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1.
ACS Pharmacol Transl Sci ; 7(3): 834-854, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38481695

RESUMO

G protein-coupled receptors show preference for G protein subtypes but can recruit multiple G proteins with various downstream signaling cascades. This functional selection can guide drug design. Dopamine receptors are both stimulatory (D1-like) and inhibitory (D2-like) with diffuse expression across the central nervous system. Functional selectivity of G protein subunits may help with dopamine receptor targeting and their downstream effects. Three bioluminescence-based assays were used to characterize G protein coupling and function with the five dopamine receptors. Most proximal to ligand binding was the miniG protein assay with split luciferase technology used to measure recruitment. For endogenous and selective ligands, the G-CASE bioluminescence resonance energy transfer (BRET) assay measured G protein activation and receptor selectivity. Downstream, the BRET-based CAMYEN assay quantified cyclic adenosine monophosphate (cAMP) changes. Several dopamine receptor agonists and antagonists were characterized for their G protein recruitment and cAMP effects. G protein selectivity with dopamine revealed potential Gq coupling at all five receptors, as well as the ability to activate subtypes with the "opposite" effects to canonical signaling. D1-like receptor agonist (+)-SKF-81297 and D2-like receptor agonist pramipexole showed selectivity at all receptors toward Gs or Gi/o/z activation, respectively. The five dopamine receptors show a wide range of potentials for G protein coupling and activation, reflected in their downstream cAMP signaling. Targeting these interactions can be achieved through drug design. This opens the door to pharmacological treatment with more selectivity options for inducing the correct physiological events.

2.
Naunyn Schmiedebergs Arch Pharmacol ; 397(1): 617-626, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37490122

RESUMO

Clonidine has various clinical effects mediated by agonism of α1- or α2-adrenoceptors and the blocking of hyperpolarization-activated-nucleotide-gated pacemaker channels (HCN). It is unknown whether clonidine can also stimulate human cardiac histamine H2 receptors (hH2Rs). We used isolated electrically stimulated left and spontaneously beating right atrial preparations from mice overexpressing the hH2R specifically in the heart (H2-TG), and spontaneously beating right atrial preparations of guinea pigs for comparison. Moreover, we studied isolated electrically stimulated muscle strips from the human right atrium. Clonidine (1, 3, and 10 µM) increased force of contraction in isolated left atrial preparations from H2-TG mice. In contrast, clonidine reduced the spontaneous beating rate in right atrial preparations from H2-TG. Clonidine raised the beating rate in guinea pig right atrial preparations. Clonidine failed to increase the force of contraction but reduced beating rate in wild-type litter mate mice (WT). In WT, histamine failed to increase the force of contraction in left atrial preparations and beating rate in right atrial preparations. Clonidine (10 µM) increased the force of contraction in isolated human right atrial preparations. The positive inotropic effect in the human atrium was attenuated by cimetidine (10 µM). Clonidine increased the beating rate of the isolated spontaneously beating guinea pig right atrium and acted as a H2R partial agonist. Furthermore, clonidine showed binding to the guinea pig H2R (100 µM) using HEK cells in a recombinant expression system (pKi < 4.5) but hardly to the human H2R. These data suggest that clonidine can functionally activate cardiac human H2R.


Assuntos
Clonidina , Histamina , Humanos , Camundongos , Animais , Cobaias , Histamina/farmacologia , Clonidina/farmacologia , Átrios do Coração , Receptores Histamínicos H2/genética , Cimetidina , Contração Miocárdica , Receptores Histamínicos H1
3.
ACS Med Chem Lett ; 14(11): 1589-1595, 2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-37974943

RESUMO

Radioligands used previously for histamine H3 receptor (H3R) are accompanied by a number of disadvantages. In this study, we report the synthesis of the new H3R radioligand [3H]UR-MN259 ([3H]11) with high (radio)chemical purity and stability. The radioligand exhibits sub-nanomolar affinity for the target receptor (pKi (H3R) = 9.56) and displays an outstanding selectivity profile within the histamine receptor family (>100,000-fold selective). [3H]UR-MN259 is ideally suitable for the characterization of H3R ligands in competition binding and shows one-site binding to the H3R in saturation binding experiments. The radiotracer shows fast association to the receptor (τassoc = 6.11 min), as well as full dissociation from the receptor (τdissoc = 14.48 min) in kinetic binding studies. The distinguished profile of [3H]UR-MN259 makes it a highly promising pharmacological tool to further investigate the role of the H3R in the CNS.

