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1.
Nat Commun ; 11(1): 4410, 2020 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-32879310

RESUMO

The hypothalamic suprachiasmatic (SCN) clock contains several neurochemically defined cell groups that contribute to the genesis of circadian rhythms. Using cell-specific and genetically targeted approaches we have confirmed an indispensable role for vasoactive intestinal polypeptide-expressing SCN (SCNVIP) neurons, including their molecular clock, in generating the mammalian locomotor activity (LMA) circadian rhythm. Optogenetic-assisted circuit mapping revealed functional, di-synaptic connectivity between SCNVIP neurons and dorsomedial hypothalamic neurons, providing a circuit substrate by which SCNVIP neurons may regulate LMA rhythms. In vivo photometry revealed that while SCNVIP neurons are acutely responsive to light, their activity is otherwise behavioral state invariant. Single-nuclei RNA-sequencing revealed that SCNVIP neurons comprise two transcriptionally distinct subtypes, including putative pacemaker and non-pacemaker populations. Altogether, our work establishes necessity of SCNVIP neurons for the LMA circadian rhythm, elucidates organization of circadian outflow from and modulatory input to SCNVIP cells, and demonstrates a subpopulation-level molecular heterogeneity that suggests distinct functions for specific SCNVIP subtypes.


Assuntos
Ritmo Circadiano/fisiologia , Neurônios/metabolismo , Núcleo Supraquiasmático , Animais , Mapeamento Encefálico , Relógios Circadianos/fisiologia , Locomoção/fisiologia , Camundongos , Optogenética/métodos , Núcleo Supraquiasmático/citologia , Núcleo Supraquiasmático/metabolismo
2.
Nat Commun ; 11(1): 4448, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895370

RESUMO

Substance abuse disorders are linked to alteration of circadian rhythms, although the molecular and neuronal pathways implicated have not been fully elucidated. Addictive drugs, such as cocaine, induce a rapid increase of dopamine levels in the brain. Here, we show that acute administration of cocaine triggers reprogramming in circadian gene expression in the striatum, an area involved in psychomotor and rewarding effects of drugs. This process involves the activation of peroxisome protein activator receptor gamma (PPARγ), a nuclear receptor involved in inflammatory responses. PPARγ reprogramming is altered in mice with cell-specific ablation of the dopamine D2 receptor (D2R) in the striatal medium spiny neurons (MSNs) (iMSN-D2RKO). Administration of a specific PPARγ agonist in iMSN-D2RKO mice elicits substantial rescue of cocaine-dependent control of circadian genes. These findings have potential implications for development of strategies to treat substance abuse disorders.


Assuntos
Relógios Circadianos/efeitos dos fármacos , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Cocaína/efeitos adversos , Núcleo Accumbens/efeitos dos fármacos , PPAR gama/metabolismo , Receptores de Dopamina D2/metabolismo , Administração Oral , Animais , Relógios Circadianos/fisiologia , Cocaína/administração & dosagem , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Dopamina/metabolismo , Injeções Intraperitoneais , Locomoção/fisiologia , Masculino , Camundongos , Camundongos Knockout , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Núcleo Accumbens/fisiopatologia , PPAR gama/agonistas , Pioglitazona/administração & dosagem , Receptores de Dopamina D2/genética , Recompensa , Transdução de Sinais
3.
Nat Commun ; 11(1): 4496, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32901024

RESUMO

Aging is characterized by the loss of homeostasis and the general decline of physiological functions, accompanied by various degenerative diseases and increased rates of mortality. Aging targeting small molecule screens have been performed many times, however, few have focused on endogenous metabolic intermediates-metabolites. Here, using C. elegans lifespan assays, we conducted a worm metabolite screen and identified an eukaryotes conserved metabolite, myo-inositol (MI), to extend lifespan, increase mobility and reduce fat content. Genetic analysis of enzymes in MI metabolic pathway suggest that MI alleviates aging through its derivative PI(4,5)P2. MI and PI(4,5)P2 are precursors of PI(3,4,5)P3, which is negatively related to longevity. The longevity effect of MI is dependent on the tumor suppressor gene, daf-18 (homologous to mouse Pten), independent of its classical pathway downstream genes, akt or daf-16. Furthermore, we found MI effects on aging and lifespan act through mitophagy regulator PTEN induced kinase-1 (pink-1) and mitophagy. MI's anti-aging effect is also conserved in mouse, indicating a conserved mechanism in mammals.


