miR181a enhances the cytolytic activity of murine CD8+ TCRtg T cells in an antigen-specific manner.rnTo test miR181a overexpressing T cells in vivo, a mouse tumor model using a B cell lymphoma cell line (A20-HA) expressing the Influenza hemagglutinin (Infl.-HA) antigen was established. The expression of model antigens in tumor cell lines enables targeted elimination of tumors using TCRtg T cells. The transfer of miR181a overexpressing Infl.-HA TCRtg CD8+ T cells alone has no positive effect neither on tumor control nor on survival of A20-HA tumor-bearing mice. In contrast, the co-transfer of miR181a overexpressing Infl.-HA TCRtg CD8+ and CD4+ T cells leads to improved tumor control and prolongs survival of A20-HA tumor-bearing mice. This effect is characterized by higher amounts of effector T cells and the expansion of Infl.-HA TCRtg CD8+ T cells.rnAll effects were achieved by changes in expression of several genes including molecules involved in T cell differentiation, activation, and regulation, cytotoxic effector molecules, and receptors important for the homing process of T cells in miR181a overexpressing T cells. The present study demonstrates that miR181a is able to enhance the anti-tumoral response of antigen-specific T cells and is a promising candidate for improving adoptive cell therapy.

Do statins reduce the risk of aneurysm development? A case-control study

Recent studies in rats have demonstrated that statins may have an inhibitory effect on intracranial aneurysm (IA) development. The purpose of this study was to assess whether long-term statin use is associated with a reduced risk of IA formation in humans.

Inhibitory regulation of dendritic activity in vivo

The spatiotemporal control of neuronal excitability is fundamental to the inhibitory process. We now have a wealth of information about the active dendritic properties of cortical neurons including axonally generated sodium action potentials as well as local sodium spikelets generated in the dendrites, calcium plateau spikes, and NMDA spikes. All of these events have been shown to be highly modified by the spatiotemporal pattern of nearby inhibitory input which can drastically change the output firing mode of the neuron. This means that particular populations of interneurons embedded in the neocortical microcircuitry can more precisely control pyramidal cell output than has previously been thought. Furthermore, the output of any given neuron tends to feed back onto inhibitory circuits making the resultant network activity further dependent on inhibition. Network activity is therefore ultimately governed by the subcellular microcircuitry of the cortex and it is impossible to ignore the subcompartmentalization of inhibitory influence at the neuronal level in order to understand its effects at the network level. In this article, we summarize the inhibitory circuits that have been shown so far to act on specific dendritic compartments in vivo.