4.
Teach Learn Med ; : 1-11, 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37266994

RESUMO

Phenomenon: In 2011, the American Medical Association added a section on professionalism and social media (i.e., e-professionalism) to the Code of Medical Ethics. Given the constantly evolving nature of social media use, research is needed to explore the attitudes and behaviors of current medical students, for most of whom social media has been a central facet of interpersonal communication and society since they were born. The goal of the current study is to examine students' social media use and attitudes related to online professionalism. Approach: Two-hundred-twenty-two medical students completed a mixed-methods cross-sectional online survey assessing perceptions of professionalism on social media. The survey was informed using the theory of planned behavior and included validated measures of attitudes, norms, and perceived behavioral control related to social media use and online professionalism. We analyzed data using thematic analysis and descriptive statistics and t-tests were conducted using SPSS 26. Qualitative and quantitative data were integrated during the data interpretation phase. Findings: Quantitative results revealed that students had a positive attitude toward having a social media presence as medical students and future physicians. Students reported: positive attitudes toward sharing positive thoughts, posting photos with family members, and posting photos in white coats or scrubs; neutral attitudes toward posting personal and political opinions; negative attitudes toward posting photos with alcohol, commenting about colleagues or the workplace, using profanity, connecting with patients, and commenting about patients. T-tests revealed significant differences between what students consider to be professional online behaviors for themselves as medical students versus what they believe society will expect of them as a physician. Students reported strong perceived behavioral control regarding professional social media behavior. While students reported they would face some difficulty "cleaning up" some previous content, students strongly disagreed that people's opinions of their online professional image were beyond their control. The qualitative analysis revealed students' perceptions of (a) what it means to demonstrate "online professionalism," (b) the challenges they face related to social media, and (c) training and standards related to social media use. Insights: Overall, our study confirms that students would benefit from e-professionalism training that is not merely disciplinary, but offers them evidence-based recommendations for maintaining medical professionalism while also embracing their personal identity and the benefits of social media as a (future) physician. Policies, guidelines, and training programs should constantly evolve as social norms regarding online communication and online identities evolve.

5.
Naunyn Schmiedebergs Arch Pharmacol ; 396(12): 3809-3822, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37354215

RESUMO

Ergometrine (6aR,9R)-N-((S)-1-hydroxypropan-2-yl)-7-methyl-4,6,6a,7,8,9-hexa-hydro-indolo-[4,3-fg]chinolin-9-carboxamide or lysergide acid ß-ethanolamide or ergonovine) activates several types of serotonin and histamine receptors in the animal heart. We thus examined whether ergometrine can activate human serotonin 5-HT4 receptors (h5-HT4R) and/or human histamine H2 receptors (hH2R) in the heart of transgenic mice and/or in the human isolated atrium. Force of contraction or beating rates were studied in electrically stimulated left atrial or spontaneously beating right atrial preparations or spontaneously beating isolated retrogradely perfused hearts (Langendorff setup) of mice with cardiac specific overexpression of the h5-HT4R (5-HT4-TG) or of mice with cardiac specific overexpression of the hH2R (H2-TG) or in electrically stimulated human right atrial preparations obtained during cardiac surgery. Western blots to assess phospholamban (PLB) phosphorylation on serine 16 were performed. Ergometrine exerted concentration- and time-dependent positive inotropic effects and positive chronotropic effects in atrial preparations starting at 0.3 µM and reaching a plateau at 10 µM in H2-TGs (n = 7). This was accompanied by an increase in PLB phosphorylation at serine 16. Ergometrine up 10 µM failed to increase force of contraction in left atrial preparations from 5-HT4-TGs (n = 5). Ten micrometer ergometrine increased the force of contraction in isolated retrogradely perfused spontaneously beating heart preparations (Langendorff setup) from H2-TG but not 5-HT4-TG. In the presence of the phosphodiesterase inhibitor cilostamide (1 µM), ergometrine at 10 µM exerted positive inotropic effects in isolated electrically stimulated human right atrial preparations, obtained during cardiac surgery, and these effects were eliminated by 10 µM of the H2R antagonist cimetidine but not by 10 µM of the 5-HT4R antagonist tropisetron. Furthermore, ergometrine showed binding to human histamine H2 receptors (at 100 µM and 1 mM) using HEK cells in a recombinant expression system (pKi < 4.5, n = 3). In conclusion, we suggest that ergometrine is an agonist at cardiac human H2Rs.