Assuntos
Envelhecimento/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Inositol/metabolismo , Longevidade/fisiologia , PTEN Fosfo-Hidrolase/metabolismo , Envelhecimento/efeitos dos fármacos , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Linhagem Celular Tumoral , Feminino , Fatores de Transcrição Forkhead/genética , Inositol/administração & dosagem , Locomoção/fisiologia , Longevidade/efeitos dos fármacos , Redes e Vias Metabólicas/genética , Metabolômica , Camundongos , Mitofagia/fisiologia , Modelos Animais , Fosfatos de Fosfatidilinositol/metabolismo , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Interferência de RNA , RNA-Seq
4.
Nat Commun ; 11(1): 4491, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32901033

RESUMO

The functionality of the nervous system requires transmission of information along axons with high speed and precision. Conductance velocity depends on axonal diameter whereas signaling precision requires a block of electrical crosstalk between axons, known as ephaptic coupling. Here, we use the peripheral nervous system of Drosophila larvae to determine how glia regulates axonal properties. We show that wrapping glial differentiation depends on gap junctions and FGF-signaling. Abnormal glial differentiation affects axonal diameter and conductance velocity and causes mild behavioral phenotypes that can be rescued by a sphingosine-rich diet. Ablation of wrapping glia does not further impair axonal diameter and conductance velocity but causes a prominent locomotion phenotype that cannot be rescued by sphingosine. Moreover, optogenetically evoked locomotor patterns do not depend on conductance speed but require the presence of wrapping glial processes. In conclusion, our data indicate that wrapping glia modulates both speed and precision of neuronal signaling.


Assuntos
Drosophila melanogaster/fisiologia , Animais , Animais Geneticamente Modificados , Axônios/fisiologia , Diferenciação Celular , Proteínas de Drosophila/genética , Proteínas de Drosophila/fisiologia , Drosophila melanogaster/citologia , Drosophila melanogaster/genética , Larva/citologia , Larva/fisiologia , Locomoção/fisiologia , Modelos Neurológicos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/fisiologia , Neuroglia/citologia , Neuroglia/fisiologia , Optogenética , Sistema Nervoso Periférico/citologia , Sistema Nervoso Periférico/fisiologia , Fenótipo , Receptores de Fatores de Crescimento de Fibroblastos/fisiologia , Transdução de Sinais
5.
Nat Commun ; 11(1): 4356, 2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32868777

RESUMO

Complex motor commands for human locomotion are generated through the combination of motor modules representable as muscle synergies. Recent data have argued that muscle synergies are inborn or determined early in life, but development of the neuro-musculoskeletal system and acquisition of new skills may demand fine-tuning or reshaping of the early synergies. We seek to understand how locomotor synergies change during development and training by studying the synergies for running in preschoolers and diverse adults from sedentary subjects to elite marathoners, totaling 63 subjects assessed over 100 sessions. During development, synergies are fractionated into units with fewer muscles. As adults train to run, specific synergies coalesce to become merged synergies. Presences of specific synergy-merging patterns correlate with enhanced or reduced running efficiency. Fractionation and merging of muscle synergies may be a mechanism for modifying early motor modules (Nature) to accommodate the changing limb biomechanics and influences from sensorimotor training (Nurture).


Assuntos
Músculo Esquelético/fisiologia , Corrida/fisiologia , Adulto , Fenômenos Biomecânicos , Criança , Pré-Escolar , Eletromiografia , Feminino , Humanos , Locomoção , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/crescimento & desenvolvimento
6.
PLoS One ; 15(8): e0237636, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32813715

RESUMO

We report the discovery of two very early, basal-amniote fossil trackways on the same bedding plane in eolian sandstone of the Pennsylvanian Manakacha Formation in Grand Canyon, Arizona. Trackway 1, which is Chelichnus-like, we interpret to be a shallow undertrackway. It displays a distinctive, sideways-drifting, footprint pattern not previously documented in a tetrapod trackway. We interpret this pattern to record the trackmaker employing a lateral-sequence gait while diagonally ascending a slope of about 20°, thereby reducing the steepness of the ascent. Trackway 2 consists only of aligned sets of claw marks. We interpret this trackway to be a deeper undertrackway, made some hours or days later, possibly by an animal that was conspecific with Trackmaker 1, while walking directly up the slope at a speed of approximately 0.1 m/sec. These trackways are the first tetrapod tracks reported from the Manakacha Formation and the oldest in the Grand Canyon region. The narrow width of both trackways indicates that both trackmakers had relatively small femoral abduction angles and correspondingly relatively erect postures. They represent the earliest known occurrence of dunefield-dwelling amniotes-either basal reptiles or basal synapsids-thereby extending the known utilization of the desert biome by amniotes, as well as the presence of the Chelichnus ichnofacies, by at least eight million years, into the Atokan/Moscovian Age of the Pennsylvanian Epoch. The depositional setting was a coastal-plain, eolian dunefield in which tidal or wadi flooding episodically interrupted eolian processes and buried the dunes in mud.