Assuntos
Fibrilação Atrial , Serotonina , Humanos , Camundongos , Animais , Serotonina/farmacologia , Histamina , Contração Miocárdica , Átrios do Coração , Camundongos Transgênicos , Serina/farmacologia , Receptores Histamínicos H2
6.
Sci Rep ; 12(1): 9637, 2022 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-35688965

RESUMO

The signalling of the D2 receptor (D2R), a G protein-coupled receptor (GPCR), is a complex process consisting of various components. For the screening of D2R ligands, methods quantifying distinct second messengers such as cAMP or the interaction of the receptor with ß-arrestin, are commonly employed. In contrast, a label-free biosensor technology like dynamic mass redistribution (DMR), where it is mostly unknown how the individual signalling pathways contribute to the DMR signal, provides a holistic readout of the complex cellular response. In this study, we report the successful application of the DMR technology to CHO-K1 cells stably expressing the human dopamine D2long receptor. In real-time kinetic experiments, studies of D2R reference compounds yielded results for agonists and antagonists that were consistent with those obtained by conventional methods and also allowed a discrimination between partial and full agonists. Furthermore, investigations on the signalling pathway in CHO-K1 hD2longR cells identified the Gαi/o protein as the main proximal trigger of the observed DMR response. The present study has shown that the DMR technology is a valuable method for the characterisation of putative new ligands and, due to its label-free nature, suggests its use for deorphanisation studies of GPCRs.


Assuntos
Receptores Acoplados a Proteínas G , Transdução de Sinais , Animais , Cricetinae , Cricetulus , Proteínas de Ligação ao GTP/metabolismo , Humanos , Ligantes , Receptores Acoplados a Proteínas G/metabolismo , beta-Arrestinas/metabolismo
7.
J Med Chem ; 64(12): 8684-8709, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34110814

RESUMO

3-(2-Amino-4-methylthiazol-5-yl)propyl-substituted carbamoylguanidines are potent, subtype-selective histamine H2 receptor (H2R) agonists, but their applicability as pharmacological tools to elucidate the largely unknown H2R functions in the central nervous system (CNS) is compromised by their concomitant high affinity toward dopamine D2-like receptors (especially to the D3R). To improve the selectivity, a series of novel carbamoylguanidine-type ligands containing various heterocycles, spacers, and side residues were rationally designed, synthesized, and tested in binding and/or functional assays at H1-4 and D2long/3 receptors. This study revealed a couple of selective candidates (among others 31 and 47), and the most promising ones were screened at several off-target receptors, showing good selectivities. Docking studies suggest that the amino acid residues (3.28, 3.32, E2.49, E2.51, 5.42, and 7.35) are responsible for the different affinities at the H2- and D2long/3-receptors. These results provide a solid base for the exploration of the H2R functions in the brain in further studies.


Assuntos
Guanidinas/farmacologia , Agonistas dos Receptores Histamínicos/farmacologia , Receptores Histamínicos H2/metabolismo , Tiazóis/farmacologia , Animais , Sítios de Ligação , Guanidinas/síntese química , Guanidinas/metabolismo , Cobaias , Células HEK293 , Agonistas dos Receptores Histamínicos/síntese química , Agonistas dos Receptores Histamínicos/metabolismo , Humanos , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Ratos , Receptores de Dopamina D2/química , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D3/química , Receptores de Dopamina D3/metabolismo , Receptores Histamínicos H2/química , Células Sf9 , Relação Estrutura-Atividade , Tiazóis/síntese química , Tiazóis/metabolismo
8.
Eur J Med Chem ; 214: 113190, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33548637

RESUMO

Even today, the role of the histamine H2 receptor (H2R) in the central nervous system (CNS) is widely unknown. In previous research, many dimeric, high-affinity and subtype-selective carbamoylguanidine-type ligands such as UR-NK22 (5, pKi = 8.07) were reported as H2R agonists. However, their applicability to the study of the H2R in the CNS is compromised by their molecular and pharmacokinetic properties, such as high molecular weight and, consequently, a limited bioavailability. To address the need for more drug-like H2R agonists with high affinity, we synthesized a series of monomeric (thio)carbamoylguanidine-type ligands containing various spacers and side-chain moieties. This structural simplification resulted in potent (partial) agonists (guinea pig right atrium, [35S]GTPγS and ß-arrestin2 recruitment assays) with human (h) H2R affinities in the one-digit nanomolar range (pKi (139, UR-KAT523): 8.35; pKi (157, UR-MB-69): 8.69). Most of the compounds presented here exhibited an excellent selectivity profile towards the hH2R, e.g. 157 being at least 3800-fold selective within the histamine receptor family. The structural similarities of our monomeric ligands to pramipexole (6), a dopamine receptor agonist, suggested an investigation of the binding behavior at those receptors. The target compounds were (partial) agonists with moderate affinity at the hD2longR and agonists with high affinity at the hD3R (e.g. pKi (139, UR-KAT523): 7.80; pKi (157, UR-MB-69): 8.06). In summary, we developed a series of novel, more drug-like H2R and D3R agonists for the application in recombinant systems in which either the H2R or the D3R is solely expressed. Furthermore, our ligands are promising lead compounds in the development of selective H2R agonists for future in vivo studies or experiments utilizing primary tissue to unravel the role and function of the H2R in the CNS.


Assuntos
Agonistas de Dopamina/farmacologia , Guanidinas/farmacologia , Receptores de Dopamina D3/agonistas , Receptores Histamínicos H2/metabolismo , Animais , Células Cultivadas , Agonistas de Dopamina/síntese química , Agonistas de Dopamina/química , Relação Dose-Resposta a Droga , Guanidinas/síntese química , Guanidinas/química , Cobaias , Células HEK293 , Humanos , Ligantes , Estrutura Molecular , Relação Estrutura-Atividade
9.
J Osteopath Med ; 121(3): 247-253, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33635961

RESUMO

Context: Research has been scarce on health professionals' knowledge about guidelines regulating service dogs in a clinical setting. Gaining insight into health professionals' understanding of Americans with Disabilities Act (ADA) regulations concerning service dogs is critical for navigating compliance and reducing risk. Misinformation about service dogs could influence decisions affecting policy and care, leading to poor treatment and suboptimal health outcomes for patients with service animals. Objectives: To assess health professionals' knowledge about ADA regulations and beliefs about workplace protocols and training related to service dogs. Methods: The study used snowball sampling to distribute surveys to health professionals from around the United States. Initial outreach occurred using mailing lists, investigators' personal networks, and social media. The survey contained 24 items. True and false questions were used to test ADA knowledge and then coded as correct or incorrect. Most closed-end questions were measured on a 5-point Likert scale using frequencies and descriptive statistics. A one-way analysis of variance (ANOVA) was conducted to test whether variables, such as encounters to service dogs, affected knowledge of ADA requirements. Results: The survey was completed by 441 health professionals from around the country. Most (234; 53.1%) worked in a hospital and came from a range of professional backgrounds (nurses, 155 [35.2%]; physicians, 71 [16.1%]). While nearly three-quarters (318 [73.1%]) of participants said their workplace had a policy on service animals, 113 (34.9%) of those said they were unfamiliar with the policy and 236 (54.5%) said they had not received adequate training on the topic. Most participants did not know basic ADA policy requirements related to service dogs. Only those who were extremely familiar with policy (F=4.613; p=0.001) and those who strongly agreed that they knew the differences between service dogs and other classes of animals (F=5.906; p=0.000) scored higher on the knowledge test than those who disagreed. Conclusions: Our results suggest that increased familiarity and training leads to higher knowledge about service dogs and ADA policy. Health professionals need additional education on ADA service dog regulations and hospital policy in order to minimize risk and ensure patients with service dogs receive optimal care.