Assuntos
Adaptação Fisiológica , Marcha/fisiologia , Paleontologia/métodos , Vertebrados/fisiologia , Caminhada , Animais , Arizona , Meio Ambiente , Fósseis , Locomoção , Modelos Biológicos , Vertebrados/classificação
7.
PLoS One ; 15(8): e0237331, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822398

RESUMO

Speed skating is a technical endurance sport. Still, little is known about technical changes in junior speed skaters. Therefore, changes in technique throughout a 1500-m time-trial of elite junior speed skaters is investigated to explore differences between sexes, performance levels and competitive seasons. At (inter)national 1500-m competitions, knee and push-off angles were obtained for 120 elite junior speed skaters (56 female, 64 male, age 17.6±1.1 years) per lap at 250m (lap 1), 650m (lap 2), 1050m (lap 3) and 1450m (lap 4). Additionally, 1500m end-times and lap-times were obtained to divide skaters in faster and slower performance groups and to analyze pacing behavior. Fifteen skaters (8 female, 7 male, age 17.3±1.5 years) were measured again after 1.6±0.6 years. (Repeated measures) ANOVAs were used for statistical analyses (p<0.05). ICC, determined in a pilot study, was 0.55 for knee and 0.76 for push-off angles. Elite junior speed skaters increased their knee angles throughout the race (p<0.005), regardless of sex (p = 0.110) or performance level (p = 0.714). Push-off angles increased from lap 1-3 (p<0.001), in which men showed a larger decay than female skaters (p<0.05), this holds for both performance groups (p = 0.103). Faster skaters had smaller knee and push-off angles than slower skaters (p<0.05). Males showed smaller body angles than females (p<0.001). Faster male and female skaters showed a relative slower start and faster lap 3 compared to slower skaters (p<0.05). Development over competitive seasons showed a shift towards smaller push-off angles (p = 0.038) and less decay in knee angles from lap 2-3 (p = 0.026). The present study shows that technique throughout the 1500m deteriorates. Deterioration in technique is regardless of performance level, even with different pacing behaviors. Differences between sexes were found for push-off angles. The longitudinal development suggests changes in technique towards senior level and highlights the importance of studying juniors separate from seniors.


Assuntos
Atletas/estatística & dados numéricos , Desempenho Atlético/fisiologia , Locomoção/fisiologia , Patinação/fisiologia , Adolescente , Fatores Etários , Desempenho Atlético/estatística & dados numéricos , Desempenho Atlético/tendências , Feminino , Humanos , Articulação do Joelho/fisiologia , Masculino , Países Baixos , Projetos Piloto , Fatores Sexuais , Patinação/estatística & dados numéricos , Patinação/tendências , Fatores de Tempo
8.
PLoS One ; 15(8): e0231996, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32857774

RESUMO

Lower-limb wearable robotic devices can improve clinical gait and reduce energetic demand in healthy populations. To help enable real-world use, we sought to examine how assistance should be applied in variable gait conditions and suggest an approach derived from knowledge of human locomotion mechanics to establish a 'roadmap' for wearable robot design. We characterized the changes in joint mechanics during walking and running across a range of incline/decline grades and then provide an analysis that informs the development of lower-limb exoskeletons capable of operating across a range of mechanical demands. We hypothesized that the distribution of limb-joint positive mechanical power would shift to the hip for incline walking and running and that the distribution of limb-joint negative mechanical power would shift to the knee for decline walking and running. Eight subjects (6M,2F) completed five walking (1.25 m s-1) trials at -8.53°, -5.71°, 0°, 5.71°, and 8.53° grade and five running (2.25 m s-1) trials at -5.71°, -2.86°, 0°, 2.86°, and 5.71° grade on a treadmill. We calculated time-varying joint moment and power output for the ankle, knee, and hip. For each gait, we examined how individual limb-joints contributed to total limb positive, negative and net power across grades. For both walking and running, changes in grade caused a redistribution of joint mechanical power generation and absorption. From level to incline walking, the ankle's contribution to limb positive power decreased from 44% on the level to 28% at 8.53° uphill grade (p < 0.0001) while the hip's contribution increased from 27% to 52% (p < 0.0001). In running, regardless of the surface gradient, the ankle was consistently the dominant source of lower-limb positive mechanical power (47-55%). In the context of our results, we outline three distinct use-modes that could be emphasized in future lower-limb exoskeleton designs 1) Energy injection: adding positive work into the gait cycle, 2) Energy extraction: removing negative work from the gait cycle, and 3) Energy transfer: extracting energy in one gait phase and then injecting it in another phase (i.e., regenerative braking).


Assuntos
Análise da Marcha/métodos , Marcha/fisiologia , Robótica/instrumentação , Adulto , Tornozelo/fisiologia , Articulação do Tornozelo/fisiologia , Fenômenos Biomecânicos , Exoesqueleto Energizado/tendências , Feminino , Quadril/fisiologia , Articulação do Quadril/fisiologia , Humanos , Joelho/fisiologia , Articulação do Joelho/fisiologia , Locomoção , Extremidade Inferior/fisiologia , Masculino , Músculo Esquelético/fisiologia , Corrida/fisiologia , Caminhada/fisiologia
9.
Nat Commun ; 11(1): 3996, 2020 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-32778725

RESUMO

Psychomotor stimulants increase dopamine levels in the striatum and promote locomotion; however, their effects on striatal pathway function in vivo remain unclear. One model that has been proposed to account for these motor effects suggests that stimulants drive hyperactivity via activation and inhibition of direct and indirect pathway striatal neurons, respectively. Although this hypothesis is consistent with the cellular actions of dopamine receptors and received support from optogenetic and chemogenetic studies, it has been rarely tested with in vivo recordings. Here, we test this model and observe that cocaine increases the activity of both pathways in the striatum of awake mice. These changes are linked to a dopamine-dependent cocaine-induced strengthening of upstream orbitofrontal cortex (OFC) inputs to the dorsomedial striatum (DMS) in vivo. Finally, depressing OFC-DMS pathway with a high frequency stimulation protocol in awake mice over-powers the cocaine-induced potentiation of OFC-DMS pathway and attenuates the expression of locomotor sensitization, directly linking OFC-DMS potentiation to cocaine-induced hyperactivity.


Assuntos
Estimulantes do Sistema Nervoso Central/farmacologia , Cocaína/farmacologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Hipercinese/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Animais , Comportamento Animal , Modelos Animais de Doenças , Dopamina , Feminino , Hipercinese/induzido quimicamente , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Optogenética
10.
Nat Commun ; 11(1): 4171, 2020 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-32820176

RESUMO

Spiralia is a large, ancient and diverse clade of animals, with a conserved early developmental program but diverse larval and adult morphologies. One trait shared by many spiralians is the presence of ciliary bands used for locomotion and feeding. To learn more about spiralian-specific traits we have examined the expression of 20 genes with protein motifs that are strongly conserved within the Spiralia, but not detectable outside of it. Here, we show that two of these are specifically expressed in the main ciliary band of the mollusc Tritia (also known as Ilyanassa). Their expression patterns in representative species from five more spiralian phyla-the annelids, nemerteans, phoronids, brachiopods and rotifers-show that at least one of these, lophotrochin, has a conserved and specific role in particular ciliated structures, most consistently in ciliary bands. These results highlight the potential importance of lineage-specific genes or protein motifs for understanding traits shared across ancient lineages.


Assuntos
Motivos de Aminoácidos/genética , Cílios/genética , Invertebrados/genética , Proteínas/genética , Animais , Anelídeos/classificação , Anelídeos/genética , Anelídeos/fisiologia , Evolução Biológica , Cílios/fisiologia , Comportamento Alimentar/fisiologia , Perfilação da Expressão Gênica/métodos , Invertebrados/classificação , Invertebrados/fisiologia , Larva/genética , Larva/fisiologia , Locomoção/fisiologia , Moluscos/classificação , Moluscos/genética , Moluscos/fisiologia , Filogenia , Especificidade da Espécie
11.
Nat Commun ; 11(1): 3848, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737286