Assuntos
Pessoas com Deficiência , Médicos , Animais de Trabalho , Animais , Cães , Pessoal de Saúde , Humanos , Estados Unidos , Local de Trabalho
10.
J Neurosci ; 41(9): 1970-1981, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33452222

RESUMO

Attending to a stimulus enhances the neuronal responses to it, while responses to nonattended stimuli are not enhanced and may even be suppressed. Although the neural mechanisms of response enhancement for attended stimuli have been intensely studied, the neural mechanisms underlying attentional suppression remain largely unknown. It is uncertain whether attention acts to suppress the processing in sensory cortical areas that would otherwise process the nonattended stimulus or the subcortical input to these cortical areas. Moreover, the neurochemical mechanisms inducing a reduction or suppression of neuronal responses to nonattended stimuli are as yet unknown. Here, we investigated how attention directed toward visual processing cross-modally acts to suppress vestibular responses in the human brain. By using functional magnetic resonance spectroscopy in a group of female and male subjects, we find that attention to visual motion downregulates in a load-dependent manner the concentration of excitatory neurotransmitter (glutamate and its precursor glutamine, referred to together as Glx) within the parietoinsular vestibular cortex (PIVC), a core cortical area of the vestibular system, while leaving the concentration of inhibitory neurotransmitter (GABA) in PIVC unchanged. This makes PIVC less responsive to excitatory thalamic vestibular input, as corroborated by functional magnetic resonance imaging. Together, our results suggest that attention acts to suppress the processing of nonattended sensory cues cortically by neurochemically rendering the core cortical area of the nonattended sensory modality less responsive to excitatory thalamic input.SIGNIFICANCE STATEMENT Here, we address a fundamental problem that has eluded attention research for decades, namely, how the brain ignores irrelevant stimuli. To date, three classes of solutions to this problem have been proposed: (1) enhancement of GABAergic interneuron activity in cortex, (2) downregulation of glutamatergic cell activity in cortex; and (3) downregulation of neural activity in thalamic projection areas, which would then provide the cortex with less input. Here, we use magnetic resonance spectroscopy in humans and find support for the second hypothesis, implying that attention to one sensory modality involves the suppression of irrelevant stimuli of another sensory modality by downregulating glutamate in the cortex.


Assuntos
Atenção/fisiologia , Córtex Cerebral/fisiologia , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Adulto , Feminino , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Estimulação Luminosa , Percepção Visual/fisiologia , Adulto Jovem
11.
J Prim Care Community Health ; 11: 2150132720963686, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33048001

RESUMO

Health degree programs provide opportunities to reduce disparities in care for LGBTQ patients by exposing students to LGBTQ communities and current health issues. However, LGBTQ content is mostly absent from medical school curricula. This mixed method assessment study, conducted during the 2018 to 2019 academic year, examined the feasibility of implementing a medical student journal club focused specifically on LGBTQ health issues as a complementary training tool to support efforts to create an inclusive educational environment. Compared to the pre-test, mean response scores increased for most of the parameters including familiarity with LGBTQ healthcare issues, confidence in the ability to identify harmful medical provider practices, and reading and assessing scientific literature. Qualitative data showed increased confidence, comfort and knowledge about LGBTQ health barriers. This study offers a framework for using a journal club to provide an effective platform for enhancing students' LGBTQ cultural humility and research literacy.


Assuntos
Minorias Sexuais e de Gênero , Estudantes de Medicina , Currículo , Atenção à Saúde , Humanos
12.
Int J Mol Sci ; 21(17)2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32847148

RESUMO

Investigations on functional selectivity of GPCR ligands have become increasingly important to identify compounds with a potentially more beneficial side effect profile. In order to discriminate between individual signaling pathways, the determination of ß-arrestin2 recruitment, in addition to G-protein activation, is of great value. In this study, we established a sensitive split luciferase-based assay with the ability to quantify ß-arrestin2 recruitment to D2long and D3 receptors and measure time-resolved ß-arrestin2 recruitment to the D2long receptor after agonist stimulation. We were able to characterize several standard (inverse) agonists as well as antagonists at the D2longR and D3R subtypes, whereas for the D4.4R, no ß-arrestin2 recruitment was detected, confirming previous reports. Extensive radioligand binding studies and comparisons with the respective wild-type receptors confirm that the attachment of the Emerald luciferase fragment to the receptors does not affect the integrity of the receptor proteins. Studies on the involvement of GRK2/3 and PKC on the ß-arrestin recruitment to the D2longR and D3R, as well as at the D1R using different kinase inhibitors, showed that the assay could also contribute to the elucidation of signaling mechanisms. Its broad applicability, which provides concentration-dependent and kinetic information on receptor/ß-arrestin2 interactions, renders this homogeneous assay a valuable method for the identification of biased agonists.


Assuntos
Bioensaio/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Luciferases/metabolismo , Receptores de Dopamina D2/metabolismo , beta-Arrestina 2/metabolismo , Animais , Células HEK293 , Humanos , Cinética , Ligantes , Luciferases/análise , Luciferases/genética , Ligação Proteica , Receptores de Dopamina D2/agonistas , Receptores de Dopamina D2/análise , beta-Arrestina 2/agonistas , beta-Arrestina 2/análise
13.
J Neurosci ; 40(5): 1110-1119, 2020 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-31818978

RESUMO

Previous studies in human subjects reported that the parieto-insular vestibular cortex (PIVC), a core area of the vestibular cortex, is inhibited when visual processing is prioritized. However, it has remained unclear which networks in the brain modulate this inhibition of PIVC. Based on previous results showing that the inhibition of PIVC is strongly influenced by visual attention, we here examined whether attention networks in the parietooccipital cortex modulate the inhibition of PIVC. Using diffusion-weighted and resting-state fMRI in a group of female and male subjects, we found structural and functional connections between PIVC and the posterior parietal cortex (PPC), a major brain region of the cortical attention network. We then temporarily inhibited PPC by repetitive transcranial magnetic stimulation (rTMS) and hypothesized that the modulatory influence of PPC over PIVC would be reduced; and, as a result, PIVC would be less inhibited. Subjects performed a visual attentional tracking task immediately after rTMS, and the inhibition of PIVC during attentive tracking was measured with fMRI. The results showed that the inhibition of PIVC during attentive tracking was less pronounced compared with sham rTMS. We also examined the effects of inhibitory rTMS over the occipital cortex and found that the visual-vestibular posterior insular cortex area was less activated during attentive tracking compared with sham rTMS or rTMS over PPC. Together, these results suggest that attention networks in the parietooccipital cortex modulate activity in core areas of the vestibular cortex during attentive visual processing.SIGNIFICANCE STATEMENT Although multisensory integration is generally considered beneficial, it can become detrimental when cues from different senses are in conflict. The occurrence of such multisensory conflicts can be minimized by inhibiting core cortical areas of the subordinate sensory system (e.g., vestibular), thus reducing potential conflict with ongoing processing of the prevailing sensory (e.g., visual) cues. However, it has remained unclear which networks in the brain modulate the magnitude of inhibition of the subordinate sensory system. Here, by investigating the inhibition of the vestibular sensory system when visual processing is prioritized, we show that attention networks in the parietooccipital cortex modulate the magnitude of inhibition of the vestibular cortex.