RESUMO

Amyotrophic Lateral Sclerosis (ALS) is a fatal disease characterized by the degeneration of upper and lower motor neurons (MNs). We find a significant reduction of the retromer complex subunit VPS35 in iPSCs-derived MNs from ALS patients, in MNs from ALS post mortem explants and in MNs from SOD1G93A mice. Being the retromer involved in trafficking of hydrolases, a pathological hallmark in ALS, we design, synthesize and characterize an array of retromer stabilizers based on bis-guanylhydrazones connected by a 1,3-phenyl ring linker. We select compound 2a as a potent and bioavailable interactor of VPS35-VPS29. Indeed, while increasing retromer stability in ALS mice, compound 2a attenuates locomotion impairment and increases MNs survival. Moreover, compound 2a increases VPS35 in iPSCs-derived MNs and shows brain bioavailability. Our results clearly suggest the retromer as a valuable druggable target in ALS.


Assuntos
Esclerose Amiotrófica Lateral/tratamento farmacológico , Hidrazonas/farmacologia , Neurônios Motores/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Proteínas de Transporte Vesicular/genética , Esclerose Amiotrófica Lateral/genética , Esclerose Amiotrófica Lateral/metabolismo , Esclerose Amiotrófica Lateral/patologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Diferenciação Celular , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Hidrazonas/síntese química , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/metabolismo , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Masculino , Camundongos , Camundongos Transgênicos , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/síntese química , Ligação Proteica/efeitos dos fármacos , Multimerização Proteica , Relação Estrutura-Atividade , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo , Proteínas de Transporte Vesicular/metabolismo
12.
Life Sci ; 258: 118099, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32682917

RESUMO

Although emerging evidence has highlighted the heterogeneities of astrocytes under physiological versus pathological conditions, little is known regarding these processes in different brain regions during stress. Thus, the present study established a mouse model of chronic social defeat stress (CSDS) and isolated astrocytes from the medial prefrontal cortex (mPFC) and hippocampus. The results revealed dramatic A1-specific (neurotoxic phenotype) astrocytic responses, depressive-like behaviors, and significant inhibition of neuronal activities in both the mPFC and hippocampus according to electrophysiological data. Subsequently, astrocytes in the mPFC and hippocampus of CSDS mice were suppressed and this reversed the astrocytic responses and rescued depressive-like behaviors. Furthermore, when astrocytes were activated in the mPFC and hippocampus in healthy mice, there was a non-specific phenotypic activation of astrocytes in the absence of depressive-like behaviors. Next, microglia were depleted and the mice subsequently performed in the CSDS model; this reduced astrocyte responses and restored depressive-like behaviors. On the other hand, when microglia were depleted but astrocytes were activated in CSDS mice, this abolished the restoration of microglia depletion-induced depressive-like behaviors. Taken together, these results indicate that neuronal inhibition by astrocytes in the mPFC and hippocampus contributed to depressive-like behaviors mediated by activated microglia. This study provides evidence regarding the interaction of microglia and astrocytes during stress and how that relationship can trigger depressive-like behaviors.


Assuntos
Astrócitos/patologia , Comportamento Animal , Depressão/psicologia , Neurônios/patologia , Estresse Psicológico/patologia , Animais , Doença Crônica , Hipocampo/patologia , Locomoção , Masculino , Camundongos , Inibição Neural , Neuroglia/metabolismo , Córtex Pré-Frontal/patologia
13.
Chemosphere ; 260: 127627, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32673864

RESUMO

Nickel is the most prevailing metal allergen with the highest sensitization rate among the "TOP 25" contact allergens and can affect about 15% of the human population. It is an essential trace metal in plants, animals, and humans. However, the environmental levels of nickel are considerably higher than what is needed for human life. Exposure to high levels of nickel can lead to skin allergies, lung fibrosis, and carcinogenesis. Few existing studies have closely examined the toxicity of nickel, let alone investigated the effective detoxification pathways. Here, we developed a high-throughput screening platform to comprehensively evaluate the nickel toxicity in wild-type C. elegans and explore the underlying detoxification mechanisms in transgenic nematodes. We demonstrated that nickel exerted multiple toxic effects on growth, brood size, feeding, and locomotion in C. elegans. Of which, brood size is the most sensitive endpoint. Nickel was found to first bind to phytochelatin (PC) after entering the worms' body and this PC-Ni complex was further transported by the ABC transporter, CeHMT-1, into the coelomocytes for further detoxification. Our study also demonstrated that the high-throughput screening platform is a promising system for evaluation and investigation of the ecological risks of heavy metals.


Assuntos
Caenorhabditis elegans/fisiologia , Níquel/metabolismo , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Transporte Biológico , Caenorhabditis elegans/metabolismo , Locomoção , Metais Pesados/toxicidade , Nematoides , Níquel/toxicidade , Fitoquelatinas/metabolismo
14.
Integr Comp Biol ; 60(1): 134-139, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32699901

RESUMO

Elongate, limbless body plans are widespread in nature and frequently converged upon (with over two dozen independent convergences in Squamates alone, and many outside of Squamata). Despite their lack of legs, these animals move effectively through a wide range of microhabitats, and have a particular advantage in cluttered or confined environments. This has elicited interest from multiple disciplines in many aspects of their movements, from how and when limbless morphologies evolve to the biomechanics and control of limbless locomotion within and across taxa to its replication in elongate robots. Increasingly powerful tools and technology enable more detailed examinations of limbless locomotor biomechanics, and improved phylogenies have shed increasing light on the origins and evolution of limblessness, as well as the high frequency of convergence. Advances in actuators and control are increasing the capability of "snakebots" to solve real-world problems (e.g., search and rescue), while biological data have proven to be a potent inspiration for improvements in snakebot control. This collection of research brings together prominent researchers on the topic from around the world, including biologists, physicists, and roboticists to offer new perspective on locomotor modes, musculoskeletal mechanisms, locomotor control, and the evolution and diversity of limbless locomotion.


Assuntos
Lagartos/fisiologia , Locomoção/fisiologia , Serpentes/fisiologia , Animais , Fenômenos Biomecânicos , Meio Ambiente
15.
Arq. ciências saúde UNIPAR ; 24(2): 113-116, maio-ago. 2020.
Artigo em Português | LILACS | ID: biblio-1116374

RESUMO

O estudo da Anatomia Humana (AH) é parte integrante e de relevância inquestionável na graduação dos cursos da saúde. Com a constante redução na carga horária destinada à AH e diante dos debates sobre os novos métodos de ensino, o uso do código de quick response (código QR) se mostrou promissor. Nesse sentido, foi desenvolvido no Departamento de Anatomia da Universidade Estadual de Londrina (UEL) o processo de catalogação das estruturas anatômicas com o uso do código QR, sendo nosso objetivo relatar esta experiência. Neste processo, as estruturas dissecadas no Laboratório de Anatomia da UEL foram catalogadas com base em uma planilha contendo a correlação entre estruturas e números e, as informações de cada estrutura transcritas em um código QR através de um gerador eletrônico, sendo então impresso, plastificado e anexado à peça anatômica. As marcações foram realizadas por meio da sutura de etiquetas enumeradas. Dentro da discussão dos métodos alternativos de ensino há como exemplos a plastinação, a projeção em três dimensões e a prospecção. Em destaque neste relato, o uso do código QR mostrou-se como uma alternativa válida na agregação de conhecimento nos currículos acadêmicos. Por meio das atividades empreendidas no processo de catalogação, foi possível, além da aquisição de mais tempo dedicado ao conhecimento teórico-prático em AH, ampliar a independência no estudo e no desenvolvimento de pesquisas. Dessa forma, tem-se a oportunidade de se expandir as análises voltadas ao ensino da AH e aos novos métodos de aprendizado.


The study of human anatomy is a relevant part of the curriculum of health course graduation students. Given the constant reduction of hours destinated to the study of Anatomy and the debates regarding new teaching methods, the use of the Quick Response Code (QR code) has shown to be promising. Therefore, the Anatomy Department at the State University of Londrina (UEL) has developed a cataloging process concerning anatomical structures with the application of QR code, and this paper has the purpose of reporting on such experience. In the process, the structures dissected in UEL's Anatomy Laboratory were cataloged based on a spreadsheet which contained the correlation between these structures and numbers; the information regarding each structure was then transcribed into a QR code using a digital generator, with posterior printing, lamination and attachment to the body part. The labels were made by sewing the numbered tags onto the structures. Within the discussion regarding alternative teaching methods, examples can be given regarding lamination, three-dimension projection and prospection. The use of the QR code has proven to be a valid alternative in aggregating knowledge to academic curriculum. Through the activities performed in the process of cataloging, it was possible not only to dedicate more time to the theorical and practical learning of human anatomy, but also to increase the independence in studying and developing research. Furthermore, there is an opportunity to expand the analysis directed toward human anatomy teaching and toward new learning methods.