Assuntos
Atenção/fisiologia , Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Percepção Visual/fisiologia , Adulto , Mapeamento Encefálico , Córtex Cerebral/anatomia & histologia , Córtex Cerebral/fisiologia , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Masculino , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Lobo Occipital/anatomia & histologia , Lobo Occipital/fisiologia , Lobo Parietal/anatomia & histologia , Lobo Parietal/fisiologia , Estimulação Magnética Transcraniana , Adulto Jovem
14.
J Evol Biol ; 31(8): 1165-1179, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29845691

RESUMO

Anthropogenic interference forces species to respond to changing environmental conditions. One possible response is dispersal and concomitant range shifts, allowing individuals to escape unfavourable conditions or to track the shifting climate niche. Range expansions depend on both dispersal capacity and the ability to establish populations beyond the former range. We here compare well-established core populations with recently established edge populations in the currently northward expanding butterfly Lycaena tityrus. Edge populations were characterized by shorter development times and smaller size, a higher sensitivity to high temperature and an enhanced exploratory behaviour. The differences between core and edge populations found suggest adaptation to local climates and an enhanced dispersal ability in edge populations. In particular, enhanced exploratory behaviour may be advantageous in all steps of the dispersal process and may have facilitated the current range expansion. This study describes differences associated with a current range expansion, knowledge which might be useful for a better understanding of species responses to environmental change. We further report on variation between males and females in morphology and flight behaviour, with males showing a longer flight endurance and more pronounced exploratory behaviour than females.


Assuntos
Distribuição Animal/fisiologia , Borboletas/genética , Borboletas/fisiologia , Voo Animal/fisiologia , Animais , Comportamento Animal , Evolução Biológica , Borboletas/crescimento & desenvolvimento , Feminino , Larva/genética , Larva/crescimento & desenvolvimento , Larva/fisiologia , Masculino , Modelos Biológicos , Pupa/genética , Pupa/crescimento & desenvolvimento , Pupa/fisiologia
15.
J Neurosci ; 36(50): 12720-12728, 2016 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-27821579

RESUMO

The midposterior fundus of the Sylvian fissure in the human brain is central to the cortical processing of vestibular cues. At least two vestibular areas are located at this site: the parietoinsular vestibular cortex (PIVC) and the posterior insular cortex (PIC). It is now well established that activity in sensory systems is subject to cross-modal attention effects. Attending to a stimulus in one sensory modality enhances activity in the corresponding cortical sensory system, but simultaneously suppresses activity in other sensory systems. Here, we wanted to probe whether such cross-modal attention effects also target the vestibular system. To this end, we used a visual multiple-object tracking task. By parametrically varying the number of tracked targets, we could measure the effect of attentional load on the PIVC and the PIC while holding the perceptual load constant. Participants performed the tracking task during functional magnetic resonance imaging. Results show that, compared with passive viewing of object motion, activity during object tracking was suppressed in the PIVC and enhanced in the PIC. Greater attentional load, induced by increasing the number of tracked targets, was associated with a corresponding increase in the suppression of activity in the PIVC. Activity in the anterior part of the PIC decreased with increasing load, whereas load effects were absent in the posterior PIC. Results of a control experiment show that attention-induced suppression in the PIVC is stronger than any suppression evoked by the visual stimulus per se. Overall, our results suggest that attention has a cross-modal modulatory effect on the vestibular cortex during visual object tracking. SIGNIFICANCE STATEMENT: In this study we investigate cross-modal attention effects in the human vestibular cortex. We applied the visual multiple-object tracking task because it is known to evoke attentional load effects on neural activity in visual motion-processing and attention-processing areas. Here we demonstrate a load-dependent effect of attention on the activation in the vestibular cortex, despite constant visual motion stimulation. We find that activity in the parietoinsular vestibular cortex is more strongly suppressed the greater the attentional load on the visual tracking task. These findings suggest cross-modal attentional modulation in the vestibular cortex.