Assuntos
Educação em Saúde/classificação , Tecnologia Educacional/instrumentação , Educação de Graduação em Medicina/métodos , Anatomia/classificação , Aprendizagem/classificação , Locomoção/fisiologia , Estudantes de Medicina/classificação , Universidades/organização & administração , Catalogação/estatística & dados numéricos , Corpo Humano , Currículo/normas , Educação Superior , Fenômenos Fisiológicos Musculoesqueléticos
16.
Braz J Med Biol Res ; 53(8): e10034, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32609258

RESUMO

Contradictory findings suggest that the behavioral and abuse-related effects of ethanol are mediated by its action at α1 subunit-containing GABAA (α1GABAA) receptors. In the present study, we investigated the effects of a sub-chronic post-ethanol administration treatment with zolpidem, an α1-preferring positive allosteric modulator at GABAA receptors, on the subsequent expression of ethanol-induced behavioral sensitization in mice. Animals received ethanol (1.8 g/kg, ip) or saline treatments every other day for 15 days (8 treatment sessions) and were subsequently treated with zolpidem (0.5 mg/kg, ip) or vehicle 4 times on alternate days. At the end of the treatment phase, animals were challenged with saline or ethanol on separate days for the evaluation of the expression of conditioned locomotion and behavioral sensitization. Eight-day treatment with ethanol did not lead to the development of ethanol-induced behavioral sensitization. Animals treated with ethanol and subsequently administered vehicle showed similar locomotion frequencies during the last ethanol challenge compared to the control group receiving ethanol for the first time. Animals treated with ethanol and subsequently administered zolpidem expressed behavioral sensitization to ethanol during the ethanol challenge. The present study adds to the literature by providing further evidence of a role of α1GABAA receptors on the behavioral effects of ethanol. Because of the current highly prevalent co-abuse of ethanol and benzodiazepine drugs in humans, the use of zolpidem and other α1GABAA receptor ligands during ethanol withdrawal should be monitored carefully.


Assuntos
Etanol , Agonistas de Receptores de GABA-A/farmacologia , Zolpidem/farmacologia , Animais , Benzodiazepinas , Locomoção , Masculino , Camundongos , Receptores de GABA-A
18.
PLoS One ; 15(7): e0235702, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32634159

RESUMO

Rheumatoid arthritis (RA) is accompanied by pain, inflammation and muscle weakness. Skeletal muscle inflammation and inactivity are independently associated with muscle insulin resistance and atrophy. Our objective was to identify early molecular and biochemical markers in muscle from a rodent model of RA relative to control and subsequently identify commonality in muscle gene expression between this model and muscle from RA patients. Pain behaviour and locomotor activity were measured in a collagen-induced arthritis (CIA) model of RA (n = 9) and control (n = 9) rats. Energy substrates and metabolites, total alkaline-soluble protein:DNA ratio and mRNA abundance of 46 targeted genes were also determined in Extensor digitorum longus muscle. Expression of targeted mRNAs was quantified in Vastus Lateralis muscle from RA patients (n = 7) and healthy age-matched control volunteers (n = 6). CIA rats exhibited pain behaviour (p<0.01) and reduced activity (p<0.05) compared to controls. Muscle glycogen content was less (p<0.05) and muscle lactate content greater (p<0.01) in CIA rats. The bioinformatics analysis of muscle mRNA abundance differences from the control, predicted the activation of muscle protein metabolism and inhibition of muscle carbohydrate and fatty acid metabolism in CIA rats. Compared to age-matched control volunteers, RA patients exhibited altered muscle mRNA expression of 8 of the transcripts included as targets in the CIA model of RA. In conclusion, muscle energy metabolism and metabolic gene expression were altered in the CIA model, which was partly corroborated by targeted muscle mRNA measurements in RA patients. This research highlights the negative impact of RA on skeletal muscle metabolic homeostasis.