Assuntos
Atenção/fisiologia , Córtex Cerebral/fisiologia , Percepção de Movimento/fisiologia , Desempenho Psicomotor/fisiologia , Adulto , Mapeamento Encefálico , Cognição/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/fisiologia , Lobo Parietal/fisiologia , Vestíbulo do Labirinto/fisiologia , Campos Visuais/fisiologia , Adulto Jovem
16.
PLoS One ; 9(10): e109236, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25347318

RESUMO

BACKGROUND: The Asian Citrus Psyllid (ACP), Diaphorina citri, can transmit the bacterium Candidatus Liberibacter while feeding on citrus flush shoots. This bacterium causes Huanglongbing (HLB), a major disease of citrus cultivation worldwide necessitating the development of new tools for ACP surveillance and control. The olfactory system of ACP is sensitive to variety of odorants released by citrus plants and offers an opportunity to develop new attractants and repellents. RESULTS: In this study, we performed single-unit electrophysiology to identify odorants that are strong activators, inhibitors, and prolonged activators of ACP odorant receptor neurons (ORNs). We identified a suite of odorants that activated the ORNs with high specificity and sensitivity, which may be useful in eliciting behavior such as attraction. In separate experiments, we also identified odorants that evoked prolonged ORN responses and antagonistic odorants able to suppress neuronal responses to activators, both of which can be useful in lowering attraction to hosts. In field trials, we tested the electrophysiologically identified activating odorants and identified a 3-odor blend that enhances trap catches by ∼230%. CONCLUSION: These findings provide a set of odorants that can be used to develop affordable and safe odor-based surveillance and masking strategies for this dangerous pest insect.


Assuntos
Monitoramento Ambiental , Hemípteros , Controle de Insetos , Odorantes , Animais , Neurônios Receptores Olfatórios/efeitos dos fármacos , Neurônios Receptores Olfatórios/fisiologia
17.
Chem Senses ; 39(6): 539-49, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24904081

RESUMO

Olfactory systems discriminate odorants very efficiently and herbivorous insects use them to find hosts in confounding and complex odor landscapes. The Asian citrus psyllid (ACP), Diaphorina citri, feeds on citrus flush and transmits Candidatus Liberibacter that causes citrus greening disease globally. Here, we perform a systematic analysis of odor detection in the ACP antenna using single-unit electrophysiology of rhinarial plate sensilla to a large panel of odorants from plants. We identify neurons that respond strongly to odorants found in the host citrus plants. Comparisons with the generalist yeast-feeding Drosophila melanogaster and specialist anthropophilic Anopheles gambiae reveal differences in odor-coding strategies for the citrus-seeking ACP. These findings provide a foundation for understanding host-odor coding in herbivorous insects.


Assuntos
Citrus/microbiologia , Hemípteros/microbiologia , Hemípteros/fisiologia , Herbivoria , Doenças das Plantas/microbiologia , Animais , Antenas de Artrópodes/fisiologia , Citrus/fisiologia , Drosophila melanogaster/fisiologia , Masculino , Odorantes/análise , Olfato
18.
J Econ Entomol ; 97(6): 1861-7, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15666737

RESUMO

A process for removing or killing California red scale, Aonidiella aurantii (Maskell), from citrus fruit as a postharvest treatment was evaluated. The process subjects the fruit to vacuum, steam, and vacuum that physically removes red scale from the fruit and kills those scales that are not removed from the fruit. Different numbers of cycles and steam temperatures were compared for efficacy in removing scale from lemons or killing those that remained. Multiple (two to three) cycles removed up to 96% of first molt scales on the fruit, but they were much less effective in removing other stages, especially those that had advanced beyond the second instar. However, it was extremely effective in killing the scales remaining on the fruit. Although this process does not eliminate cosmetic damage caused by scale presence, it might be used in combination with high-pressure washers currently used in packing houses to allow importers and exporters to meet the most stringent quarantine requirements. Because of its killing power, this technique should be tried on other insects and commodities to see whether it can be substituted for certain uses of methyl bromide.


Assuntos
Citrus , Frutas , Hemípteros , Controle de Insetos/métodos , Animais , Hidrocarbonetos Bromados , Vapor , Vácuo
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