Assuntos
Artrite Reumatoide/complicações , Músculo Esquelético/metabolismo , Doenças Musculares/etiologia , Idoso , Animais , Artrite Experimental/metabolismo , Artrite Reumatoide/metabolismo , Biomarcadores , Modelos Animais de Doenças , Feminino , Glicogênio/metabolismo , Humanos , Inflamação , Locomoção , Pessoa de Meia-Idade , Doenças Musculares/metabolismo , Mialgia/etiologia , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos Lew , Transcriptoma
19.
Nature ; 583(7816): 421-424, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32641825

RESUMO

The suprachiasmatic nucleus (SCN) serves as the body's master circadian clock that adaptively coordinates changes in physiology and behaviour in anticipation of changing requirements throughout the 24-h day-night cycle1-4. For example, the SCN opposes overnight adipsia by driving water intake before sleep5,6, and by driving the secretion of anti-diuretic hormone7,8 and lowering body temperature9,10 to reduce water loss during sleep11. These responses can also be driven by central osmo-sodium sensors to oppose an unscheduled rise in osmolality during the active phase12-16. However, it is unknown whether osmo-sodium sensors require clock-output networks to drive homeostatic responses. Here we show that a systemic salt injection (hypertonic saline) given at Zeitgeber time 19-a time at which SCNVP (vasopressin) neurons are inactive-excited SCNVP neurons and decreased non-shivering thermogenesis (NST) and body temperature. The effects of hypertonic saline on NST and body temperature were prevented by chemogenetic inhibition of SCNVP neurons and mimicked by optogenetic stimulation of SCNVP neurons in vivo. Combined anatomical and electrophysiological experiments revealed that osmo-sodium-sensing organum vasculosum lamina terminalis (OVLT) neurons expressing glutamic acid decarboxylase (OVLTGAD) relay this information to SCNVP neurons via an excitatory effect of γ-aminobutyric acid (GABA). Optogenetic activation of OVLTGAD neuron axon terminals excited SCNVP neurons in vitro and mimicked the effects of hypertonic saline on NST and body temperature in vivo. Furthermore, chemogenetic inhibition of OVLTGAD neurons blunted the effects of systemic hypertonic saline on NST and body temperature. Finally, we show that hypertonic saline significantly phase-advanced the circadian locomotor activity onset of mice. This effect was mimicked by optogenetic activation of the OVLTGAD→ SCNVP pathway and was prevented by chemogenetic inhibition of OVLTGAD neurons. Collectively, our findings provide demonstration that clock time can be regulated by non-photic physiologically relevant cues, and that such cues can drive unscheduled homeostatic responses via clock-output networks.


Assuntos
Relógios Circadianos/fisiologia , Vias Neurais , Neurônios/metabolismo , Sódio/metabolismo , Núcleo Supraquiasmático/fisiologia , Ácido gama-Aminobutírico/metabolismo , Animais , Temperatura Corporal/efeitos dos fármacos , Temperatura Corporal/fisiologia , Relógios Circadianos/efeitos dos fármacos , Ritmo Circadiano/efeitos dos fármacos , Ritmo Circadiano/fisiologia , Ingestão de Líquidos/efeitos dos fármacos , Glutamato Descarboxilase/metabolismo , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Masculino , Camundongos , Vias Neurais/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Optogenética , Organum Vasculosum/citologia , Organum Vasculosum/efeitos dos fármacos , Organum Vasculosum/enzimologia , Organum Vasculosum/fisiologia , Concentração Osmolar , Solução Salina Hipertônica/administração & dosagem , Solução Salina Hipertônica/metabolismo , Solução Salina Hipertônica/farmacologia , Sódio/administração & dosagem , Sódio/farmacologia , Núcleo Supraquiasmático/citologia , Núcleo Supraquiasmático/efeitos dos fármacos , Vasopressinas/metabolismo
20.
PLoS Biol ; 18(7): e3000712, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32663220

RESUMO

Tools enabling closed-loop experiments are crucial to delineate causal relationships between the activity of genetically labeled neurons and specific behaviors. We developed the Raspberry Pi Virtual Reality (PiVR) system to conduct closed-loop optogenetic stimulation of neural functions in unrestrained animals. PiVR is an experimental platform that operates at high temporal resolution (70 Hz) with low latencies (<30 milliseconds), while being affordable (

Assuntos
Comportamento Animal/fisiologia , Drosophila melanogaster/fisiologia , Optogenética , Córtex Sensório-Motor/fisiologia , Realidade Virtual , Animais , Quimiotaxia , Larva/fisiologia , Luz , Locomoção , Masculino , Neurônios/fisiologia , Odorantes , Sensação/fisiologia , Software , Paladar/fisiologia , Peixe-Zebra
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